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Oblimersen and Interferon Alfa in Treating Patients With Metastatic Renal Cell Cancer

Primary Purpose

Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
recombinant interferon alfa
oblimersen sodium
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Renal Cell Cancer

Eligibility Criteria

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

Inclusion Criteria: Histologically confirmed, measurable metastatic renal cell cancer; if a nephrectomy was performed in the setting of metastatic disease, post-nephrectomy progression of metastases must be documented Performance status 0-2 (SWOG), life expectancy > 3 months Prior radiation must have been completed > 4 weeks before enrollment, with measurable disease outside of the radiation port WBC > 3500/μl Absolute neutrophil count > 1500/μl Platelets > 100,000/μl Transaminases < 2 x institutional upper limit of normal Serum bilirubin < 1.5 x institutional upper limit of normal (if Gilbert's, up to 2 x upper limit) Serum alkaline phosphatase < 2.5 x institutional upper limit of normal Patients with hepatic metastases may have 50% higher levels of all the above-listed parameters Serum creatinine < 1.5 x institutional upper limit of normal Patients with active or recently-treated autoimmune disease are excluded, as are patients currently receiving or expected to require corticosteroid therapy Prior malignancy is limited to adequately treated non-melanoma skin cancer, cervical carcinoma-in-situ, or any other malignancy for which the patient has been disease-free for at least 5 years Because the effects of G3139 on the unborn fetus or newborn infant are unknown, pregnant or lactating women are excluded, and patients with reproductive potential must agree to use a medically-acceptable form of birth control Patients must have fully recovered from the effects of any prior surgery or medical illness such as infection; those with psychosocial problems that might compromise safety or protocol compliance are excluded Central venous access is required Patients may have received up to two prior biological therapy regimens, excluding exposure to either of the therapy agents and patients may have had no more than one prior chemotherapy regimen; full recovery from all toxicities must have occurred; for high-dose IL-2, at least 8 weeks must have elapsed since prior treatment Written, voluntary informed consent Previous chemotherapy must have been completed at least 3 weeks before treatment under this protocol can be initiated Patients with a history of brain metastases, or who are currently being treated, or have untreated brain metastases, are not eligible; Note: if patient received steroid therapy, at least three weeks must have elapsed prior to entry on this protocol Patients must have normal baseline PT/PTT; Note: For those patients taking low dose coumadin (e.g., as prophylaxis for a venous access device) and INR of up to 1.5 is allowed

Sites / Locations

  • City of Hope

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (recombinant interferon alfa, oblimersen sodium)

Arm Description

Patients receive oblimersen IV continuously on days 1-7 and interferon alfa subcutaneously on days 4, 6, 8, 10, and 12 of course 1 and on days 1, 3, 5, 8, 10, and 12 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive an additional 2 courses past CR.

Outcomes

Primary Outcome Measures

Objective response rate based on the Response Evaluation Criteria In Solid Tumors (RECIST)
Confidence intervals for the response rate will be established by calculating exact 95% confidence limits for a binomial parameter.

Secondary Outcome Measures

Overall survival
Estimated using the product-limit method of Kaplan and Meier.
Progression free survival
Estimated using the product-limit method of Kaplan and Meier.
Time to progression

