Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00684996
First received: May 24, 2008
Last updated: April 28, 2014
Last verified: April 2013
  Purpose

This phase I/randomized phase II trial is studying the side effects and best dose of bevacizumab and to see how well it works when given together with or without MEDI-522 in treating patients with unresectable or metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and MEDI-522, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and MEDI-522 may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without MEDI-522 in treating kidney cancer.


Condition Intervention Phase
Recurrent Renal Cell Cancer
Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: etaracizumab
Biological: bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I and a Randomized Phase II Study of Maximal Angiogenic Blockade in Advanced Renal Carcinoma: Bevacizumab (NSC-704865) With or Without MEDI-522 (NSC-719850)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum Tolerated Dose of Bevacizumab , Based on Incidence of Dose-limiting Toxicity (DLT) Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I) [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]
  • Progression-free Survival (Phase II) [ Time Frame: From date of registration to date of first observation of progressive disease, systemic deterioration, or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI CTCAE Version 3.0 (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

  • Overall Survival (Phase II) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Measure from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

  • Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST), Including Confirmed and Unconfirmed Complete and Partial Responses (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of nonmeasurable disease. No new lesions.


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for the first 8 weeks for dose-limiting toxicities, then assessed for adverse events after every cycle (1 cycle = 28 days) of protocol treatment, up to 3 years ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.


Enrollment: 5
Study Start Date: June 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Phase II Arm I
Patients receive bevacizumab (10mg/kg) IV over 30-90 minutes on days 1 and 15.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Active Comparator: Phase II Arm II
Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.
Drug: etaracizumab
Given IV
Other Names:
  • Abegrin
  • humanized monoclonal antibody MEDI-522
  • MEDI-522
  • monoclonal antibody anti-alpha V beta 3 integrin MEDI-522
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the appropriate dose of bevacizumab when administered with humanized monoclonal antibody MEDI-522 in patients with unresectable or metastatic renal cell carcinoma previously treated with sunitinib malate or sorafenib tosylate. (Phase I) II. To compare the progression-free survival of these patients treated with bevacizumab with versus without humanized monoclonal antibody MEDI-522. (Phase II) III. To evaluate the qualitative and quantitative toxicities of bevacizumab and humanized monoclonal antibody MEDI-522 in these patients. (Phase II) IV. To estimate overall survival and RECIST response rate (i.e., confirmed and unconfirmed, complete and partial responses) in both treatment arms. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of bevacizumab followed by a randomized phase II study.

PHASE I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and humanized monoclonal antibody MEDI-522 IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until the recommended phase II dose (RPTD) of bevacizumab is determined.

PHASE II: Patients are stratified according to the number of prior treatment regimens for renal cell carcinoma (1 vs 2) and whether there is a clear cell component (yes vs no). Patients are randomized to 1 of 2 treatment arms:

ARM I: Patients receive bevacizumab (10 mg/kg) IV over 30-90 minutes on days 1 and 15.

ARM II: Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8 mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 3 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Histologically or cytologically confirmed renal cell carcinoma
  • Metastatic or unresectable disease
  • Must have received prior sunitinib malate or sorafenib tosylate for metastatic or unresectable disease
  • Measurable disease
  • No soft tissue disease that has been irradiated within the past 2 months
  • More than 6 months since prior and no concurrent treated or untreated brain metastases
  • Stable, treated brain metastases allowed provided they remained stable for more than 6 months
  • Patients with clinical evidence of brain metastases must have a negative brain CT or MRI scan for metastatic disease
  • Zubrod performance status 0-1
  • Urine protein:creatinine ratio =< 0.5 OR urine protein < 1,000 mg by 24-hour collection
  • Not be pregnant or nursing
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
  • No serious or non-healing wound, ulcer, or bone fracture
  • No clinically relevant bleeding diathesis or coagulopathy
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury within the past 28 days
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No other prior malignancy, except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  • No New York Heart Association class II-IV congestive heart failure
  • No unstable symptomatic arrhythmia requiring medication
  • Chronic, controlled arrhythmias (e.g., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed
  • None of the following cardiovascular conditions within the past 6 months: Arterial thrombosis, Unstable angina, Myocardial infarction, Cerebrovascular accident
  • Must have controlled blood pressure, defined as systolic blood pressure (BP) =< 160 mm Hg and/or diastolic BP =< 90 mm Hg
  • More than 7 days since prior core biopsy
  • At least 14 days since completion of prior therapy and recovered
  • At least 28 days since prior radiotherapy and recovered
  • No prior radiotherapy to >= 25% of bone marrow
  • No more than two prior systemic regimens for renal cell carcinoma (including adjuvant treatment)
  • No prior bevacizumab or humanized monoclonal antibody MEDI-522
  • No major surgical procedure or open biopsy within the past 28 days
  • No concurrent need for a major surgical procedure
  • Concurrent full-dose anticoagulation with warfarin allowed provided INR is between 2-3
  • Concurrent low molecular weight heparin allowed
  • No clinically significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
  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: NCT00684996

Locations
United States, California
Fremont - Rideout Cancer Center
Marysville, California, United States, 95901
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States, 28204
United States, Oregon
SWOG
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Investigators
Principal Investigator: Christopher Ryan Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00684996     History of Changes
Other Study ID Numbers: NCI-2009-01099, NCI-2009-01099, CDR0000596555, S0717, S0717, U10CA032102
Study First Received: May 24, 2008
Results First Received: November 25, 2013
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014