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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00059813
First received: May 6, 2003
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: recombinant interferon alfa
Biological: oblimersen sodium
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of G3139 (Genasense) Anti-Bcl-2 Antisense Oligonucleotide Plus Alpha-Interferon in Metastatic Renal Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate based on the Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Start of the treatment until disease progression/recurrence, assessed up to 5 years ] [ Designated as safety issue: No ]
    Confidence intervals for the response rate will be established by calculating exact 95% confidence limits for a binomial parameter.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Time from first day of treatment to time of death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Progression free survival [ 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 ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: August 2003
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (recombinant interferon alfa, oblimersen sodium)
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.
Biological: recombinant interferon alfa
Given SC
Other Names:
  • Alferon N
  • alpha interferon
  • IFN-A
  • Intron A
  • Roferon-A
Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00059813

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Kim Margolin Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00059813     History of Changes
Other Study ID Numbers: NCI-2012-02828, NCI-2012-02828, PHII-42, 5828, N01CM17101
Study First Received: May 6, 2003
Last Updated: August 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferons
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014