Clinical trial NCT00436501
Conditions: Fallopian Tube Cancer Malignant Tumor of Peritoneum Recurrent Ovarian Epithelial Cancer
Keywords: primary peritoneal cavity cancer Ovarian Epithelial Cancer Peritoneal Cancer Fallopian Tube Cancer VEGF Trap aflibercept vascular endothelial growth factor trap Zaltrap docetaxel RP 56976 Taxotere TXT
Sponsor: National Cancer Institute (NCI)
Start date: 2007-01-01; Completion date: 2012-11-01
Enrollment: 58 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial is studying the side effects and best dose of VEGF Trap when given together with docetaxel and to see how well they work in treating patients with persistent or recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving VEGF Trap together with docetaxel may kill more tumor cells

Detailed description:
PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of VEGF Trap and docetaxel in patients with persistent or recurrent ovarian epithelial, primary peritoneal, or fallopian tube cancer. (Phase I \[closed to accrual as of 3/14/2008\]) II. Determine the maximum tolerated dose of VEGF Trap in these patients. (Phase I \[closed to accrual as of 3/14/2008\]) III. Determine the pharmacokinetics of VEGF Trap when administered alone and in combination with docetaxel in these patients. (Phase I \[closed to accrual as of 3/14/2008\]) IV. Determine the effects of VEGF Trap on tumor perfusion and metabolism in these patients. (Phase I \[closed to accrual as of 3/14/2008\]) V. Determine the effect of VEGF Trap and docetaxel on circulating endothelial precursors and circulating endothelial cells in these patients. (Phase I \[closed to accrual as of 3/14/2008\]) VI. Determine the frequency of clinical response (partial response and complete response) in patients treated with this regimen. (Phase II \[open to accrual as of 5/9/2008\]) VII. Determine the progression-free survival (PFS) and overall survival (OS) of patients treated with this regimen. (Phase II \[open to accrual as of 5/9/2008\])

SECONDARY OBJECTIVES:

I. Determine the duration of PFS and OS of patients treated with this regimen. (Phase II) II. Determine the frequency and severity of adverse effects of this regimen in these patients. (Phase II) III. Determine the proportion of patients with PFS at 6 months. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of VEGF Trap followed by a phase II study.

PHASE I (closed to accrual as of 3/14/2008): Patients receive VEGF Trap IV over 1 hour on day 1 of course 1. Patients then receive VEGF Trap IV over 1 hour and docetaxel IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 or 6 patients experience dose-limiting toxicity.

PHASE II (opened to accrual as of 5/9/2008): Patients receive VEGF Trap at the MTD determined in phase I and docetaxel as in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients enrolled in phase I (closed to accrual as of 3/14/2008) undergo blood sample collection periodically for pharmacokinetic studies and surrogate marker studies. These patients also undergo dynamic contrast-enhanced MRI, fludeoxyglucose F 18 positron emission tomography, and CT scan at baseline and on day 1 of courses 1 and 2 to evaluate blood flow parameters and metabolic activity of tumors. Patients enrolled in phase I (closed to accrual as of 3/14/2008) and phase II will also undergo blood collection for Anti-VEGF trap antibody.

After the completion of study treatment, patients are followed at 1 and 2 months and then periodically thereafter.

Arms: arm 1: Phase I (closed to accrual as of 3/14/2008): Patients receive VEGF Trap IV over 1 hour on day 1 of course 1. Patients then receive VEGF Trap IV over 1 hour and docetaxel IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 or 6 patients experience dose-limiting toxicity. arm 2: Phase II (opened to accrual as of 5/9/2008): Patients receive VEGF Trap at the MTD determined in phase I and docetaxel as in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: docetaxel intervention 2: ziv-aflibercept intervention 3: laboratory biomarker analysis intervention 4: pharmacological study
Intervention descriptions: intervention 1: 25 mg/m\^2 given intravenously (IV) over 1 hour (+/- 10 minutes) following VEGF Trap every 3 weeks starting cycle 1 (21 day cycles) intervention 2: Starting dose 2 mg/kg given IV Cycle 0. Phase I Group: Every 3 weeks beginning with Cycle 0 (Completed 03/14/2008); Phase II Group: Every 3 weeks starting cycle 1 (Opened 05/09/2008). intervention 3: Correlative studies intervention 4: Correlative studies

Protocol documents: