Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer

Kidney Cancer Clinical Trial

Official title:

A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425386
• Other study ID #: CDR0000526204
• Secondary ID: P30CA069533OHSU-
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2007
• Last updated: May 1, 2017
• Start date: August 2006
• Est. completion date: March 2014

Study information

• Verified date: May 2017
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Sunitinib and erlotinib may stop the growth of tumor cell by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying the best dose of erlotinib when given together with sunitinib and to see how well they work in treating patients with unresectable or metastatic kidney cancer.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of erlotinib hydrochloride when administered with sunitinib malate in patients with unresectable or metastatic renal cell carcinoma.

• Determine the 8-month progression-free survival of patients treated with this regimen.

Secondary

• Determine the safety of sunitinib malate and erlotinib hydrochloride in these patients.

• Determine the duration of response in these patients.

• Determine the proportion of patients whose best overall response is complete response, partial response, stable disease, or progressive disease.

• Determine the overall survival of patients treated with this regimen.

• Determine the maximum percent reduction in tumor measurement in patients treated with this regimen.

• Collect blood and tissue from these patients for future correlative studies.

OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib hydrochloride.

Patients receive oral sunitinib malate once daily on days 1-28 and oral erlotinib hydrochloride once daily on days 1-42. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of patients experience dose-limiting toxicity. Once the MTD is determined, patients are treated with erlotinib hydrochloride at the MTD and sunitinib malate.

Patients undergo blood and tumor specimen collection periodically during study for future correlative studies.

PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2014
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma with a component of clear cell or papillary carcinoma

• Unresectable or metastatic disease (radiologically or clinically confirmed)

• Measurable disease (= 1 site)

• No known brain metastasis that has not been adequately treated with radiotherapy and/or surgery

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• No grade 3 hemorrhage within the past 4 weeks

• Bilirubin = 1.5 times upper limit of normal (ULN)

• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 2.5 times ULN (< 5 times ULN if due to underlying disease)

• No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)

• Creatinine = 1.5 times ULN

• None of the following cardiovascular conditions within the past 12 months:

• Myocardial infarction

• Severe/unstable angina

• Coronary/peripheral artery bypass graft

• Symptomatic congestive heart failure

• Cerebrovascular accident or transient ischemic attack

• Pulmonary embolism

• Ongoing cardiac dysrhythmia = grade 2

• Atrial fibrillation of any grade

• Prolongation of the corrected QT (QTc) interval to > 450 msec for males or to > 470 msec for females

• Left Ventricular Ejection Fraction (LVEF) normal by Multigated Acquisition (MUGA) or echocardiogram

• No hypertension uncontrolled with medical therapy

• No other active malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ

• No uncontrolled adrenal insufficiency

• No uncontrolled hypothyroidism

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)

• No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs

• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 4 weeks since prior major surgery

• More than 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• More than 4 weeks since prior radiotherapy

• No prior radiotherapy to > 25% of the bone marrow

• More than 28 days since prior investigational agents

• No prior sunitinib malate

• No prior anti-epidermal growth factor receptor therapy (e.g., erlotinib hydrochloride, panitumumab, cetuximab, or gefitinib)

• No concurrent therapeutic warfarin

• Low-dose oral warfarin = 2 mg daily for deep vein thrombosis prophylaxis is allowed after the maximum tolerated dose of erlotinib hydrochloride is determined

• No concurrent Hypericum perforatum (St. John's wort)

• No concurrent chemotherapy or biologic therapy

• No other concurrent anticancer therapy

• No other concurrent investigational agents

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Drug:
• erlotinib hydrochloride
Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily; 100 mg/day, continuous daily; 1.5= 125 mg/day, continuous daily; 150 mg/day, continuous daily
• sunitinib malate
Will be administered at 50 mg daily, 4 weeks on, 2 weeks off

Procedure:
• biopsy
Paraffin block (or unstained slides) of the primary tumor and/or metastatic lesions (as available) and a plasma sample for future correlative studies will be collected. A paraffin block (or at least 10 unstained slides, each of 10 micromillimeter thickness) from the original paraffin-embedded biopsy material taken at the diagnosis will be stored at 4 degrees Celsius.

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California
United States	OHSU Knight Cancer Institute	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Salem Hospital	Salem	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ryan CW, Curti BD, Pattee KJ, et al.: A dose-escalation phase II study of sunitinib (S) plus erlotinib (E) in advanced renal carcinoma (RCC). [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Franc

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib.	The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.	Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years
Primary	Progression-free Survival at 8 Months	Defined as the proportion of patients who are progression free (CR, PR and SD) at 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR)= At least a 30% decrease in the sum of the longest diameter of target lesions, and Stable Disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (20% increase in the sum).	8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney
Secondary	To Determine the Safety of Sunitinib in Combination With Erlotinib		For the duration of the study, up to 7 years
Secondary	Median Time to Progression	The Kaplan-Meier method will be used to estimate the median time to progression.	For the duration of the study, up to 7 years
Secondary	Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease		From the start of treatment until the criteria for response is met.
Secondary	Maximum Percent Change in Tumor Measurement	The maximum percent change in Tumor Measurement is the greatest percent change in longest diameter (LD) for the target lesions from the baseline LD. For patients with no change in LD, the maximum percent change is the lowest increase in LD from the baseline LD.	Baseline through end of study, up to 7 years