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

• ClinicalTrials.gov Identifier: NCT00425386
• Recruitment Status: Completed
• First Posted: January 23, 2007
• Results First Posted: February 16, 2012
• Last Update Posted: May 3, 2017
• Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Christopher Ryan, OHSU Knight Cancer Institute

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Kidney Cancer	Drug: erlotinib hydrochloride; Drug: sunitinib malate; Procedure: biopsy	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
• Study Start Date: August 2006
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: Erlotinib and Sunitinib; 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 Drug: sunitinib malate Will be administered at 50 mg daily, 4 weeks on, 2 weeks off

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; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib. [ Time Frame: 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 ]
   The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.
2. Progression-free Survival at 8 Months [ Time Frame: 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 ]
   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).

Secondary Outcome Measures :

1. To Determine the Safety of Sunitinib in Combination With Erlotinib [ Time Frame: For the duration of the study, up to 7 years ]
2. Median Time to Progression [ Time Frame: For the duration of the study, up to 7 years ]
   The Kaplan-Meier method will be used to estimate the median time to progression.
3. Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease [ Time Frame: From the start of treatment until the criteria for response is met. ]
4. Maximum Percent Change in Tumor Measurement [ Time Frame: Baseline through end of study, up to 7 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

University of Southern California

Los Angeles, California, United States, 90033

United States, Oregon

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States, 97213-2967

OHSU Knight Cancer Institute

Portland, Oregon, United States, 97239-3098

Salem Hospital

Salem, Oregon, United States, 97301

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

• Study Chair: Christopher W. Ryan, MD; OHSU Knight Cancer Institute

More Information

Publications of Results:

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 Francisco, CA. A-361, 2008.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Feng Z, Curti BD, Quinn DI, Strother JM, Chen Z, Agnor R, Beer TM, Ryan CW. A Phase II, Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2022 Oct;20(5):415-422. doi: 10.1016/j.clgc.2022.04.018. Epub 2022 May 5.

• Responsible Party: Christopher Ryan, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00425386
• Other Study ID Numbers: CDR0000526204; P30CA069533 ( U.S. NIH Grant/Contract ); OHSU-2683 ( Other Identifier: Oregon Health & Science University IRB ); OHSU-SOL-06051-LM ( Other Identifier: OHSU Knight Cancer Institute )
• First Posted: January 23, 2007
• Results First Posted: February 16, 2012
• Last Update Posted: May 3, 2017
• Last Verified: May 2017

Keywords provided by Christopher Ryan, OHSU Knight Cancer Institute:

stage III renal cell cancer; stage IV renal cell cancer; clear cell renal cell carcinoma; recurrent renal cell cancer

Additional relevant MeSH terms:

Kidney Neoplasms; Carcinoma, Renal Cell; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Erlotinib Hydrochloride; Sunitinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors