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
A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion
PRIMARY OBJECTIVE:
I. To compare progression-free survival (PFS) of chemoembolization alone to sorafenib
(sorafenib tosylate) in combination with chemoembolization.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination
with chemoembolization.
II. To evaluate extra-hepatic versus intra-hepatic patterns of failure. III. To determine
the rates of toxicity related to sorafenib in combination with chemoembolization.
TERTIARY OBJECTIVES:
I. To analyze the pharmacogenetic and pharmacokinetic properties of sorafenib including
angiogenesis, monooxygenases, polymorphisms and multidrug resistance (MDR).
II. Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network
(ACRIN) secondary imaging objective: site vs. central evaluation of PFS.
III. To determine the inter-reader concordance for response characterization at four and
eight months by the European Association for the Study of Liver (EASL) criteria.
IV. To determine the value of objective tumor response at four and eight months by the EASL
criteria to predict PFS (by Response Evaluation Criteria in Solid Tumors [RECIST]) and OS.
V. To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of
disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose
of sorafenib tosylate is reached, patients undergo transarterial chemoembolization (TACE)
comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of
10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or
chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats
approximately every 4 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.
ARM II: Patients receive placebo PO BID in the absence of disease progression or
unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached,
patients undergo TACE as in Arm I.
MAINTENANCE THERAPY: After completion of chemoembolization, patients receive sorafenib
tosylate or placebo as in Arm I and II in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up for 4 years.
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