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

Primary Purpose

Recurrent Renal Cell Cancer, Renal Cell Carcinoma, Stage III Renal Cell Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

etaracizumab

bevacizumab

About this trial

This is an interventional treatment trial for Recurrent Renal Cell Cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Fremont - Rideout Cancer Center
University of California at Davis Cancer Center
University of Michigan
Novant Health Presbyterian Medical Center
SWOG

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Phase II Arm I

Phase II Arm II

Arm Description

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

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.

Outcomes

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)

Progression-free Survival (Phase II)

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)

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)

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)

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

Full Information

NCT ID

NCT00684996

First Posted

May 24, 2008

Last Updated

April 28, 2014

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00684996

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2013

Overall Recruitment Status

Terminated

Study Start Date

June 2008 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Renal Cell Cancer, Renal Cell Carcinoma, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase II Arm I

Arm Type

Active Comparator

Arm Description

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

Arm Title

Phase II Arm II

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

etaracizumab

Other Intervention Name(s)

Abegrin, humanized monoclonal antibody MEDI-522, MEDI-522, monoclonal antibody anti-alpha V beta 3 integrin MEDI-522

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Other Intervention Name(s)

anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

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

Title

Progression-free Survival (Phase II)

Description

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

Title

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)

Description

Time Frame

Up to 3 years

Title

Overall Survival (Phase II)

Description

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.

Time Frame

From date of registration to date of death due to any cause, assessed up to 3 years

Title

Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST), Including Confirmed and Unconfirmed Complete and Partial Responses (Phase II)

Description

Time Frame

Up to 3 years

Secondary Outcome Measure Information:

Title

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Description

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

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher Ryan

Organizational Affiliation

SWOG Cancer Research Network

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fremont - Rideout Cancer Center

City

Marysville

State/Province

California

ZIP/Postal Code

95901

Country

United States

Facility Name

University of California at Davis Cancer Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Novant Health Presbyterian Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

SWOG

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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