Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma, Ovarian Epithelial

Peritoneal Neoplasms

Fallopian Tube Neoplasms

Carcinoma

Disease Attributes

Genital Neoplasms, Female

Urogenital Neoplasms

Fallopian Tube Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Endocrine System Diseases

Gonadal Disorders

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Aflibercept

Endothelial Growth Factors

Mitogens

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

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.

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

docetaxel

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).

ziv-aflibercept

laboratory biomarker analysis

pharmacological study

Robert Coleman

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

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.

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

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

Escalating dose levels of VEGF Trap were administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose (MTD). The MTD is defined as the highest dose level below which 2 or more patients encounter a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD established on absence of observed DLT(s) in either cycle 0 (single agent) or cycle 1 (combination therapy) of any given dose level.

Frequency of clinical response (partial response or complete response) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance all target lesions; Partial Response (PR): \>/= 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): \>/= 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1+ new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.

Overall survival was defined from the date of study entry until death or date of last contact. Median survival time points calculated in the method of Kaplan-Meier. Standard RECIST criteria followed to evaluate response and progression, and all documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, response assessment consistently done after two additional cycles of therapy.

The percentage of participants in the Phase II arm with an objective response defined as a measurable response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Standard RECIST criteria were followed to evaluate response and progression. All documented responses were required to undergo confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, this response assessment was consistently done after two additional cycles of therapy.

Progression-Free Survival was calculated from study entry until documented disease, death or date of last contact.

Duration of the response from time response is achieved until disease progression is detected. Response assessed following treatment (every 3 weeks) for disease progression. Study duration January 2007 to May 2013, approximately six and half years.

Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v3.0 (Phase II)

Progression-free survival (PFS) defined as number of participants out of total in arm that had no disease progression as measured at 6 months. Standard RECIST criteria used to evaluate response and progression. All documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after initial documentation of response. In the absence of new symptoms, response assessment was consistently done after two additional cycles of therapy.

National Cancer Institute (NCI)

Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.

Phase I VEGF Trap, Docetaxel

Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.

Phase II: VEGF Trap, Docetaxel

Phase II VEGF Trap, Docetaxel

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Adenocarcinoma

Clear cell

Endometrioid

Mixed

Serous

Transitional cell

Unclassified

Histological classification of participant cancer based on pathology report from most recent pre-registration diagnostic biopsy or surgery, confirmed within 14 days after registration for baseline measurements/data.

Participant Cancer Histology

Robert Coleman, MD / Professor

Maximum Tolerated Dose of VEGF Trap (Phase I)

Complete Response

Partial Response

Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST)

Median Overall Survival (OS) (Phase II)

Overall Objective Response Rate According to RECIST (Phase II)

Median Progression-Free Survival (PFS) (Phase II)

Number analyzed represents those Phase II participants with response as documented in Outcome Measure 2.

Overall Median Duration of Response (Phase II)

Number of Participants With Treatment-related Adverse Effects as Assessed by NCI CTCAE v3.0 (Phase II)

Phase I, 2 participants had partial response and 3 were stable disease for a total of 5 responses but only 2 had a Clinical Response (confirmed).

Phase II, 46 participants was evaluable out of 49 enrolled for response/toxicity.

Number of Participants With PFS (Phase II)

Complete Study Participation

Phase 1: VEGF Trap Escalating Dose

Phase 2: MTD VEGF Trap + Docetaxel

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer	NCT00436501	Fallopian Tube ... Malignant Tumor... Recurrent Ovari...	docetaxel ziv-aflibercept laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)
VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer	NCT00436501	Fallopian Tube ... Malignant Tumor... Recurrent Ovari...	docetaxel ziv-aflibercept laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)

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