Bevacizumab Plus Ipilimumab in Patients With Unresectable Stage III or IV Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
Bristol-Myers Squibb
Information provided by (Responsible Party):
F. Stephen Hodi, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00790010
First received: November 12, 2008
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

The purpose of this research study is to determine the safety of using the study drugs bevacizumab and ipilimumab together, and the doses in combination which can be given to people safely. This study also seeks to investigate whether using both study drugs lengthens the amount of time before the participants melanoma worsens.


Condition Intervention Phase
Melanoma
Drug: Bevacizumab Plus Ipilimumab Cohort 1
Drug: Bevacizumab Plus Ipilimumab Cohort 2
Drug: Bevacizumab Plus Ipilimumab Cohort 3
Drug: Bevacizumab Plus Ipilimumab Cohort 4
Phase 1

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: A Phase I Trial of Bevacizumab Plus Ipilimumab in Patients With Unresectable Stage III or IV Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To determine the safety, tolerability and maximum tolerated dosing for the combination of bevacizumab plus ipilimumab in patients with unresectable stage III or stage IV melanoma [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the best overall response rate by standard solid tumor response criteria, disease control rate, time to tumor progression, and duration of response for the combination of bevacizumab plus ipilimumab in this patient population [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To perform correlative studies investigating the effects of this combination therapy on antitumor immunity and tumor vasculature [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: February 2009
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab Plus Ipilimumab Cohort 1
5 subjects for this cohort
Drug: Bevacizumab Plus Ipilimumab Cohort 1
Cohort 1: Ipilimumab 10 mg/kg IV every 3 weeks x 4 doses(induction), then every 3 months (maintenance); Bevacizumab 7.5 mg/kg IV every 3 weeks (continuous)
Other Names:
  • Bevacizumab- also known as Avastin
  • Ipilimumab-also known as MDX-010 or MDX-101 & marketed as Yervoy
Experimental: Bevacizumab Plus Ipilimumab Cohort 2
17 subects for this cohort
Drug: Bevacizumab Plus Ipilimumab Cohort 2
Cohort 2: Ipilimumab 10 mg/kg IV every 3 weeks x 4 doses(induction), then every 3 months (maintenance); Bevacizumab 15 mg/kg IV every 3 weeks (continuous)
Other Names:
  • Bevacizumab- also known as Avastin
  • Ipilimumab-also known as MDX-010 or MDX-101 & marketed as Yervoy
Experimental: Bevacizumab Plus Ipilimumab Cohort 3
12 subjects
Drug: Bevacizumab Plus Ipilimumab Cohort 3
Cohort 3: Ipilimumab 3 mg/kg IV every 3 weeks x 4 doses (induction), then every 3 months (maintenance); Bevacizumab 7.5 mg/kg IV every 3 weeks (continuous)
Other Names:
  • Bevacizumab- also known as Avastin
  • Ipilimumab-also known as MDX-010 or MDX-101 & marketed as Yervoy
Experimental: Bevacizumab Plus Ipilimumab Cohort 4
12 subjects
Drug: Bevacizumab Plus Ipilimumab Cohort 4
Cohort 4: Ipilimumab 3 mg/kg IV every 3 weeks x 4 doses (induction), then every 3 months (maintenance); Bevacizumab 15 mg/kg IV every 3 weeks (continuous)
Other Names:
  • Bevacizumab- also known as Avastin
  • Ipilimumab-also known as MDX-010 or MDX-101 & marketed as Yervoy

Detailed Description:
  • There are two phases to this research study, Induction Phase and Maintenance Phase.
  • Induction Phase: Participants will receive ipilimumab by an infusion into a vein or central line at weeks 1, 4, 7 and 10 for a total of 4 infusions. Bevacizumab is also given as an infusion into a vein or central line at weeks 1, 4, 7 and 10 along with ipilimumab and then every 3 weeks by itself. During all cycles of study therapy, the participant will have a physical exam on the first day and undergo blood tests at every study visit. At weeks 1, 4, 7, 10 and 12 a urine sample will be obtained for analysis.
  • Chest, abdomen and pelvic CT scans will be performed at week 12. If the scans at week 12 show that the participants cancer has remained stable or decreased, they will be asked to have repeat CT scans in three months.
  • Positron Emission Tomography (PET) scans will be done at week 8 and week 16.
  • Maintenance Phase: If the scans performed at week 12 show the cancer has improved or stayed the same, then the participant will continue to receive bevacizumab every three weeks and undergo a CT scan every 3 months. Also, every 3 months the participant may be eligible to receive additional doses of ipilimumab in addition to the bevacizumab.
  Eligibility

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

Inclusion Criteria:

  • Measurable unresectable Stage III or Stage IV melanoma
  • ECOG Performance Status 0 or 1
  • 4 weeks or greater since treatment
  • Must have recovered from any acute toxicity associated with prior therapy
  • Life expectancy of greater than 12 weeks
  • 18 years of age or older
  • Laboratory values as outlined in protocol
  • Negative screening tests for HIV, active Hepatitis B and Hepatitis C
  • Patients who received prior therapy with anthracyclines should have a baseline MUGA or echo with a normal ejection fraction

Exclusion Criteria:

  • CNS metastases
  • Pregnant or nursing women
  • Prior therapy with bevacizumab or ipilimumab
  • Active infection
  • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic autoimmune disease
  • Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
  • Any underlying medical condition which, in the principal investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
  • Any concurrent medical condition requiring the use of systemic steroids
  • Inadequately controlled hypertension
  • Any 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 study enrollment
  • History of stroke of transient ischemic attack within 6 months prior to study enrollment
  • Significant known vascular disease
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure or significant traumatic injury within 28 days prior to study enrollment
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer or bone fracture
  • Proteinuria at screening
  • Known hypersensitivity to any component of bevacizumab
  • History of hemoptysis within 3 months prior to study enrollment
  • Current, ongoing treatment with full-dose warfarin or its equivalent
  • Current or recent (within 10 days of enrollment) use of aspirin (>325mg/day) or chronic use of other NSAIDs
  • Medications that inhibit platelet function
  • Known involvement of melanoma within gastrointestinal tract
  • Ulcerated skin lesions
  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: NCT00790010

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Dana-Farber Cancer Institute
Genentech, Inc.
Bristol-Myers Squibb
Investigators
Principal Investigator: F. Stephen Hodi, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00790010     History of Changes
Other Study ID Numbers: 08-142, CA184-058, AVF 4122s
Study First Received: November 12, 2008
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
bevacizumab
ipilimumab
unresectable stage III melanoma
unresectable stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Antibodies, Monoclonal
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014