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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00652119
Recruitment Status : Active, not recruiting
First Posted : April 3, 2008
Last Update Posted : August 19, 2020
Sponsor:
Collaborators:
Genentech, Inc.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Richard Thomas Penson, Massachusetts General Hospital

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


Condition or disease Intervention/treatment Phase
Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer Drug: Paclitaxel Drug: Carboplatin Drug: Avastin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Trial of Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin
Actual Study Start Date : February 2008
Actual Primary Completion Date : August 2009
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: Paclitaxel + Carboplatin + Avastin

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
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.
Other Name: Taxol

Drug: 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.
Other Name: Paraplatin®

Drug: 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.
Other Names:
  • Bevacizumab
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF




Primary Outcome Measures :
  1. Number of Patients Who Complete Entire Treatment Course [ Time Frame: Total treatment course = 6 cycles (1 cycle is 21 days) ]
    Rate of completers estimated along with a 95% confidence interval to evaluate the tolerability of this regimen.

  2. Systemic Exposure to Paclitaxel and Carboplatin [ Time Frame: Second and fourth 21 day cycle ]
    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.


Secondary Outcome Measures :
  1. Median Progression Free Survival [ Time Frame: From the start of treatment until the time of death or progression, up to 10 years ]
  2. Median Overall Survival [ Time Frame: From the start of treatment until the time of death, up to 20 years ]
  3. Change in Intraperitoneal VEGF levels [ Time Frame: Cycle 4-6 day 8, day 1 of cycles 7-12 and 16-18 (cycle is 21 days) ]
  4. Site of Cancer First Recurrence [ Time Frame: At the time of first recurrence, assessed up to 10 years ]
  5. Change in Plasma CA-125 Level [ Time Frame: 1 Year ]
  6. Clinical Response Rate [ Time Frame: 1 Year ]

    The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed epithelial carcinoma of mullerian origin. Specifically, ovarian, primary peritoneal and tubal carcinoma will be allowed. All histologic subtypes are eligible.
  2. 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.
  3. Patient must have undergone surgical staging and debulking with optimal (less than 1cm) cytoreduction.
  4. No significant intra-abdominal adhesions or other contraindication to IP port placement.
  5. Patients must give written informed consent.
  6. Patient must be age 18 years or older.
  7. Adequate bone marrow function with an ANC greater that 2,500 and Platelets greater than 100,000 cubic millimeters.
  8. 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.
  9. ECOG performance status less than or equal to 1.

Exclusion Criteria:

  1. 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)
  2. ECOG performance status greater than or equal to 2
  3. Previous chemotherapy for the disease under study
  4. Suboptimal (greater than 1 cm residual disease) cytoreduction
  5. Creatinine greater than 1.5 mg/dL
  6. SGOT greater than 2 x ULN, bilirubin greater than 1.5 x ULN
  7. Colostomy or ileostomy
  8. 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.)
  9. Known hypersensitivity to E.coli derived products or to any component of Avastin
  10. Active psychiatric or mental illness that makes informed consent or careful clinical follow-up unlikely
  11. History of myocardial infarction within 6 months
  12. History of stroke or transient ischemia attack within 6 months
  13. Inadequately controlled hypertension greater than 140/90 mm Hg on antihypertensive medication(s)
  14. Any prior history of hypertensive crisis or hypertensive encephalopathy
  15. Clinically significant peripheral vascular disease
  16. Significant vascular disease (e.g. aortic aneurysm, aortic dissection)
  17. Unstable angina
  18. New York Heart Association (NYHA) grade II or greater congestive heart failure
  19. Evidence of coagulopathy or bleeding diathesis
  20. Known central nervous system disease or brain metastases
  21. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 28 (first dose of Avastin), anticipation of need for major surgical procedure during the course of the study
  22. Minor surgical procedures such as fine needle aspirations or core biopsies or laparoscopy for IP catheter placement within 7 days prior to cycle 2 day 8
  23. Open wound, ulcer, or bone fracture
  24. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess; current signs and symptoms of bowel obstruction; current dependency on IV hydration or TPN
  25. Pregnant (positive pregnancy test) or lactating

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00652119


Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Massachusetts General Hospital
Genentech, Inc.
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Richard T Penson, MD Massachusetts General Hospital
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Responsible Party: Richard Thomas Penson, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00652119    
Other Study ID Numbers: 06-426
NCI-2010-00091 ( Registry Identifier: NCI CTRP )
First Posted: April 3, 2008    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Richard Thomas Penson, Massachusetts General Hospital:
Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Carcinoma of Mullerian Origin
Paclitaxel
Taxol
Carboplatin
Paraplatin®
Avastin
Bevacizumab
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Paclitaxel
Bevacizumab
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors