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

NCT00425386 | Completed Phase 2 Results DMC

• 4 other identifiers: CDR0000526204P30CA069533OHSU-2683OHSU-SOL-06051-LM
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Kidney Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• To Determine the Safety of Sunitinib in Combination With Erlotinib

  For the duration of the study, up to 7 years

• Median Time to Progression

  For the duration of the study, up to 7 years

• 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.

• Maximum Percent Change in Tumor Measurement

  Baseline through end of study, up to 7 years

Study Arms (1)

Erlotinib and Sunitinib

EXPERIMENTAL

Drug: erlotinib hydrochloride Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily; 1. 100 mg/day, continuous daily; 1.5= 125 mg/day, continuous daily; 2. 150 mg/day, continuous daily Drug: sunitinib malate Will be administered at 50 mg daily, 4 weeks on, 2 weeks off

Drug: erlotinib hydrochloride; Drug: sunitinib malate; Procedure: biopsy

Interventions

erlotinib hydrochloride DRUG

Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily; 1. 100 mg/day, continuous daily; 1.5= 125 mg/day, continuous daily; 2. 150 mg/day, continuous daily

Erlotinib and Sunitinib

sunitinib malate DRUG

Will be administered at 50 mg daily, 4 weeks on, 2 weeks off

Erlotinib and Sunitinib

biopsy PROCEDURE

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.

Erlotinib and Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Southern California

Los Angeles, California, 90033, United States

Location

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, 97213-2967, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

Salem Hospital

Salem, Oregon, 97301, United States

Location

Related Publications (2)

• 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.

  RESULT

• 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.

  PMID: 35688679 DERIVED

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

Erlotinib Hydrochloride; Sunitinib; Biopsy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Indoles; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Christopher Ryan
• Organization: OHSU Knight Cancer Institute

ryanc@ohsu.edu

5034946197

Study Officials

• Christopher W. Ryan, MD

  OHSU Knight Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 19, 2007
• First Posted: January 23, 2007
• Study Start: August 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: March 1, 2014
• Last Updated: May 3, 2017
• Results First Posted: February 16, 2012

Record last verified: 2017-05

Locations

US (4)