Clinical Trial Result Information

Title of Study:
An open-label, randomized, multicenter trial investigating the efficacy and safety of once weekly (reduced administration frequency) NeoRecormon therapy versus thrice weekly NeoRecormon therapy in anemic patients with metastatic solid tumors (breast, lung, colorectal, ovarian, cervical and prostate cancer) receiving chemotherapy (or scheduled to receive chemotherapy) for at least 9 weeks.

Fast Facts:

Protocol number:	BH20198
Sponsor:	F. Hoffmann-La Roche AG
Company division:	Pharmaceutical
Product name:	NeoRecormon
Generic name:	epoetin beta
Phase of development:	III
Therapeutic area, approved indication:	Anemia
Date of report:	8/1/2007

Clinical study summary:
This was an open-label, randomized, multicenter, two arm study to investigate weekly NeoRecormon therapy, compared to thrice weekly NeoRecormon therapy, in anemic patients receiving chemotherapy (or scheduled to receive chemotherapy). The study was prematurely terminated, following regulatory approval of the once-weekly dosing regimen.

Study center(s) :
11 centers in Czech Republic, Estonia, Germany, Hungary and Latvia.

Objectives:
The primary objective of the study was to demonstrate that once-weekly (reduced administration frequency) NeoRecormon therapy is at least as effective as thrice weekly administration of NeoRecormon in anemic patients with solid tumors receiving chemotherapy.

Methodology:
Eligible patients were randomized into one of two treatment arms to begin treatment with NeoRecormon (starting dose 30,000 IU sc) either as a once weekly administration or as a thrice weekly administration (3 x 10,000 IU). Randomization was stratified by country, baseline Hb (Hb≤10g/dL vs. Hb≥10g/dL) and concomitant chemotherapy (cisplatin-based chemotherapy versus other). Blood pressure, iron parameters, hematology parameters, TEEs and safety laboratory parameters were assessed at baseline and at Weeks 3, 4, 6, 9 and a final visit at Week 12. Iron therapy and transfusions were administered as required and concomitant medications and adverse events recorded on a continuous basis throughout the trial up to 15 days after last dose.

Number of patients (planned/analyzed):
280 planned. 45 enrolled

Diagnosis and main criteria for inclusion:
Anemic (Hb ≤11.0g/dL), adult (≥18 years of age) subjects with metastatic disease of histologically or cytologically documented solid tumors (breast cancer, NSCLC, SCLC, colorectal, ovarian, cervical and prostate cancer) receiving chemotherapy (or scheduled to receive chemotherapy) for at least 9 weeks.

Test product, dose and mode of administration or test procedure:
NeoRecormon (epoetin beta) solution for injection in 10,000 IU, 20,000 IU, or 30,000 IU pre-filled syringes.
30,000 IU administered sc, once weekly for a maximum of 12 doses.
10,000 IU administered sc, thrice weekly for a maximum of 36 doses.

Duration of treatment:
12 weeks.

Reference therapy, dose and mode of administration or reference procedure:
N/A.

Criteria for evaluation (efficacy, safety):
Primary: Time- and baseline-adjusted Hb AUC.
Secondary: Iron parameters over time; iron medication and blood transfusions.
Safety: Adverse events, laboratory test parameters (NCI-CTC grading), vital signs.

Statistical methods:
Baseline demographic data, efficacy and safety data were summarized using descriptive statistics. Due to the early termination of the study, no formal statistical testing was done. Hematology and iron parameters over time were analyzed descriptively. In addition, iron medication and blood transfusions were summarized.

Summary (efficacy, safety, other results):
Efficacy: Despite the limited sample size, the treatment groups were well balanced with regard to demographics and baseline disease characteristics. The median baseline hemoglobin level was comparable between the study arms (9.8g/dL thrice weekly versus 10.0 g/dL once weekly). There were no noteworthy differences between the study arms with respect to mean changes from baseline in hemoglobin levels, hematocrit levels and time/baseline adjusted AUC. A comparable proportion of patients in each study arm received blood transfusions during the study, with the majority receiving one transfusion. No clinically relevant differences between the treatment groups with respect to the change from baseline to last value in any of the iron parameters assessed during the study (serum iron, TIBC, transferrin, TSAT) were seen. Overall, a higher percentage of patients in the thrice weekly NeoRecormon treatment group (75%) received iron supplementation during the trial compared with patients in the once weekly NeoRecormon treatment group (67%).

Safety: There were no clinically relevant differences in the types of adverse events between the two treatment groups, with gastrointestinal disorders being the most frequently reported adverse events during the trial (38% in the thrice weekly group and 29% in the once weekly group). Overall, the most commonly reported gastrointestinal event was nausea which was reported by 21% of patients in the thrice weekly group and 5% of patients in the once weekly group. Serious adverse events were reported by 33% of patients receiving thrice weekly NeoRecormon and 29% of patients in the once weekly group, but none was considered related to treatment. One patient experienced an adverse event leading to dose modification; this was deep vein thrombosis, not considered related to NeoRecormon treatment.
One patient in the thrice weekly NeoRecormon treatment group died as a result of a pulmonary hemorrhage and one patient in the once weekly NeoRecormon treatment group died as a result of underlying disease progression. Neither death was considered by the investigator to be related to trial treatment.
No clinically relevant differences between the two treatment groups over time were seen with respect to laboratory parameters or vital signs.

Conclusions:
The results of this prematurely terminated trial support a comparable efficacy and safety profile of a once weekly versus thrice weekly dosing regimen of NeoRecormon in patients with solid tumors receiving chemotherapy within the currently approved label, with an intervention hemoglobin level of <11g/dL and an upper hemoglobin target of 13g/dL. No new or unexpected safety findings were identified which would alter the known safety profile of NeoRecormon in cancer patients with symptomatic anemia receiving chemotherapy.

Click here for the protocol registry listing of this trial.