Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
PRIMARY OBJECTIVE: I. To determine investigator assessed progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (non-inferiority) for one versus (vs.) two years of maintenance olaparib. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS360) in the modified intent to treat (ITT) population, with time at risk for progression/death starting 360 days after randomization. II. To evaluate progression-free survival (PFS), PFS2 and overall survival (OS) in the ITT population. III. To evaluate PFS, PFS2, and OS in the as-treated population. IV. To evaluate toxicity, including rates of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and other secondary malignancies, in the safety population. EXPLORATORY OBJECTIVE: I. To evaluate the moderating effect of physician-choice bevacizumab (as stratified) on randomized treatment effect estimates. TRANSLATIONAL OBJECTIVES: I. To assess BRCA reversion mutations in circulating tumor deoxyribonucleic acid (ctDNA) as a predictor of poor response in the BRCA mutated (BRCAm) population. II. To correlate a combined assay assessing quantitative BRCA1 and RAD51C promoter methylation and pathogenic variants in core homologous recombination repair (HRR) genes with clinical homologous recombination deficiency (HRD) testing and outcomes in the BRCA wildtype (BRCAwt) population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (REFERENCE): Patients receive olaparib orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study. ARM II (EXPERIMENTAL): Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.
Phase
3Span
512 weeksSponsor
NRG OncologyClackamas, Oregon
Recruiting
The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer
PRIMARY OBJECTIVES: I. To evaluate and compare overall response rate (ORR) in patients with BRCA1/2 or PALB2 mutant pancreas cancer whose disease has progressed on front-line fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) treated with nab-paclitaxel, gemcitabine, and cisplatin (NABPLAGEM) = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase II) II. To evaluate and compare overall survival (OS) time in patients with BRCA1/2 or PALB2 mutant whose disease has progressed on front-line FOLFIRINOX treated with 1) NABPLAGEM = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase III) SECONDARY OBJECTIVES: I. To evaluate and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria between 2 treatment arms. II. To evaluate and compare duration of response (DoR) between 2 treatment arms. III. To evaluate and compare CA19-9 response (defined as patients with a baseline CA19-9 >= 2x upper limit of normal (ULN) who demonstrate a minimum 25% decrease in CA19-9 at any time point) between 2 treatment arms. IV. To evaluate and compare toxicity profile as assessed by treating clinicians between 2 treatment arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. ARM II: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. After completion of study treatment, patients are followed up within 30 days and then every 3 months for 2 years or until death, whichever comes first.
Phase
2/3Span
278 weeksSponsor
Alliance for Clinical Trials in OncologyClackamas, Oregon
Recruiting
Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer
This study is being done to find out if this approach is better or worse than the usual approach for early rectal cancer. The usual approach is defined as care most people get for early rectal cancer. The usual approach for patients who are not in a study is surgery to remove the rectum or treatment with chemotherapy and radiation therapy, followed by surgery. There are several chemotherapy drugs approved by Health Canada that are commonly used with radiation therapy. For patients who get the usual approach for this cancer, about 90 out of 100 are free of cancer after 5 years. If a patient decides to take part in this study, they will either get a combination of chemotherapy drugs called FOLFOX or CAPOX for up to 12 weeks or will get chemotherapy with radiation therapy for up to 6 weeks. After finishing treatment, and even if treatment is stopped early, the study doctor will watch for side effects and determine which type of surgery would be best. After surgery, patients will be asked to come in every 4 months for 2 years, then every 6 months for an additional year. Then will be checked every year for 2 years. This means seeing the study doctor for up to 5 years after surgery. Patients may be seen more often if your study doctor thinks it is necessary.
Phase
3Span
314 weeksSponsor
Canadian Cancer Trials GroupClackamas, Oregon
Recruiting
A Phase 3 Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria
This is a global, multicenter, randomized, double-blind, parallel group, placebo-controlled phase 3 study investigating the efficacy, safety and tolerability of barzolvolimab in adult participants with Chronic Spontaneous Urticaria (CSU) who are symptomatic despite treatment with non-sedating second generation H1-antihistamines at 1-4 times the locally approved dose. There is a screening period of up to 4 weeks, followed by a 24-week placebo-controlled treatment period, a 28-week active treatment period where all participants receive barzolvolimab followed by a 16-week treatment free period. Approximately 915 adult participants (610 in the active arms and 305 in the placebo arm) will be randomly assigned to the treatment arms.
