Clinical Trials Resource Center

New Medical Therapies™

Ovarian Cancer

August 12, 2013

GlaxoSmithKline issued results of a randomized, double-blind, phase III, placebo controlled trial of pazopanib monotherapy in women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had not progressed after completing standard debulking surgery and first-line chemotherapy. After completion of five or more cycles of platinum-taxane chemotherapy, 940 patients were randomized 1:1 to receive 800mg pazopanib once daily or placebo for up to 24 months (median time from diagnosis to randomization was approximately seven months). Pazopanib treatment reduced the risk of disease progression or death by 23% (HR = 0.77; 95% CI: 0.64-0.91; p = 0.0021). The incidence of serious adverse events was higher in the pazopanib group compared to the placebo group (26% v. 11%). Regulatory applications will be submitted before 2014.

July 1, 2013

Amgen reported results from a phase III trial of trebananib plus paclitaxel v. placebo plus paclitaxel for the treatment of recurrent ovarian cancer. This global, multicenter, randomized, double-blind, placebo-controlled study enrolled 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15mg/kg of intravenous trebananib weekly plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off). The trial met its primary endpoint of progression-free survival (PFS). A statistically significant difference was observed in PFS with a 34% reduction in the risk of disease progression or death (HR = 0.66, 95% CI, 0.57, 0.77, p<0.001). The median PFS was 7.2 months in the trebananib arm v. 5.4 months in the control arm.

August 8, 2011

Oasmia released interim data from a comparative phase III trial of paclical for ovarian cancer. The trial was designed to compare the pharmacokinetics and efficacy of 250mg/m2 of paclical with 175 mg/m2 of Taxol, the current standard of care, each in combination with carboplatin for six cycles followed by a six-month follow-up period. The interim analysis was performed by calculating the levels of CA 125, a measure used to evaluate treatment response and progression of ovarian cancer. Data from 400 subjects demonstrated that Paclical reduced CA 125 to the same level as Taxol.

June 13, 2011

Endocyte issued results from a phase IIb trial of EC145 for the treatment of platinum-resistant ovarian cancer. This randomized, open label trial, dubbed PRECEDENT, enrolled 149 women who received the combination of EC145 and Pegylated Liposomal Doxorubicin (PLD) or PLD alone until disease progression or death. The primary endpoint was progression free survival (PFS). The median PFS for the entire population, regardless of folate receptor expression, was five months in the EC145/PLD arm compared to 2.7 months for the PLD single agent arm (p≡0.031). The overall response rate was 28% in the EC145 combination group versus 16% in the PLD-alone group. The study also utilized EC20, an investigational companion imaging diagnostic designed to identify subjects with folate receptor positive tumors. In the subgroup identified as most positive for the folate receptor, PFS increased by four months, from 1.5 months to 5.5 months (p≡.018), representing more than a 60% reduction in the risk of progression. The overall response rate was 22% in the EC145 combination group versus 7% in the PLD-alone group.

February 14, 2011

Genentech issued preliminary results from a phase III trial of Avastin for ovarian cancer. This randomized, double-blind, placebo-controlled trial, OCEANS, enrolled 484 subjects with platinum-sensitive recurrent ovarian, primary peritoneal or fallopian tube cancer. The subjects received Avastin (15 mg/kg every three weeks) or placebo in combination with carboplatin and gemcitabine chemotherapy, followed by Avastin or placebo as a single agent until disease progression. The study showed that the subjects who received a combination of Avastin and chemotherapy, followed by the continued use of Avastin alone, lived longer without their disease worsening (progression-free survival), compared to those who received chemotherapy alone.

