Sorafenib and Erlotinib in Treating Patients With Metastatic or Unresectable Solid Tumors

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib and erlotinib in treating patients with metastatic or unresectable solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborator: National Cancer Institute (NCI)
• Treatments: Erlotinib Hydrochloride; Niacinamide; Sorafenib

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

• Metastatic or unresectable disease

• Standard curative or palliative measures do not exist OR are no longer effective

• Measurable disease by radiography (for patients treated at the maximum tolerated dose [MTD] only)

• Tumor accessible for serial biopsies (for patients treated at the MTD only)

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR

• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• No bleeding diathesis or coagulopathy

Hepatic

• Bilirubin normal

• AST and ALT ≤ 2.5 times ULN

• PT INR ≤ 1.5 unless on full-dose warfarin

Renal

• Creatinine normal OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg or diastolic BP > 90 mm Hg despite medication)

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

Ophthalmic

• No abnormalities of the cornea, including any of the following:

• Dry eye syndrome

• Sjögren's syndrome

• Congenital abnormalities (e.g., Fuch's dystrophy)

• Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)

• Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Gastrointestinal

• No active peptic ulcer disease that would impair the ability to swallow pills

• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Willing to undergo serial biopsies, positron emission tomography, and CT scanning (for patients treated at the MTD only)

• No ongoing or active infection

• No significant traumatic injury within the past 3 weeks

• No history of allergic reaction to drugs of similar chemical or biological composition to study drugs

• No psychiatric illness or social situation that would preclude study compliance

• No other condition that would impair the ability to swallow pills

• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic hematopoietic colony-stimulating factors

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy (except for low dose, non-myelosuppressive radiotherapy) and recovered

Surgery

• More than 3 weeks since prior major surgery

• No prior surgical procedure affecting absorption

Other

• No prior sorafenib or erlotinib

• No other prior agents targeting Raf, vascular endothelial growth factor (VEGF), VEGF receptor, or epidermal growth factor receptor

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)

• No concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St. John's wort])

• No other concurrent anticancer therapy

• Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin) allowed provided PT INR < 1.1 times upper limit of normal (ULN)

• Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided both of the following criteria are met:

• Patient has an in range INR (between 2-3) while on a stable-dose of oral anti-coagulant OR a stable-dose of low molecular weight heparin

• No active bleeding OR pathological condition that would confer a high risk of bleeding (e.g., tumor involving a major vessel or known varices)