Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Patients With Carcinomas of Mullerian Origin

NCT00652119 | Unknown Phase 1 DMC FDA Drug

• 2 other identifiers: 06-426NCI-2010-00091
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this clinical research study is to learn about the safety and tolerability of paclitaxel and carboplatin when given in combination with Avastin to patients with ovarian, primary peritoneal, or fallopian tube cancer. Objectives: Primary study goals: To investigate the safety and tolerability of carboplatin and paclitaxel administered IP in combination with IV Avastin To determine if Avastin influences the pharmacokinetics of IP administered chemotherapeutic agents Secondary study goals: To determine the systemic exposure to paclitaxel and carboplatin during initial and late cycles of IP dosing. To collect overall survival (OS) and progression-free survival (PFS) To determine changes in IP VEGF levels To determine site of first recurrence Information on CA-125 response and clinical response will be descriptive as secondary goals of this study Exploratory goal: To estimate proportion of patients completing entire course of treatment

Conditions

Ovarian Cancer; Peritoneal Cancer; Fallopian Tube Cancer

Keywords

Ovarian Cancer; Peritoneal Cancer; Fallopian Tube Cancer; Carcinoma of Mullerian Origin; Paclitaxel; Taxol; Carboplatin; Paraplatin®; Avastin; Bevacizumab; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who Complete Entire Treatment Course

  Rate of completers estimated along with a 95% confidence interval to evaluate the tolerability of this regimen.

  Total treatment course = 6 cycles (1 cycle is 21 days)

• Systemic Exposure to Paclitaxel and Carboplatin

  Primary objective of pharmacokinetic studies is to determine whether rate and extent absorption of paclitaxel and carboplatin into systemic circulation when given by the intraperitoneal port (IP) route is influenced by concurrent administration of Avastin by vein. Sampling to define plasma concentration time courses of paclitaxel and carboplatin performed during second cycle without Avastin and fourth cycle of therapy with Avastin. Pharmacokinetic parameters and variables calculated according to standard equations. Concentration-time profiles of carboplatin and its metabolites analyzed by noncompartmental methods and/or nonlinear least squares regression. Mean values of pharmacokinetic parameters statistically compared using the two-tailed t-test.

  Second and fourth 21 day cycle

Secondary Outcomes (6)

• Median Progression Free Survival

  From the start of treatment until the time of death or progression, up to 10 years

• Median Overall Survival

  From the start of treatment until the time of death, up to 20 years

• Change in Intraperitoneal VEGF levels

  Cycle 4-6 day 8, day 1 of cycles 7-12 and 16-18 (cycle is 21 days)

• Site of Cancer First Recurrence

  At the time of first recurrence, assessed up to 10 years

• Change in Plasma CA-125 Level

  1 Year

Study Arms (1)

Paclitaxel + Carboplatin + Avastin

EXPERIMENTAL

Paclitaxel Cycle 1 = 60 mg/m\^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m\^2 IP weekly over 1 hour x 3 weeks of each cycle. Carboplatin Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle. Avastin Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Avastin

Interventions

Paclitaxel DRUG

Cycle 1 = 60 mg/m\^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m\^2 IP weekly over 1 hour x 3 weeks of each cycle.

Also known as: Taxol

Paclitaxel + Carboplatin + Avastin

Carboplatin DRUG

Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle.

Also known as: Paraplatin®

Paclitaxel + Carboplatin + Avastin

Avastin DRUG

Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.

Also known as: Bevacizumab, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Paclitaxel + Carboplatin + Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed epithelial carcinoma of mullerian origin. Specifically, ovarian, primary peritoneal and tubal carcinoma will be allowed. All histologic subtypes are eligible.
• Stage III or IV disease. Stage IV disease by virtue of pleural effusions is allowed but stage IV disease with visceral metastases e.g. lung, liver or abdominal wall is NOT ELIGIBLE. Please discuss any eligibility concerns directly with the P.I., Dr. Richard Penson.
• Patient must have undergone surgical staging and debulking with optimal (less than 1cm) cytoreduction.
• No significant intra-abdominal adhesions or other contraindication to IP port placement.
• Patients must give written informed consent.
• Patient must be age 18 years or older.
• Adequate bone marrow function with an ANC greater that 2,500 and Platelets greater than 100,000 cubic millimeters.
• No proteinuria or less than +1; if greater, 24-hour urine collection must be performed to document less than or equal to 1gm/24 hours of protein.
• ECOG performance status less than or equal to 1.

You may not qualify if:

• Visible disease on post-operative imaging (recognizing the limitations of postoperative CT scans due to postoperative changes there should be unequivocal CT evidence of residual disease greater than 1cm)
• ECOG performance status greater than or equal to 2
• Previous chemotherapy for the disease under study
• Suboptimal (greater than 1 cm residual disease) cytoreduction
• Creatinine greater than 1.5 mg/dL
• SGOT greater than 2 x ULN, bilirubin greater than 1.5 x ULN
• Colostomy or ileostomy
• Concurrent invasive malignancy. (Patients with concurrent superficial endometrial carcinoma are eligible if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium.)
• Known hypersensitivity to E.coli derived products or to any component of Avastin
• Active psychiatric or mental illness that makes informed consent or careful clinical follow-up unlikely
• History of myocardial infarction within 6 months
• History of stroke or transient ischemia attack within 6 months
• Inadequately controlled hypertension greater than 140/90 mm Hg on antihypertensive medication(s)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Clinically significant peripheral vascular disease

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Paclitaxel; Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Richard T Penson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 3, 2008
• Study Start: February 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2021
• Last Updated: August 19, 2020

Record last verified: 2020-08

Locations

US (5)