Clinical trial NCT00418496: Interleukin-2 With Sorafenib (BAY 43-9006) for Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma
Official title: A Phase I Study of Bolus High Dose Interleukin-2 With Sorafenib (BAY 43-9006) in Patients With Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Cancer
Melanoma
Keywords: Unresectable
Metastatic
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Bayer
name: Novartis
First posted: 2007-01-04
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to 1 year
Secondary outcomes:
measure: Determine the progression free survival.
timeFrame: Up to 12 weeks
measure: Evaluate in a preliminary manner the response rate.
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: J. Paul Monk, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.