November 22, 2010

Exelixis issued positive interim results from a phase II trial of XL184 for the treatment of advanced solid tumors. Data are from 51 subjects with ovarian cancer who received XL184 administered orally at a daily dose of 100 mg. Of the 51 subjects, 31 were evaluable for response, and 41 were evaluable for safety. Tumor shrinkage was observed in 30 of 37 (81%) subjects with measurable metastatic lesions. Of 31 subjects evaluable for response per RECIST, 10 (32%) achieved a confirmed partial response (PR). Stable disease (SD) was reported in 15 subjects (48%), including three who achieved unconfirmed PRs. The overall week-12 disease control rate (DCR) was 64%. In a subset analysis of platinum-refractory or -resistant patients, 5 of 17 (29%) evaluable for response per RECIST achieved a confirmed PR. SD was reported in 7 subjects (41%) including two with unconfirmed PRs. The week-12 DCR was 59% in this population. Durable responses were observed, including two subjects with platinum-refractory or resistant disease who remain on study for 34+ and 36+ weeks, and three subjects with platinum-sensitive disease on study for 24, 24+, and 28+ weeks.

October 18, 2010

Amgen reported positive results from a phase II trial of AMG 386 for the treatment of ovarian cancer. This trial enrolled 161 female subjects who were randomized to receive paclitaxel weekly, three weeks on and one week off, plus weekly: AMG 386 at 10 mg/kg, AMG 386 at 3 mg/kg or placebo. The primary endpoint, median progression-free survival, was reached. The median progression-free survival in the 10 mg/kg arm was 7.3 months, versus 7.4 months in the 3 mg/kg arm and 5.0 months in the placebo group (P≡0.022 for both AMG386 arms vs. placebo).Overall survival in the 10 mg/kg arm was 22.5 months (P≡.081) versus 20.4 months in the 3 mg/kg arm (P≡.330) and 20.9 months in the placebo group. The objective response rate, per RECIST, was 37% in the 10 mg/kg arm versus 21% in the 3 mg/kg arm and 27% in the placebo group.

July 12, 2010

Genentech issued positive preliminary results from a phase III trial of Avastin for ovarian cancer. This international, multicenter, randomized, open-label study, ICON7, enrolled 1,528 female subjects with previously untreated epithelial ovarian, primary peritoneal or fallopian tube carcinoma. The subjects were randomized to Arm 1: chemotherapy (carboplatin and paclitaxel) for six cycles or Arm 2: Avastin (7.5mg/kg every three weeks) in combination with chemotherapy (carboplatin and paclitaxel) for six cycles followed by Avastin alone (for a total of 18 cycles, up to 12 months). The primary endpoint, progression free survival, was increased in the subjects receiving Avastin plus chemotherapy compared those receiving chemotherapy alone. There were no unexpected adverse events.

March 1, 2010

Genentech issued positive initial results from a phase III trial of Avastin for the treatment of ovarian cancer. This international, randomized, double-blind, placebo-controlled study, GOG 0218, enrolled 1,873 female subjects with previously untreated advanced epithelial ovarian, primary peritoneal or fallopian tube cancer. The subjects were placed into one of three arms: Arm 1: placebo in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for up to 15 months of therapy; Arm 2: Avastin in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for up to 15 months of therapy and Arm 3: Avastin in combination with carboplatin and paclitaxel chemotherapy followed by the maintenance use of Avastin alone, for up to 15 months of therapy. The primary endpoint was progression free survival between the three arms. The study showed that the subjects who continued maintenance use of Avastin alone, after receiving Avastin in combination with chemotherapy (Arm 3), lived longer without worsening of disease compared to those who received chemotherapy alone. The subjects in Arm 2 did not live longer without the disease worsening compared to chemotherapy alone.

January 18, 2010

Nektar reported positive preliminary results from a phase II trial of NKTR-102 for the treatment of ovarian cancer. This open label, single arm two-stage study has enrolled 40 female subjects with platinum-resistant ovarian cancer. The subjects received NKTR-102 every 14 days (q14) or every 21 days (q21). Of the 40 enrolled subjects, 39 were evaluable for the primary endpoint of overall response rate using Gynecologic Cancer InterGroup (GCIG) criteria. The overall GCIG response rate was 32% in the q14 dose schedule and 35% in the q21 dose schedule. Confirmed objective response rates using RECIST were 21% and 22% for the q14 day and q21 day dose schedules, respectively. The response rates for CA-125, a cancer biomarker, were 31% and 38% for each dose schedule, respectively.

