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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Kidney Cancer

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Trial Information

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


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.

Inclusion 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:

- 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)

- AST and 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 QTc interval to > 450 msec for males or to > 470 msec for
females

- LVEF normal by 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose of Erlotinib Hydrochloride When Used in Combination With Sunitinib.

Outcome Description:

The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.

Outcome Time Frame:

Evaluated at each dose level for the duration of the study.

Safety Issue:

Yes

Principal Investigator

Christopher W. Ryan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

OHSU Knight Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000526204

NCT ID:

NCT00425386

Start Date:

November 2006

Completion Date:

Related Keywords:

  • Kidney Cancer
  • stage III renal cell cancer
  • stage IV renal cell cancer
  • clear cell renal cell carcinoma
  • recurrent renal cell cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
OHSU Knight Cancer InstitutePortland, Oregon  97239
University of Southern CaliforniaLos Angeles, California  90033
Salem HospitalSalem, Oregon  97309