Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00684996
Other study ID # NCI-2009-01099
Secondary ID NCI-2009-01099CD
Status Terminated
Phase Phase 1/Phase 2
First received May 24, 2008
Last updated April 28, 2014
Start date June 2008
Est. completion date October 2010

Study information

Verified date April 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 5
Est. completion date October 2010
Est. primary completion date October 2010
Accepts healthy volunteers No
Gender Both
Age group N/A and older
Eligibility 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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
etaracizumab
Given IV
Biological:
bevacizumab
Given IV

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States Fremont - Rideout Cancer Center Marysville California
United States SWOG Portland Oregon
United States University of California at Davis Cancer Center Sacramento California

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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) Up to 8 weeks Yes
Primary 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. 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 No
Primary 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. Up to 3 years Yes
Primary 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. From date of registration to date of death due to any cause, assessed up to 3 years No
Primary 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. Up to 3 years No
Secondary Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug 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. 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 Yes
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04987203 - Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Phase 3
Recruiting NCT06391879 - Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Recruiting NCT04623502 - An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy N/A
Completed NCT02853344 - Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427) Phase 2
Terminated NCT04088500 - A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma Phase 2
Completed NCT05070637 - Circulating Tumor Cell Reducing No-touch Nephrectomy N/A
Active, not recruiting NCT03634540 - A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) Phase 2
Not yet recruiting NCT06049030 - A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT01358721 - Phase I Biomarker Study (BMS-936558) Phase 1
Active, not recruiting NCT04503148 - Anesthesia and Cancer Study: Renal Cell Carcinoma N/A
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Not yet recruiting NCT05808608 - A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma Phase 1/Phase 2
Withdrawn NCT03323710 - Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma Phase 2
Not yet recruiting NCT02787915 - DC1s-CTL Cellular Therapy for Renal Cell Carcinoma Phase 1/Phase 2