September 22, 2008

PharmaMar reported positive results from a phase III trial of Yondelis for the treatment of ovarian cancer. This randomized study enrolled 627 women with ovarian cancer who had relapsed after receiving standard first-line chemotherapy, across several international sites. The subjects received Yondelis in combination with Doxil (pegylated liposomal doxorubicin) or Doxil alone. The primary endpoint, progression-free survival, was reached with statistical significance. Median progression-free survival was 7.3 months for subjects who received the combination of Yondelis and Doxil versus 5.8 months for those treated with Doxil alone (p=0.019), for a clinically meaningful 21% reduction in the risk of progression or death. There was an increased response rate with the Yondelis and Doxil combination of 28% versus Doxil alone (19%), as measured by a blinded radiology review. The secondary endpoint of overall survival has not been determined, however a positive trend with a 15% reduction in the risk of death favored the Yondelis and Doxil treatment group. Treatment was generally well tolerated. Based on the results, PharmaMar and plans to file an MAA with the EMEA and, with their U.S partner, an NDA with the FDA, both before the end of 2008.

December 10, 2007

United Therapeutics issued negative preliminary results from two phase III trials of OvaRex for the treatment of ovarian cancer. These randomized, double-blind, placebo-controlled studies, dubbed IMPACT I and II, enrolled 367 subjects in the United States. The trial was designed to compare the efficacy of OvaRex mono- immunotherapy following front- line carboplatin-paclitaxel based chemotherapy. The primary endpoint, time to disease relapse, failed to reach statistical significance. No differences between active (standard of care followed by OvaRex) and control (standard of care followed by placebo) populations were observed for the primary endpoint, safety or quality of life profiles. Based on the results, United Therapeutics plans to terminate the development of OvaRex.

October 29, 2007

Cephalon reported positive results from a phase III trial of Treanda for the treatment of non-Hodgkins lymphoma (NHL). This multicenter, single-arm study, conducted under a SPA from the FDA, enrolled 100 subjects with relapsed, rituximab-refractory NHL who were no longer responsive to treatment with rituximab. The primary endpoints, overall response rate and median duration of response, were both achieved. The overall response rate, including complete, unconfirmed complete or partial response, was reached by 75% (p<0.0001) and the median duration of response was 40 weeks (9.2 months). Treatment was determined to be safe and well tolerated. Based on the results, Cephalon plans to file a sNDA with the FDA in Q4 of 2007.

EntreMed issued positive results from a phase II trial of Panzem for the treatment of ovarian cancer. This open label trial enrolled 18 women with platinum refractory epithelial ovarian cancer who received Panzem administered as a single agent. One subject had confirmed partial response of their CA- 125, a tumor bio-marker. Five of the eighteen subjects achieved stable disease lasting greater than three months. Treatment was well tolerated, with no reports of significant neuropathy, myelosuppression or thromboembolic side effects. Two subjects remain in the study at this time. Based on the results, EntreMed plans to advance the development of Panzem for this indication.

Sunesis released positive preliminary results from an ongoing phase II trial of SNS-595 for the treatment of ovarian cancer. This trial enrolled 31 subjects to date, 15 of whom were evaluable at this time. The subjects received SNS-595 once every three weeks by intravenous infusion for up to eight cycles. Anti-tumor activity was observed, with 88% of the subjects showing stable disease or better, including two partial responses. Four of the subjects with measurable tumor shrinkage previously failed prior platinum-containing regimens and treatment with Doxil. Treatment was generally well tolerated. Sunesis plans to complete this trial and announce final results in 2008.

September 24, 2007

Exelexis announced positive interim results from a phase II trial of XL647 for the treatment of non-small cell lung cancer (NSCLC). Reported data is from 30 evaluable subjects with stage IIIB or IV NSCLC who received XL647 administered orally, at a dose of 350 mg on days 1-5 of repeated 14-day cycles. To date 8 partial responses and 11 stable disease had been reported. Of the 8 subjects who experienced partial responses, 4 had epidermal growth factor receptor (EGFR) exon 19 deletions, 1 had an EGFR L858R mutation, and 3 were EGFR wild-type. All 6 subjects with EGFR-activating mutations demonstrated clinical benefit, with 5 partial response and 1 stable disease. Treatment was generally well tolerated. Additional phase II trials are currently underway.

Kosan issued positive results from a phase I trial of alvespimycin for the treatment of breast and ovarian cancer. This trial enrolled 25 subjects who received one-hour weekly intravenous infusion of 60, 80 or 100 mg/m2 alvespimycin administered along with the standard dose of trastuzumab. The subjects were assessed every four weeks for toxicity and every eight weeks for response, as measured by RECIST criteria and tumor markers. Clinical benefit was observed in 42% of evaluable subjects with HER2-positive metastatic breast cancer. This included one subject with complete resolution of lung metastases, one subject with a 10% reduction in tumor mass and tumor necrosis, one subject with a partial response after 2 cycles and five subjects with stable disease. Of the subjects with ovarian cancer, there was one subject with a near complete resolution of ascites and left pleural effusion at the end of cycle 2. Based on the results, Kosan plans to expand the phase I trial to add weekly dosing with paclitaxel. Phase II trials are planned for Q4 of 2007.

Merck reported positive long-term results from a phase II trial of Stimuvax for the treatment of non-small cell lung cancer (NSCLC). This study enrolled 171 subjects with stage IIIB/IV nsclc with stable or responding disease after any first-line chemotherapy with or without radiotherapy. The subjects were stratified by disease stage than randomized to receive Stimuvax plus best supportive care (BSC) or BSC alone. The subjects in the Stimuvax arm received a single intravenous dose of cyclophosphamide 300mg/m2 followed by 8 weekly subcutaneous immunizations with Stimuvax (1,000 mg). Although the overall study results did not reach statistical significance, the subjects with stage IIIB cancer receiving Stimuvax showed a median survival of 30.6 months versus 13.3 months in the control group. At the three year follow-up, 49% of the subjects who were treated with Stimuvax were still alive versus 27% treated with BSC alone, representing a 45% reduction in mortality. Based on the results, Merck is currently conducting a phase III trial of Stimuvax for the treatment of stage IIIA or IIIB non-small cell lung cancer.

YM BioSciences announced positive preliminary results from a phase I/II trial of nimotuzumab for the treatment of non-small cell lung cancer (nsclc). This trial had enrolled 13 subjects to date in Canada. The subjects received nimotuzumab at three dose levels (100 mg, 200 mg and 400 mg weekly) with palliative radiation. Of the six subjects enrolled in the first cohort (100 mg), four partial response (PR) and two stable disease (SD) were reported. Median Overall Survival was 41.5 weeks. Of the seven subjects in the second cohort (200 mg) two PR and five SD were reported. Median Overall Survival in this group had not been reached but exceeded 25 weeks at this time. Treatment was generally well tolerated in both arms. Enrollment in the third cohort is underway, with accrual anticipated to be completed by the end of 2007. These results will be used to determine the optimal dose for the randomized phase II portion of the study.

