Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian Primary Peritoneal Carcinoma

October 10, 2014 updated by: Washington University School of Medicine

Phase II Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian and Primary Peritoneal Carcinoma

The purpose of this study is to determine if the combination of bevacizumab and pemetrexed have an effect on recurrent ovarian and primary peritoneal carcinoma by looking at progression and survival at 6 months.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients will be treated with pemetrexed 500 mg/m2 IV and Bevacizumab 15 mg/kg IV every 3 weeks.The patient is treated indefinitely until side effects are deemed severe by the investigator or until progression. Disease progression is measured every 6 weeks using RECIST criteria.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Recurrent epithelial ovarian or primary peritoneal carcinoma. Histologic confirmation of the primary tumor is required. Patients with borderline tumors are not eligible.
  • Patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in one dimension (longest dimension to be recorded). Each lesion must by > 20 mm when measured by conventional imaging techniques, including plain radiography, computed tomography and MRI or > 10 mm when measured by spiral CT.
  • Patients must have at least one "target lesion" to assess response by RECIST criteria. Lesions within a previously irradiated field will be considered "non-target" lesions.
  • Patients must have a GOG performance status of 0 or 1.
  • Patients must have the ability to interrupt non-steroidal anti-inflammatory (NSAID) treatment 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
  • Patients must have the ability to take folic acid, vitamin B12 and dexamethasone as described per protocol.
  • Recovery from effects of recent surgery, radiotherapy or chemotherapy.
  • Patients should be free of active infection requiring antibiotics.
  • Any hormonal therapy directed at the tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy (HRT) is permitted.
  • Any other prior therapy directed at the malignant tumor, including immunologic agents and cytotoxic agents, must be discontinued at least three weeks prior to registration.
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment.
  • Patients must have had one prior regimen containing a taxane compound. Patient may have received first-line treatment either intravenously or intraperitoneally.
  • Patients must NOT have received prior therapy with pemetrexed or bevacizumab.
  • Patients may have received a total of < 2 prior cytotoxic chemotherapy regimens (adjuvant therapy plus one additional regimen). Consolidation or extended therapy as part of first line treatment will be considered as a single regimen.
  • Bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTC) grade 1; Platelets greater than or equal to 100,000/ul.
  • Creatinine clearance must be greater than 45 ml/min.
  • Hepatic function: bilirubin less than or equal to 1.5 x ULN. AST and alkaline phosphatase less than or equal to 2.5 x ULN.
  • Neurologic function: neuropathy (sensory and motor) less than or equal to CTC grade 1.
  • Coagulation: prothrombin time (PT) such that the international normalized ratio (INR) is < 1.5 (INR may be between 2 and 3 if a patient is on stable dose of therapeutic warfarin) and a PTT < 1.2 times control.
  • Patients must have signed informed consent.
  • Patients must meet pre-entry requirements.
  • Patients of childbearing potential must have a negative serum pregnancy test prior to study entry, be practicing an effective form of contraception, and cannot be lactating.
  • Patients may have received prior radiotherapy (to less than 25% of bone marrow), but must start at a Level 1 dose reduction.

Exclusion Criteria:

  • Patients with serious, non-healing wound, ulcer or bone fracture.
  • Patients with clinically significant cardiovascular disease:
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • Unstable angina within 6 months prior to study enrollment.
  • New York Heart Association (NYHA) grade II or greater congestive heart failure.
  • Serious cardiac arrhythmia requiring medication.
  • Grade II or greater peripheral vascular disease. Patients with claudication within 6 months.
  • History of myocardial infarction within 6 months.
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
  • Patients with the presence of ascites or other third space fluid which cannot be controlled by drainage.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study or anticipation of need for major surgical procedure during the course of the study.
  • Patients with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, brain metastases, seizure not controlled with standard medical therapy, history of cerebrovascular accident (CVA, stroke), or transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this study.
  • Minor surgical procedures, other than central venous access placement, such as fine needle aspiration or core biopsy within 7 days prior to day 1 of study.
  • Patients with proteinuria. At baseline patients will undergo a urine protein-creatinine ratio (UPCR) (Appendix IV). Patients with a UPCR > 1.0 at screening should be excluded. Urine dipstick for proteinuria may also be used. Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • Patients whose circumstances do not permit completion of the study or the required follow-up.
  • Patients who are pregnant or nursing.
  • Patients under the age of 18.
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer within the last 5 years or whose previous cancer treatment contraindicates this protocol.
  • Prior therapy with anti-angiogenic agents or pemetrexed.
  • Patients with active infection requiring parenteral antibiotics.
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months.
  • Partial or complete small or large bowel obstruction demonstrated radiographically within 3 months prior to study.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study.
  • Known hypersensitivity to any component of bevacizumab.
  • Inability to comply with study and/or follow-up procedures.
  • Life expectancy of less than 12 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pemetrexed and bevacizumab

Pemetrexed 500 mg/m2 IV on Day 1 of each 21 day cycle

Bevacizumab 15 mg/kg IV on Day 1 of each 21 day cycle
Drug: Pemetrexed
Other Names:
  • Alimta
Drug: Bevacizumab
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 6 months
PFS = Period from study entry until disease progression, death, or date of last contact
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Distribution of Progression-free Survival (PFS)
Time Frame: Median follow-up was 25.7 months (range 3.0-47.2 months)
PFS = Period from study entry until disease progression, death, or date of last contact
Median follow-up was 25.7 months (range 3.0-47.2 months)
Distribution of Overall Survival (OS)
Time Frame: Median follow-up was 25.7 months (range 3.0-47.2 months)
OS = observed length of time from entry into the study to death or date of last contact
Median follow-up was 25.7 months (range 3.0-47.2 months)
Toxicity Associated With Bevacizumab and Pemetrexed
Time Frame: 6 months
Detailed serious adverse events and other adverse events are shown in the adverse event module of the results.
6 months
Frequency of Clinical Response
Time Frame: 6 months
As measured by RECIST criteria
6 months
Gene Expression as Assessed by Illumina cDNA Mediated Annealing, Selection, Extension and Ligation (DASL) Microarray From Paraffin-embedded Tumor Specimens With Response to Pemetrexed and Bevacizumab
Time Frame: 6 months
6 months
Association Between Levels of Thymidylate Synthase, Dihydrofolate Reductase, and Glycinamide Ribonucleotide Formyl Transferase and Ovarian Response to Pemetrexed and Bevacizumab
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Columbia University

Investigators

  • Principal Investigator: David G Mutch, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

March 18, 2009

First Submitted That Met QC Criteria

March 23, 2009

First Posted (Estimate)

March 24, 2009

Study Record Updates

Last Update Posted (Estimate)

October 20, 2014

Last Update Submitted That Met QC Criteria

October 10, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-0508 / 201102272

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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