VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

NCT ID: NCT00436501

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2012-11-30

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.

Conditions

Fallopian Tube Cancer; Malignant Tumor of Peritoneum; Recurrent Ovarian Epithelial Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (VEGF Trap, Docetaxel)

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.

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

25 mg/m\^2 given intravenously (IV) over 1 hour (+/- 10 minutes) following VEGF Trap every 3 weeks starting cycle 1 (21 day cycles)

ziv-aflibercept

Intervention Type: BIOLOGICAL

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).

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Phase II Treatment (VEGF Trap, Docetaxel)

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.

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

25 mg/m\^2 given intravenously (IV) over 1 hour (+/- 10 minutes) following VEGF Trap every 3 weeks starting cycle 1 (21 day cycles)

ziv-aflibercept

Intervention Type: BIOLOGICAL

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).

Interventions

docetaxel

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 Type: DRUG

ziv-aflibercept

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 Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

RP 56976; Taxotere; TXT; aflibercept; vascular endothelial growth factor trap; VEGF Trap; Zaltrap; pharmacological studies

Eligibility Criteria

Inclusion Criteria

Criteria:

• Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer:

Persistent or recurrent disease

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques:

• Must have >= 1 target lesion to assess response;
• Tumors within a previously irradiated field are considered nontarget lesions
• Must have received 1 prior platinum-based chemotherapy regimen (for primary disease) containing carboplatin, cisplatin, or other organoplatinum compound:

Initial treatment may have included any of the following:

• High-dose therapy;
• Consolidation therapy;
• Extended therapy administered after surgical or nonsurgical assessment

• AND Must have received 1 prior platinum-based chemotherapy regimen (for primary disease) containing carboplatin, cisplatin, or other organoplatinum compound:

One additional cytotoxic regimen for recurrent or persistent disease allowed

• No history or evidence of CNS disease, including primary brain tumor or brain metastases
• Zubrod performance status 0-2 (0-1 for patients who received 2 prior regimens [taxane and/or platinum regimens are counted separately])
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• Bilirubin normal
• aspartate aminotransferase / alanine aminotransferase (AST/ALT) < 2.5 times upper limit of normal (ULN)
• Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min
• Prothrombin Time (PT)/international normalized ratio (INR) < 1.5 OR in-range INR 2-3 (if patient is on a stable dose of therapeutic warfarin or low molecular weight heparin)
• PTT < 1.2 times control
• Urine protein:creatinine ratio < 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
• No active infection requiring antibiotics
• No sensory and motor neuropathy >= grade 2
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to VEGF Trap, Magnevist, or fludeoxyglucose F 18
• No history of allergic reaction to paclitaxel or docetaxel or to products mixed in Cremophor EL or Tween 80
• No active bleeding or pathologic condition that would carry a high risk of bleeding, including any of the following:

Known bleeding disorder; Coagulopathy; Peptic ulcer disease; Diverticulitis; Tumor involving major vessels

• No active and/or untreated pulmonary embolism, deep vein thrombosis, or other thromboembolic event (i.e., any condition associated with aberrant clotting or migration of an induced clot)
• No history or evidence of other CNS disease, including any of the following:

Seizures not controlled with standard medical therapy; Cerebrovascular accident; Transient ischemic attack; Subarachnoid hemorrhage within the past 6 months

• No clinically significant cardiovascular disease, including any of the following:

Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg; systolic BP > 180 mm Hg and diastolic BP < 90 mm Hg OR diastolic BP > 90 mm Hg on >= 2 measurements within the past 3 months); Myocardial infarction; Coronary or peripheral artery bypass graft

• No clinically significant cardiovascular disease, including any of the following:

New York Heart association class III or IV congestive heart failure; Serious cardiac arrhythmia requiring medication; Peripheral vascular disease >= grade 2; Unstable angina within the past 6 months; Clinically significant peripheral artery disease (e.g., claudication) within the past 6 months

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• Able to undergo an MRI scan:

No claustrophobia; No implanted devices or metallic foreign bodies not compatible with MRI (e.g., ferromagnetic implants or pacemakers); No known history of allergic reaction to gadolinium contrast agents

• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No significant traumatic injury within the past 28 days
• Recovered from prior therapy to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade =< 1:

Alopecia allowed

• No prior VEGF Trap
• No prior cancer treatment that would preclude study treatment
• Prior paclitaxel allowed
• Prior docetaxel for primary or recurrent disease allowed provided the following criteria are met:

No disease progression during therapy; No disease relapse within 3 months of completing therapy; No persistent disease at the completion of primary therapy

• More than 7 days since prior placement of a vascular access device or core biopsy
• At least 1 week since prior hormonal therapy for the malignant tumor
• At least 4 weeks since other prior therapy, including immunologic agents (6 weeks for nitrosoureas or mitomycin C)
• More than 28 days since prior major surgery, open biopsy, dental extraction, or other dental surgery/procedure resulting in an open wound
• No concurrent major surgery
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy
• No other concurrent investigational agents
• No concurrent hematopoietic growth factors during course 1 of phase I
• Concurrent hormone replacement therapy allowed
• White blood count (WBC) >= 3,000/mm^3

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Coleman

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Countries

United States

References

Coleman RL, Duska LR, Ramirez PT, Heymach JV, Kamat AA, Modesitt SC, Schmeler KM, Iyer RB, Garcia ME, Miller DL, Jackson EF, Ng CS, Kundra V, Jaffe R, Sood AK. Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Lancet Oncol. 2011 Nov;12(12):1109-17. doi: 10.1016/S1470-2045(11)70244-3. Epub 2011 Oct 10.

Reference Type: DERIVED

PMID: 21992853 (View on PubMed)

Related Links

http://www.mdanderson.org

The University of Texas MD Anderson Cancer Center Official Website

Other Identifiers

2006-0329

Identifier Type: -

Identifier Source: secondary_id

P50CA083639

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00218

Identifier Type: -

Identifier Source: org_study_id

NCT00427518

Identifier Type: -

Identifier Source: nct_alias