March 19, 2007

PrimaBioMed released positive results from a phase IIa trial of Cancer Vacfor the treatment of ovarian cancer. This trial enrolled 28 subjects, 21 ofwhom were evaluable for response. The primary endpoint of the trial was todetermine if Cancer Vac would reduce or stabilize the blood marker CA125 in atleast 15% of the subjects. Clinical response or stable disease was seen in fourof the 21 subjects (19%; CI 5.4 - 41.9%). Two of the four subjects experienceda major response, as defined by a >50% reduction in CA125 levels, which wereconfirmed by two readings 21 days apart. One subject had major response for 44weeks and one for 42 weeks. One subject experienced a minor response, asdefined by a >25% reduction in CA125 levels, which were confirmed by tworeadings 21 days apart. This response lasted 10 weeks during a 34 week periodof disease stabilization. The fourth subject had stable disease, defined as +/-<25% change in CA125 that had to last at least 3 months, for 27 weeks. Based onthe results a phase IIb trial was planned for 2007.

October 23, 2006

Antisoma released positive results from a phase II trial of ASI1404 for the treatment of ovarian cancer. This trial enrolled 77 women with ovarian cancer that had recurred six months or more after treatment with platinum chemotherapy. Subjects were randomized to receive either AS1404 in combination with carboplatin and paclitaxel or carboplatin and paclitaxel alone. Treatment was well tolerated with no serious adverse events reported. Efficacy data revealed that of the subjects in the ASI1404 treatment group, 75.0% had a complete or partial response, 19.4% had stable disease and 5.6% had progressive disease, versus the control group at 63.2%, 28.9% and 7.9%, respectively. Based on the data Antisoma plans to begin development of phase III trials.

Wilex issued positive two year data from a phase II study of Rencarex, in combination with low dose Interferon alpha-2a, for the treatment of renal cell cancer (RCC). This trial enrolled 31 subjects with RCC who had the affected kidney removed. The median survival rate was 30 months and a 57% of the subjects had a two year survival rate. In addition, the subjects who were treated for an additional 6 weeks past the original 12 week treatment phase had a statistically significant survival benefit when compared to those subjects who stopped treatment at 12 weeks. The median survival for those on continuing therapy was 45 months with a 2-year survival rate of 79 % versus a median survival of 10 months with a 2-year survival rate of 30 %. Rencarex is currently in phase III trials for the treatment of non-metastatic clear cell renal cell cancer.

May 23, 2005

Cell Therapeutics issued positive preliminary results of a phase II trial of Xyotax (paclitaxel poliglumex), for the first-line treatment of ovarian cancer. Results from the induction phase of the study indicated that the drug produced an 85% complete response rate, with an additional 12% of subjects experiencing partial response. This 98% response rate was superior to a historical baseline response rate of 80%. This open-label study enrolled 82 patients with treatment naíve stage III/IV ovarian cancer, who received Xyotax in combination with carboplatin on day 1 of a 21 day cycle for 6 cycles.

GTx reported positive results of a phase IIb trial of Acapodene (toremifene citrate), for the prevention of prostate cancer. The drug was previously approved as a treatment for advanced breast cancer. Trial data indicated efficacy in the trial's primary endpoint, producing a 48% reduction in prostate cancer incidence at 12 months in the lowest dosing group, vs. placebo (p=0.45). The higher two dosing groups both produced non- significant reductions in disease incidence. This 4- arm, double blind, placebo-controlled study enrolled 514 patients with high grade prostatic intraepithelial neoplasia (a prostate cancer risk factor) across 64 US sites, who received one of 3 oral doses of Acapodene (20 mg, 40 mg or 60 mg) or placebo once daily for one year.

Regeneron announced preliminary results of a phase I trial of VEGF Trap, for the treatment of advanced cancers. The drug's overall safety profile was positive, with most toxicity issues observed to be mild to moderate, though occasional incidence of serious adverse reactions, including hypertension, was observed. Maximum tolerated dose had not yet been reached. Preliminary evidence of biological activity and efficacy were observed, with VEGF Trap administration producing rapid tumor vascular response and some evidence of efficacy (1 partial response, 2 minor responses and 1 stable disease). This open-label single-agent study had enrolled 27 patients to date, who received one of five dose levels of the drug.

