Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Massachusetts General Hospital
Brigham and Women's Hospital
Genentech
Information provided by (Responsible Party):
Ursula A. Matulonis, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00856180
First received: February 25, 2009
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to see if it is safe to give Avastin (bevacizumab) and Cyclophosphamide (cytoxan) together without causing serious side effects. Both of these drugs are given in an attempt to block new blood vessel growth to the cancer. The participants cancer will be monitored every six weeks with a Computerized Axial Tomography scan (CT) or Magnetic Resonance Imaging (MRI) scan and/or with a blood test, CA125. The first drug used will be Avastin. If the participants cancer does not grow or shrinks, then they will be kept on this drug alone. If the participants cancer grows and/or their CA125 blood test rises during the Avastin treatment, then we will add Cyclophosphamide.


Condition Intervention
Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Drug: Avastin
Drug: cyclophosphamide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Assess the safety profile of this study regimen with respect to gastrointestinal perforations using a two-stage design. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Assess proportion of patients who remain on study at three months (4 cycles of treatment). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess other toxicity and safety profile of this metronomic antiangiogenic approach. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Assess preliminary response rate and proportion of patients on study at 6 months. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assess progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Assess time to progression and overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: February 2009
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avastin Alone
Intravenous Avastin Alone
Drug: Avastin
Standard dose given intravenously every three weeks
Other Name: bevacizumab
Experimental: Combination Therapy
Avastin plus cyclophosphamide
Drug: Avastin
Standard dose given intravenously every three weeks
Other Name: bevacizumab
Drug: cyclophosphamide
Taken orally once a day
Other Name: cytoxan

Detailed Description:
  • Each treatment cycle lasts three weeks and participants will be seen and examined by their medical team every three weeks.
  • Avastin will be given at the standard dose every three weeks intravenously. After two treatments of Avastin, participants will undergo a repeat CT or MRI scan and a check of their CA125 blood level to determine how the Avastin is affecting their disease. If their cancer is not growing or shrinking and the participant is not having significant side effects, the Avastin will continue for another two cycles.
  • If however, it is discovered that the participant's cancer is growing and they are not experiencing any bad symptoms, then they will start cyclophosphamide orally. Cyclophosphamide is taken at home by mouth every day. The participant's cancer will be rechecked in six weeks, and if the cancer is not growing or is shrinking and the participant is not experiencing any significant side effects, they will continue on the combination therapy.
  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
  • Recurrent cancer and have received and failed a previous platinum-based chemotherapy regimen.
  • Up to 2 prior lines of chemotherapy in the recurrent setting (either platinum-based or non-platinum regimens). Biologic therapies count as a prior line but hormonal therapies do not count.
  • Platinum-resistant or platinum-sensitive recurrence.
  • Must be able to take oral medications and have no evidence of bowel obstruction or partial bowel obstruction
  • Measurable disease by either RECIST or Rustin criteria
  • No chemotherapy, radiation therapy, nor biologic therapy within the last three weeks prior to initiating therapy
  • ECOG score of 0 or 1
  • Life expectancy of 12 weeks or greater
  • 18 years of age or older
  • Laboratory values as outlined in the protocol
  • Patients with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible. Subjects with stage I or II cancer treated with curative intent and no evidence of recurrent disease are also eligible.
  • No evidence of preexisting hypertension. If patient has hypertension, it must be controlled medically (less than 150/90) prior to starting bevacizumab
  • Normal blood coagulation parameters
  • No prior treatment with any other antiangiogenic agents or cyclophosphamide
  • For patients who have received prior doxorubicin or pegylated doxorubicin, LVEF must be 50% or greater.

Exclusion Criteria:

  • Current, recent (within 4 weeks of the first study infusion), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
  • Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
  • Uncontrolled diarrhea
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • NYHA Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to Day 1
  • History of stroke or transient ischemic attack within 6 months prior to day 1
  • Known CNS disease, except for treated brain metastasis
  • Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded.
  • Significant vascular disease within 6 months prior to day 1
  • History of hemoptysis within 1 month prior to day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria as demonstrated by a UPC ratio of 1.0 or greater at screening
  • Known hypersensitivity to any component of bevacizumab
  • Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
  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: NCT00856180

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Brigham and Women's Hospital
Genentech
Investigators
Principal Investigator: Ursula Matulonis, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Ursula A. Matulonis, MD, Medical Oncologist, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00856180     History of Changes
Other Study ID Numbers: 08-148
Study First Received: February 25, 2009
Last Updated: June 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
avastin
bevacizumab
cyclophosphamide
cytoxan
mullerian malignancies

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Bevacizumab
Cyclophosphamide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014