Full Information

First Posted
May 6, 2003
Last Updated
August 23, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00059813
Brief Title
Oblimersen and Interferon Alfa in Treating Patients With Metastatic Renal Cell Cancer
Official Title
A Phase II Trial of G3139 (Genasense) Anti-Bcl-2 Antisense Oligonucleotide Plus Alpha-Interferon in Metastatic Renal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Phase II trial to study the effectiveness of combining oblimersen with interferon alfa in treating patients who have metastatic renal cell (kidney) cancer. Interferon alfa may interfere with the growth of tumor cells. Oblimersen may increase the effectiveness of interferon alfa by making tumor cells more sensitive to the drug.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the objective response rate of metastatic renal cancer to the combination of G3139 plus α-Interferon (α-IFN). SECONDARY OBJECTIVES: I. To further assess the clinical toxicity of this combination. II. To evaluate the impact of G3139 plus α-IFN on molecular targets involved in the regulation of apoptosis in tumor cells and lymphocytes. III. To evaluate the pharmacokinetics of G3139 when given with α-IFN at this dose and schedule. IV. To evaluate the potential toxicity of this combination on cells of the immune system. OUTLINE: This is a multicenter study. Patients receive oblimersen IV continuously on days 1-7 and interferon alfa subcutaneously on days 4, 6, 8, 10, and 12 of course 1 and on days 1, 3, 5, 8, 10, and 12 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) receive an additional 2 courses past CR. Patients are followed for survival. PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 20-24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (recombinant interferon alfa, oblimersen sodium)
Arm Type
Experimental
Arm Description
Patients receive oblimersen IV continuously on days 1-7 and interferon alfa subcutaneously on days 4, 6, 8, 10, and 12 of course 1 and on days 1, 3, 5, 8, 10, and 12 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive an additional 2 courses past CR.
Intervention Type
Biological
Intervention Name(s)
recombinant interferon alfa
Other Intervention Name(s)
Alferon N, alpha interferon, IFN-A, Intron A, Roferon-A
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Other Intervention Name(s)
augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective response rate based on the Response Evaluation Criteria In Solid Tumors (RECIST)
Description
Confidence intervals for the response rate will be established by calculating exact 95% confidence limits for a binomial parameter.
Time Frame
Start of the treatment until disease progression/recurrence, assessed up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
Time from first day of treatment to time of death due to any cause, assessed up to 5 years
Title
Progression free survival
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 5 years
Title
Time to progression
Time Frame
Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed, measurable metastatic renal cell cancer; if a nephrectomy was performed in the setting of metastatic disease, post-nephrectomy progression of metastases must be documented Performance status 0-2 (SWOG), life expectancy > 3 months Prior radiation must have been completed > 4 weeks before enrollment, with measurable disease outside of the radiation port WBC > 3500/μl Absolute neutrophil count > 1500/μl Platelets > 100,000/μl Transaminases < 2 x institutional upper limit of normal Serum bilirubin < 1.5 x institutional upper limit of normal (if Gilbert's, up to 2 x upper limit) Serum alkaline phosphatase < 2.5 x institutional upper limit of normal Patients with hepatic metastases may have 50% higher levels of all the above-listed parameters Serum creatinine < 1.5 x institutional upper limit of normal Patients with active or recently-treated autoimmune disease are excluded, as are patients currently receiving or expected to require corticosteroid therapy Prior malignancy is limited to adequately treated non-melanoma skin cancer, cervical carcinoma-in-situ, or any other malignancy for which the patient has been disease-free for at least 5 years Because the effects of G3139 on the unborn fetus or newborn infant are unknown, pregnant or lactating women are excluded, and patients with reproductive potential must agree to use a medically-acceptable form of birth control Patients must have fully recovered from the effects of any prior surgery or medical illness such as infection; those with psychosocial problems that might compromise safety or protocol compliance are excluded Central venous access is required Patients may have received up to two prior biological therapy regimens, excluding exposure to either of the therapy agents and patients may have had no more than one prior chemotherapy regimen; full recovery from all toxicities must have occurred; for high-dose IL-2, at least 8 weeks must have elapsed since prior treatment Written, voluntary informed consent Previous chemotherapy must have been completed at least 3 weeks before treatment under this protocol can be initiated Patients with a history of brain metastases, or who are currently being treated, or have untreated brain metastases, are not eligible; Note: if patient received steroid therapy, at least three weeks must have elapsed prior to entry on this protocol Patients must have normal baseline PT/PTT; Note: For those patients taking low dose coumadin (e.g., as prophylaxis for a venous access device) and INR of up to 1.5 is allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim Margolin
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

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Oblimersen and Interferon Alfa in Treating Patients With Metastatic Renal Cell Cancer

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