Schering and Novartis reported preliminary results of their phase III "CONFIRM-1" trial of PTZ/ZK (vatalinib), for the treatment of colorectal cancer. Trial data failed to meet their primary endpoint, with the drug producing a non-significant 12% decrease in risk of disease progression (p=0.118), as assessed by central data review. Secondary efficacy was noted, with investigator review producing a 17% reduction in risk of progression (p=0.026); higher efficacy was also noted among subjects with high levels of serum lactate dehydrogenase. Overall tolerability was generally positive, with adverse events generally similar to other VEGF inhibitors. This randomized, double-blind, placebo-controlled study enrolled 1168 subjects, who received an oral dose of either 1250 mg PTK/ZK or placebo once daily, in combination with standard FOLFOX4 chemotherapy. The companies announced that these data, in combination with upcoming data from their CONFIRM-2 phase III trial, would form the basis of regulatory submission in early 2007.

Transgene issued positive results of a phase II trial of their investigational vaccine candidate MVA-MUC1- IL2, for the treatment of non-small cell lung cancer (NSCLC). Trial data yielded preliminary evidence of efficacy, with 37% of subjects experiencing a partial response (PR), 71% of subjects achieving stable disease (PR or stable disease), median time to progression of 6.4 months, median survival of 13 months, and a 53% 1 year survival rate. Furthermore, subjects demonstrating immune response against the MUC1 tumor protein experienced significantly better overall survival (p=0.0035). This open-label study enrolled 44 patients with stage IIIB/IV NSCLC, who received MVA-MUC1-IL2 in combination with cisplatin and vinorelbine chemotherapy.

May 16, 2005

Marshall Edwards has reported preliminary results of a phase IIa trial of phenoxodiol, their chemotherapy sensitizer for the treatment of ovarian cancer. Trial data yielded significant evidence of efficacy, with 11% of subjects experiencing complete response, 22% achieving partial response, and 44% experiencing stable disease. Overall adverse events were positive, with no unanticipated toxicities. This open-label study enrolled 40 patients with ovarian tumors refractory or resistant to treatment with taxane or platinum based chemotherapy. Subjects received phenoxodiol in combination with a standard regimen of either carboplatin (n=20) or paclitaxel (n=20). The company indicated that these positive results warranted continuation of the trial with a third cohort of treatment refractory subjects (n=20), who were to receive standard chemotherapy, with the addition of phenoxodiol only following evidence of progression.

NeoPharm reported combined data from 3 phase I trials of cintredekin besudotox (IL13-PE38QQR), for the treatment of glioblastoma multiforme (GBM). Peritumoral convection enhanced delivery of the drug yielded an overall median survival of 44.0 weeks, compared to 28 weeks for current approved therapies; 6 subjects experienced durable, ongoing disease stabilization of 39+ to 190+ weeks (median 89+ weeks) following a single treatment with the drug. Furthermore, optimal catheter placement was seen to markedly extend median survival (51.7 weeks vs. 39.3 weeks for sub-optimal). These open-label studies enrolled a total of 45 patients with recurrent resectable GBM, who received a single peritumoral infusion of the drug following resection. The company indicated that these results would serve to support the design of their ongoing phase III trial of the drug, dubbed "PRECISE".

May 3, 2004

Roche and Antisoma reported negative results from a phase III trial investigating R1549, a radioactive isotope linked monoclonal antibody for the treatment of ovarian cancer. Results indicated that subjects treated with R1549 did not show superior efficacy compared to subjects in the comparative arm of the trial. The randomized, single-blinded parallel group study, called SMART (Study of Monoclonal Antibody RadioimmunoTherapy) enrolled over 420 subjects with ovarian cancer worldwide. It was designed to compare subjects who received standard care plus R1549 with patients who received standard care alone. Subjects were administered a single dose of R1549 via a catheter into the abdomen after surgery and chemotherapy. The companies announced that the development of R1549 was unlikely to continue.