Phase
3Span
147 weeksSponsor
Celldex TherapeuticsClackamas, Oregon
Recruiting
mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
PRIMARY OBJECTIVE: I. To determine if overall survival (OS) is improved in patients who received mFOLFIRINOX +/- nivolumab in comparison to FOLFOX +/- nivolumab as first-line chemotherapy for metastatic gastroesophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To compare other indices of efficacy, including progression-free survival, objective response rates and duration of response between both treatment arms. II. To evaluate safety and tolerability associated with treatment in each of the treatment arms. III. To evaluate the proportion of patients receiving second line of therapy in both arms. IV. To evaluate tolerability of the treatment in both arms using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). EXPLORATORY OBJECTIVES: I. Exploratory correlative markers will also be measured and evaluated within and between arms to better assess mechanisms and prognostic impact of markers on impact. These will include baseline PD-L1 combined positive score (CPS) and cell free deoxyribonucleic acid (cfDNA) before and after treatment. II. To evaluate and assess the feasibility and compliance associated with not centrally collecting perceived attribution of protocol treatment to reported adverse events. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive fluorouracil intravenously (IV), leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo magnetic resonance imaging (MRI) and a computed tomography (CT) scan throughout the trial. Patients may also undergo blood sample collection on study. ARM II: Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
Phase
3Span
302 weeksSponsor
Alliance for Clinical Trials in OncologyClackamas, Oregon
Recruiting
Carboplatin Chemotherapy Before Surgery for People With High-Risk Prostate Cancer and an Inherited BRCA1 or BRCA2 Gene Mutation
PRIMARY OBJECTIVE: I. To evaluate the pathologic complete response rate at prostatectomy in patients with localized high-risk prostate cancer with germline BRCA2 or BRCA1 mutations who are treated with neoadjuvant carboplatin by central review of source documents. SECONDARY OBJECTIVES: I. To evaluate prostate specific antigen (PSA) progression-free survival post-prostatectomy over the duration of follow-up and specifically, at the 3-year landmark. II. To evaluate metastases free survival and overall survival. III. To evaluate the frequency and severity of toxicities of neoadjuvant carboplatin followed by radical prostatectomy. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients receive carboplatin intravenously (IV) on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis, CT of the chest or chest X-ray, or prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Phase
2Span
226 weeksSponsor
SWOG Cancer Research NetworkClackamas, Oregon
Recruiting
Evaluating the Impact of Social and Genetic Factors on Outcomes in Adolescent and Young Adult Cancer Survivors
PRIMARY OBJECTIVE: I. To establish the association of social-environmental risk factors on both disease-free survival (DFS) and overall survival (OS) for adolescent and young adult cancer survivors. SECONDARY OBJECTIVES: I. To establish the associations of individual resilience factors on DFS and OS for adolescent and young adult cancer survivors. II. To establish the associations of social-environmental risk factors and individual resilience factors on quality of life (QOL) for adolescent and young adult cancer survivors. III. To quantify the extent to which alterations in human gene expression could potentially mediate the effects of social-environmental risk factors and individual resilience factors on DFS, and OS for adolescent and young adult cancer survivors. EXPLORATORY OBJECTIVE: I. To determine whether the relationship between social-environmental risk factors or individual resilience factors and distal outcomes may be moderated by race/ethnicity, sex and gender identity, and geography for adolescent and young adult cancer survivors. OUTLINE: This is an observational study. Participants complete questionnaires about health-related quality of life and undergo collection of blood samples at baseline and 6, 12, 18, and 24 months.
