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

NCT00126620 | Completed Phase 1

• 3 other identifiers: PMH-PHL-042CDR0000437855NCI-7178
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and recommended phase II dose

  28 days

Secondary Outcomes (5)

• Pharmacodynamic outcomes

  Pre study and cycle 1

• Pharmacokinetic outcomes

  Pre-study, cycle 1 and cycle 2

• Antitumor activity

  Every 8 wks

• Correlation of EGFR, AKT, ERK and VEGFR with antitumor activity

  If responses or prolonged stable disease are observed

• EGFR activating mutations, gene amplification status, EGFR intron 1 polymorphism if responses or prolonged disease stabilization are seen

  If responses or prolonged stable disease are observed

Study Arms (1)

OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)

EXPERIMENTAL

Sorafenib administered alone for a 1-week run-in period, and then both drugs e given together continuously, with every 28 days considered as a cycle. Three dose levels assessed.

Drug: erlotinib hydrochloride; Drug: sorafenib tosylate

Interventions

erlotinib hydrochloride DRUG

OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)

sorafenib tosylate DRUG

OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)

Eligibility Criteria

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

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)

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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• Quintela-Fandino M, Le Tourneau C, Duran I, Chen EX, Wang L, Tsao M, Bandarchi-Chamkhaleh B, Pham NA, Do T, MacLean M, Nayyar R, Tusche MW, Metser U, Wright JJ, Mak TW, Siu LL. Phase I combination of sorafenib and erlotinib therapy in solid tumors: safety, pharmacokinetic, and pharmacodynamic evaluation from an expansion cohort. Mol Cancer Ther. 2010 Mar;9(3):751-60. doi: 10.1158/1535-7163.MCT-09-0868. Epub 2010 Mar 2.

  PMID: 20197396 RESULT

• Duran I, Hotte SJ, Hirte H, Chen EX, MacLean M, Turner S, Duan L, Pond GR, Lathia C, Walsh S, Wright JJ, Dancey J, Siu LL. Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2007 Aug 15;13(16):4849-57. doi: 10.1158/1078-0432.CCR-07-0382.

  PMID: 17699864 RESULT

MeSH Terms

Interventions

Erlotinib Hydrochloride; Sorafenib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lillian L. Siu, MD, FRCPC

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2005
• First Posted: August 4, 2005
• Study Start: September 1, 2005
• Primary Completion: May 1, 2011
• Last Updated: July 23, 2015

Record last verified: 2015-07

Locations

CA (2)