July 28, 2003

PRIMABioMed Limited reported positive results from a phase Ib trial investigating their Cancer Vac immunotherapy for the treatment of various advanced cancers. Results showed that two subjects who have now continued therapy for 18 months have experienced no progression of their disease. One subject with ovarian cancer showed that their disease marker, which was rising before administration of the immunotherapy, was halted and maintained at a stable level. Tumors in the second subject, with kidney cancer, have also remained stable for over a year. All subjects demonstrated an ability to produce an immune response to the tumor protein. The 12-week study enrolled 12 subjects in Australia. The Cancer Vac therapy involves extracting blood cells, manipulating the immune cells by exposing them to the immunotherapeutic product and then re-injecting these cells to induce a specific immune response.

July 14, 2003

EntreMed reported positive results from a phase I trial investigating Panzem (2-Methoxyestradiol (2ME2)), an endogenous estrogen metabolite for the treatment of ovarian cancer. Results showed the drug produced an objective response in one subject with ovarian cancer. The subject demonstrated a 67% reduction in tumor volume and a 78% reduction in the CA125 marker. A maximum tolerated dose was not reached and minimum side effects were reported. The randomized, dose-escalating study enrolled 17 subjects with advanced solid tumors who had an average of six other therapies. The study was conducted by the National Cancer Institute in Bethesda, Maryland. Results were presented at the American Society of Clinical Oncology Annual Meeting in Chicago.<

ILEX Oncology reported positive results from a phase III trial investigating Campath (alemtuzumab), an approved drug, for the first line therapy in subjects with chronic lymphocytic leukemia. Results demonstrated a trend toward longer progression-free survival in subjects taking Campath. Data showed that six subjects achieved molecular remission, which is linked to progression-free survival. The randomized, dose escalating, controlled study enrolled 23 subject who were in remission following first-line therapy with Fludarabine or Fludarabine plus cyclophosphamide. Results were presented at the 2003 Annual Meeting of the American Society of Clinical Oncology.

June 16, 2003

Dendreon reported additional positive results from a phase III trail investigating Provenge, an investigational therapeutic vaccine for the treatment of metastatic prostate cancer. Results showed that Provenge induced a significant T-cell mediated immune response compared with placebo. Data revealed Provenge treated subjects demonstrated an eight-fold increase in T-cell proliferation compared to placebo treated subjects. The double blind, placebo controlled study enrolled men with androgen independent prostate cancer. Provenge treated men, with a Gleason score of seven or less, developed a median change in T-cell mediated immune response seven-fold greater than those seen men with a Gleason score of eight and higher. No apparent benefit from Provenge therapy was observed among subjects with Gleason scores of eight or higher. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor.

AltaRex reported positive results from a phase III trial investigating OvaRex (oregovamab), a murine monoclonal antibody for the treatment of ovarian cancer. Results showed the time to relapse was 13.3 months with OvaRex compared with 10.3 months with placebo treatment. Subjects with optimal surgical cyto-reduction and no evidence of disease following chemotherapy showed a dramatic clinical benefit as compared to placebo. Subjects with less favorable response to surgery and chemotherapy did not appear to benefit from OvaRex. The randomized, multi-center, placebo-controlled study enrolled 145 subjects following front-line surgery and chemotherapy for stage III/IV ovarian cancer. The side effect profile for OvaRex treatment was similar to placebo.

Genta reported positive preliminary results from a phase II trial investigating Genasense (oblimersen sodium), a BCl-2 protein inhibitor for the treatment of non-Hodgkin’s lymphoma. Results show that across all Genasense treatment groups, 10 of 25 subjects (40%) remained stable without progression during all six treatment cycles. Out of 16 previously treated subjects, one subject (6%) achieved a complete response, and six subjects (38%) achieved stable disease when receiving Genasense alone. During disease progression subjects who were diagnosed and who had not previously received chemotherapy then received a combination of Genasense plus a standard regimen consisting of Rituxan(R), cyclophosphamide, doxorubicin, vincristine, and prednisone. The ongoing study enrolled 37 subjects with mantle cell lymphoma. So far, 25 subjects are evaluable for response; 14 of these patients are still receiving treatment. The study was designed to evaluate the effects of Genasense used without chemotherapy, given every 3-4 weeks.

