Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian Primary Peritoneal Carcinoma

This study has been completed.
Sponsor:
Collaborator:
Columbia University
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00868192
First received: March 18, 2009
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Carcinoma
Primary Peritoneal Carcinoma
Drug: Pemetrexed
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian and Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    PFS = Period from study entry until disease progression, death, or date of last contact


Secondary Outcome Measures:
  • Distribution of Progression-free Survival (PFS) [ Time Frame: Median follow-up was 25.7 months (range 3.0-47.2 months) ] [ Designated as safety issue: No ]
    PFS = Period from study entry until disease progression, death, or date of last contact

  • Distribution of Overall Survival (OS) [ Time Frame: Median follow-up was 25.7 months (range 3.0-47.2 months) ] [ Designated as safety issue: No ]
    OS = observed length of time from entry into the study to death or date of last contact

  • Toxicity Associated With Bevacizumab and Pemetrexed [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Detailed serious adverse events and other adverse events are shown in the adverse event module of the results.

  • Frequency of Clinical Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    As measured by RECIST criteria

  • 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 ] [ Designated as safety issue: No ]
  • Association Between Levels of Thymidylate Synthase, Dihydrofolate Reductase, and Glycinamide Ribonucleotide Formyl Transferase and Ovarian Response to Pemetrexed and Bevacizumab [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: May 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Alimta
Drug: Bevacizumab
Other Name: Avastin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868192

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Columbia University
Investigators
Principal Investigator: David G Mutch, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00868192     History of Changes
Other Study ID Numbers: 08-0508 / 201102272
Study First Received: March 18, 2009
Results First Received: October 2, 2014
Last Updated: October 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Ovarian Diseases
Urogenital Neoplasms
Bevacizumab
Pemetrexed
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014