Clinical trial NCT00436501: VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Official title: Phase I/II and Pharmacokinetic Study of Docetaxel Plus VEGF Trap (AVE0005, NSC# 724770) in Patients With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-02-19
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose of VEGF Trap (Phase I)
timeFrame: 21 day cycle, up to 3 cycles
measure: Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Up to 6 months
measure: Median Overall Survival (OS) (Phase II)
timeFrame: Time from start of treatment to time of progression, assessed up to 6 years.
measure: Overall Objective Response Rate According to RECIST (Phase II)
timeFrame: Up to 6 months
measure: Median Progression-Free Survival (PFS) (Phase II)
timeFrame: Time from start of treatment to time of progression, assessed up to 6 years.
Secondary outcomes:
measure: Overall Median Duration of Response (Phase II)
timeFrame: Response assessed following treatment (every 3 weeks), up to 6 years. Study duration January 2007 to May 2013.
measure: Number of Participants With Treatment-related Adverse Effects as Assessed by NCI CTCAE v3.0 (Phase II)
timeFrame: Up to 6 years
measure: Number of Participants With PFS (Phase II)
timeFrame: 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Robert Coleman
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.