Spectrum Pharmaceuticals reported positive results from a phase III trial investigating satraplatin, an oral platinum compound for the treatment of prostate cancer. Results demonstrated statistically significant superiority in time to disease progression with satraplatin and a doubling of progression-free survival. The median time to disease progression was 5.2 months for satraplatin versus 2.5 months for the control arm. Data showed a median overall survival time of 15 months for subjects treated in the satraplatin arm versus 12 months for subjects in the control arm. The randomized study 50 subjects with hormone-refractory prostate cancer and evaluated satraplatin plus prednisone versus prednisone alone for use as a first-line chemotherapy treatment. A greater than 50% decline in PSA (prostate-specific antigen) was experienced by 33% (9/27) of subjects in the satraplatin arm versus 9% (2/23) of subjects in the control arm.

SuperGen reported positive results from a phase III trial investigating Orathecin (rubitecan), a topoisomerase I-inhibitor for the treatment of advanced ovarian cancer. Results showed that 7% (13/196) of subjects given Orathecin experienced either a complete or partial tumor response compared with less than 1% (1/211) for subjects receiving an alternative treatment. The median time to disease progression was 57 days for subjects receiving Orathecin, versus 47 days for subjects receiving alternative. The primary study end-point was overall survival, with secondary end-points of tumor response and time to disease progression. Most of subjects in the alternative treatment group received a chemotherapeutic agent such as gemcitabine, 5-FU, mitomycin C, capecitabine, or docetaxel. The randomized, comparative clinical study enrolled 409 subjects with advanced pancreatic cancer.

January 21, 2003

ImmunoGen reported results of a phase I dose-escalation study of HuC242-DM1/SB-408075 (cantuzumab mertansine) in subjects with refractory cancer that expresses the CanAg antigen. Dosing was increased in each new cohort of subjects until dose-limiting toxicity was demonstrated. Based on the results, the recommended dose for cantuzumab mertansine is 235 mg/m2 when administered once every three weeks. In addition, one subject with colon cancer exhibited DM1 localization at the tumor site 24 hours after administration of the drug. Furthermore, this subject had a reduction in lung metastases after two and four courses of cantuzumab mertansine

Introgen reported positive results from a phase II trial investigating Advexin (p53 therapy) for the treatment of non-small cell lung cancer. Results showed that approximately 60% of subjects' primary tumors regressed or disappeared, as assessed by both biopsies and by CT scans three months after treatment. Administration of the drug did not appear to increase the side effect caused by radiation treatment. The study enrolled subjects with non-metastatic non-small cell lung cancer who were ineligible to receive alternative treatments. Advexin was administered via injection into tumors at a range of doses over one month.

Rational Therapeutics reported positive results from two phase II trials investigating gemcitabine with cisplatin as a combination therapy in the treatment of relapsed ovarian cancer. In the first study, results showed that the combination therapy achieved a 70% response rate, with more than 20% of subjects achieving complete remission. Subjects who demonstrated the most tumor response also showed the most sensitivity to the drug in ex-vivo laboratory assays. Out of 27 subjects, there were 26% (7) complete and 44% (12) partial responses. Subjects received cisplatin (30 mg/m2) plus gemcitabine (600-750 mg/m2) intravenously. Seventeen subjects underwent ex vivo analyses for correlation with clinical response. The second study enrolled 36 platinum and paclitaxel resistant subjects. Of the 15 subjects that responded, 11 were partial clinical responses and 4 were complete clinical responses. Gemcitabine (750 mg/m2) was administered intravenously over 30 min followed by cisplatin (30 mg/m2).

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