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

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00790010

Collaborator

Genentech, Inc. (Industry), Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arms

163.1

Anticipated Duration (Months)

15.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 26, 2009

Actual Primary Completion Date :

Jun 22, 2018

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

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 [3 years]

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 [3 years]
To perform correlative studies investigating the effects of this combination therapy on antitumor immunity and tumor vasculature [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02214