Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of AMG 386 (trebananib) 15 mg/kg weekly in
combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1). (closed to accrual 10/2/12)
II. To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks
compared to bevacizumab monotherapy in bevacizumab-naïve patients, as measured by 6-month
progression-free survival (PFS6) (Cohort 2).
SECONDARY OBJECTIVES:
I. To further assess the toxicity profile (Cohorts 1 and 2). II. To assess feasibility of
AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1
[closed to accrual 10/2/12]), as measured by the percentage of patients requiring dose
reduction/interruption or discontinuation in the first 2 and subsequent cycles.
III. To determine the radiographic response rate (RR), median progression-free survival
(PFS), and overall survival (OS) in bevacizumab-naïve patients (Cohort 2).
IV. To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10
mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by
overall survival (OS) (cross-over from placebo arm of Cohort 2).
V. To correlate outcome to treatment with tumor genotype, expression profile, and
circulating angiogenesis biomarkers in tumor specimens (Cohort 2).
VI. To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab
therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of
Cohort 2).
VII. To determine the serum pharmacokinetics of AMG 386 in patients receiving bevacizumab
(Cohort 1 and cross-over from placebo arm of Cohort 2).
OUTLINE: This is a safety study (cohort 1 [closed to accrual 10/2/12]) followed by a
randomized study (cohort 2).
Cohort 1: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and
15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity. (closed to accrual
10/2/12)
Cohort 2: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab and trebananib as in Cohort 1.
ARM II: Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days
1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients with disease progression may cross over to Arm I.
After completion of study treatment, patients are followed up at 30 days, every 2 months for
1 year, every 6 months for 1 year, and then annually thereafter.
A Phase III Trial of 6 Versus 12 Treatments of Adjuvant FOLFOX Plus Celecoxib or Placebo for Patients With Resected Stage III Colon Cancer
OBJECTIVES:
Primary
- To compare disease-free survival of patients with resected stage III colon cancer
treated with adjuvant FOLFOX chemotherapy comprising oxaliplatin, fluorouracil, and
leucovorin calcium with versus without celecoxib.
Secondary
- To contribute to an international prospective pooled analysis comparing disease-free
survival of patients treated with these regimens.
- To compare overall survival at 3 years of patients treated with these regimens.
- To contribute to an international prospective pooled analysis comparing disease-free
survival of patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
- To assess toxicities of celecoxib as maintenance adjuvant therapy in these patients.
- To assess differences in cardiovascular-specific events in patients treated with versus
without celecoxib.
- To evaluate differences in toxicities, particularly cumulative peripheral neuropathy,
in patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
OUTLINE: This is a multicenter study. Patients are stratified according to number of
positive lymph nodes* (1-3 vs 4 or more) and concurrent regular low-dose of aspirin (yes vs
no). Patients are randomized to 1 of 4 treatment arms.
NOTE: *Patients with N1c-only disease (i.e., no positive nodes but N1c disease by AJCC 7)
should be stratified to 1-3 nodes.
- Arm I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2
hours, and fluorouracil IV continuously over 46-48 hours (FOLFOX) on day 1. Patients
also receive oral celecoxib once daily on days 1-14 beginning on day 1 of course 2 of
FOLFOX. Courses repeat every 14 days for 12 courses in the absence of disease
progression or unacceptable toxicity.
- Arm II: Patients receive FOLFOX as in arm I and oral placebo once daily on days 1-14
beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the
absence of disease progression or unacceptable toxicity.
- Arm III: Patients receive FOLFOX and celecoxib as in arm I. Courses repeat every 14
days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm IV: Patients receive FOLFOX and placebo as in arm II. Courses repeat every 14 days
for 6 courses in the absence of disease progression or unacceptable toxicity.
In all arms, treatment with celecoxib or placebo continues for 3 years in the absence of
disease progression or unacceptable toxicity.
Blood and tissue samples maybe collected for biomarker analysis and pharmacogenomic studies.
After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for years 2-3, and then annually for 3 years.
Not recruiting | Colon / Rectal Cancer | Multisite
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