Interleukin-2 With Sorafenib (BAY 43-9006) for Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma

NCT ID: NCT00418496

Last Updated: 2017-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-08
• Study Completion Date: 2013-10-31

Brief Summary

The primary objective of this study will be to determine the toxicity and Maximum Tolerated Dose (MTD) of the combination of high dose aldesleukin and sorafenib in previously untreated patients with metastatic or unresectable clear cell renal carcinoma (RCC) and metastatic melanoma.

Detailed Description

Rationale: Previous research indicates that high dose aldesleukin produces tumor regression through upregulation of the patients' immune system. Research suggests that sorafenib directly targets tumors by inhibiting angiogenic activity with possibly some cytotoxicity. Angiogenic refers to the formation of new blood vessels that support tumor growth. Cytotoxicity is the measurement of a chemical's ability to damage or kill cancer cells. Researchers have hypothesized that the complementary ways aldesleukin and sorafenib work, and their non-overlapping toxicity profiles, may create a reasonable combination for the treatment of metastatic renal cell carcinoma and metastatic melanoma. The current Phase I study will evaluate toxicity in patients through assessing various dose levels of sorafenib in combination with aldesleukin.

Purpose: The primary objective is to determine the maximum tolerated dose and characterize the toxicity of high dose aldesleukin and sorafenib in patients with unresectable or metastatic clear cell renal carcinoma and metastatic melanoma. Secondary objectives include determining progression free survival in patients, evaluating in a preliminary manner response rates, and assessing other measurements in study participants.

Treatment: Study participants will be given bolus high dose aldesleukin and sorafenib. Aldesleukin will be provided through intravenous infusions on days 1 through 5. Each 5 day treatment is considered a cycle. The second cycle of aldesleukin will start on day 15. Two cycles are considered 1 course. All study participants will be given the same dose level of aldesleukin. No dose reductions will be permitted. Sorafenib will then be administered on day 29. Since this study will assess the maximum tolerated dose of sorafenib, some study participants will receive different amounts of this drug compared to others depending upon when each individual enrolls in the study. Each group of 3 to 6 study participants will receive a higher dose of sorafenib until the maximum tolerated dose is established. Imagining studies will be performed to determine response to treatment during week 12. If the patient has stable or responding disease, a second course will be administered on the same schedule. Patients without disease response will be given one additional course of aldesleukin past maximal response. When it is decided that no further aldesleukin will be provided to patients, sorafenib at the Food and Drug Administration approved dose may be continued until there is a lack of clinical benefit or intolerable side effects develop. Several tests and exams will be given throughout the study to closely monitor patients.

Conditions

Renal Cancer; Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aldekleukin Plus Dose Escalation Sorafenib

Patients will be admitted to a dedicated nursing unit for HD aldesleukin administration. Patients will receive bolus aldesleukin at a dose of 600,000 IU/Kg every eight hours on days 1-5 with a goal of 10-12 doses.

Group Type: EXPERIMENTAL

Aldesleukin

Intervention Type: DRUG

600,000 IU/kg every 8 hours on days 1-5 (week 1) to a maximum of 12 doses. Another cycle of HD aldesleukin will be started on day 15 (week 3).

Sorafenib

Intervention Type: DRUG

To be initiated at a dose of 200 mg orally. Once it is determined that no further HD aldesleukin therapy will be given, sorafenib may be given daily at the FDA approved dose of 400 mg twice daily until there is lack of clinical benefit or intolerable side effects develop.

Interventions

Aldesleukin

600,000 IU/kg every 8 hours on days 1-5 (week 1) to a maximum of 12 doses. Another cycle of HD aldesleukin will be started on day 15 (week 3).

Intervention Type: DRUG

Sorafenib

To be initiated at a dose of 200 mg orally. Once it is determined that no further HD aldesleukin therapy will be given, sorafenib may be given daily at the FDA approved dose of 400 mg twice daily until there is lack of clinical benefit or intolerable side effects develop.

Intervention Type: DRUG

Other Intervention Names

Proleukin; Nexavar

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed evidence of metastatic/ unresectable clear cell renal carcinoma.
• Patients must have metastatic melanoma with no brain metastases.
• Patients must have measurable disease.
• No prior systemic treatment (One prior systemic treatment is allowed for metastatic melanoma patients. Excluded prior therapies include prior high dose aldesleukin, sorafenib and DTIC/TMZ.)
• Age ≥ 18 years or older

Exclusion Criteria

• Patients who are undergoing or have undergone surgery S weeks.
• Patients who are pregnant (because of possible side effects on the fetus) Effective contraception will be discussed with each patient.
• Patients with uveal melanoma.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Paul Monk

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J. Paul Monk, M.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University

Columbus, Ohio, United States

Countries

United States

References

Monk P, Lam E, Mortazavi A, Kendra K, Lesinski GB, Mace TA, Geyer S, Carson WE 3rd, Tahiri S, Bhinder A, Clinton SK, Olencki T. A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. J Immunother. 2014 Apr;37(3):180-6. doi: 10.1097/CJI.0000000000000023.

Reference Type: RESULT

PMID: 24598448 (View on PubMed)

Related Links

http://cancer.osu.edu

Jamesline 1-800-293-5066

Other Identifiers

NCI-2011-03199

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-06006

Identifier Type: -

Identifier Source: org_study_id