Phase
N/ASpan
329 weeksSponsor
ECOG-ACRIN Cancer Research GroupClackamas, Oregon
Recruiting
Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer
PRIMARY OBJECTIVE: I. To assess whether participants with early stage triple negative breast cancer (TNBC) randomized to receive anthracycline-free, taxane-platinum neoadjuvant chemotherapy with pembrolizumab have non-inferior breast cancer event-free survival (BC-EFS) compared to participants randomized to taxane-platinum-anthracycline neoadjuvant chemotherapy with pembrolizumab. SECONDARY OBJECTIVES: I. To compare pathological complete response (pCR) and residual cancer burden (RCB) rates by randomized arm. II. To compare pCR and RCB rates between randomized arms by tumor infiltrating lymphocytes (TIL) status. III. To compare BC-EFS between randomized arms in the TIL-enriched and non-TIL enriched subgroups. IV. To compare distant relapse-free survival and overall survival by randomized arm. V. To compare invasive breast cancer-free survival after surgery between randomized arms in pCR and residual disease groups. VI. To compare the safety and tolerability by randomized arm among those that initiate therapy. TRANSLATIONAL MEDICINE OBJECTIVE: I. To evaluate concordance and accuracy of an automated stromal TIL (sTIL) algorithm versus (vs.) central pathologist assessed sTILs quantification. PATIENT REPORTED OUTCOME (PRO) OBJECTIVES: I. To compare patient-reported fatigue at 3 weeks after the last neoadjuvant systemic therapy (NAST) dose and, separately, at 18 months after randomization, using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-7a in participants undergoing NAST with taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy. (Quality of Life, Primary) II. To compare physical function experienced by participants undergoing neoadjuvant systemic chemotherapy (NAST) with taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy, within 3-5 weeks post last neoadjuvant systemic therapy dose using the PROMIS-29 Profile physical function subscale score. (Quality of Life, Secondary) III. To compare physical function experienced by participants undergoing NAST taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy at 18 months post registration using the PROMIS-29 Profile physical function subscale score. (Quality of Life, Secondary) IV. To compare other PROMIS-29 Profile subscale scores (sleep disturbance, depression, anxiety, social, pain interference, and pain sensitivity) and GP5 question response by arm within 3-5 weeks post last neoadjuvant systemic therapy dose and at 18 months post registration. (Quality of Life, Exploratory) V. To compare the GP-5 item scores by arm within 3-5 weeks post last neoadjuvant systemic therapy dose and at 18 months post registration. (Quality of Life, Exploratory) VI. To compare select patient-reported outcomes using the Common Terminology Criteria for Adverse Events (PRO-CTCAE) by arm. (Patient-Reported Symptoms of Treatment) BANKING OBJECTIVE: I. To bank physical specimens and digital slides for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive paclitaxel intravenously (IV), carboplatin IV, and pembrolizumab IV on study. Patients then receive doxorubicin IV, cyclophosphamide IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial. ARM II: Patients receive docetaxel IV, carboplatin IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial. Patients are followed up every 6 months for the first 2 years and then annually until 5 years from registration.
Phase
3Span
503 weeksSponsor
SWOG Cancer Research NetworkClackamas, Oregon
Recruiting
Testing Shorter Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With High Risk Prostate Cancer
PRIMARY OBJECTIVE: I. To compare metastasis-free survival, determined using conventional imaging, between men with high-risk prostate cancer randomized to ultrahypofractionation (stereotactic body radiation therapy [SBRT]) to those randomized to moderate hypofractionation and conventional fractionation. SECONDARY OBJECTIVES: I. To compare physician-reported toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 between treatment arms. II. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported urinary function (assessed by Expanded Prostate Cancer Index Composite [EPIC]-26 urinary domains). III. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported bowel function (assessed by EPIC-26 bowel domain). IV. To compare patient-reported fatigue (assessed by Patient Reported Outcomes Measurement Information System [PROMIS]-Fatigue) between treatment arms. V. To compare patient-reported treatment burden (assessed by COmprehensive Score for financial Toxicity [COST]) between treatment arms. VI. To compare failure-free survival between treatment arms. VII. To compare metastasis-free survival based on molecular imaging between treatment arms. VIII. To compare overall survival between treatment arms. EXPLORATORY OBJECTIVES: I. To compare patient-reported sexual function (assessed by EPIC-26 sexual domain) between treatment arms. II. To compare patient-reported quality of life (assessed by European Quality of Life Five Dimension Five Level Scale Questionnaire [EQ-5D-5L]) between treatment arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo SBRT for a total of 5 treatments over 2 weeks. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) on study. ARM II: Patients undergo external beam radiation treatment (EBRT) for 20-45 treatments over 4 to 9 weeks. Patients also undergo CT and/or MRI on study. Patients are followed up every 6 months for 5 years.
Phase
3Span
642 weeksSponsor
NRG OncologyClackamas, Oregon
Recruiting
Cognitive Training for Cancer Related Cognitive Impairment in Breast Cancer Survivors
The goal of this trial is to determine the efficacy of advanced cognitive training for cancer survivors suffering from cancer- and cancer-treatment-related cognitive dysfunction. For millions of cancer survivors, cognitive dysfunction is a prevalent, severe, and persistent problem that has long been associated with poor work-related and health-related outcomes. Evidence suggests that a significant subset of breast cancer survivors (BCS) incur cognitive changes that may persist for years after treatment. Unfortunately, the scientific basis for managing these cognitive changes is extremely limited. Available evidence from pilot studies, including our work, suggests that advanced cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples of BCS, or limited outcome measures. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-blind, randomized controlled trial is to conduct a full-scale efficacy trial to compare advanced cognitive training to attention control in BCS.
Phase
N/ASpan
190 weeksSponsor
NRG OncologyClackamas, Oregon
Recruiting