MET/VEGFR2 Inhibitor GSK1363089 and Erlotinib Hydrochloride or Erlotinib Hydrochloride Alone in Locally Advanced or Metastatic NSCLC That Has Not Responded to Previous Chemotherapy

NCT01068587 | Completed Phase 1 DMC

• 3 other identifiers: I196CAN-NCIC-IND196GSK-CAN-NCIC-IND196
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: MET/VEGFR2 inhibitor Foretinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This randomized phase I/II trial is studying the side effects of erlotinib hydrochloride when given together with or without MET/VEGFR2 inhibitor Foretinib and to see how well it works in treating patients with locally advanced or metastatic non-small cell lung cancer that has not responded to previous chemotherapy.

Conditions

Lung Cancer

Keywords

recurrent non-small cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Outcome Measures

Primary Outcomes (4)

• The recommended phase II dose of daily oral MET/VEGFR2 inhibitor Foretinib when given in combination with standard erlotinib hydrochloride therapy (phase I)

  After completion of Phase I portion of the study

  3 years

• Safety, tolerability, dose-limiting toxicities, and pharmacokinetic profile (phase I)

  Assessed from the time of first dose. Results will be analyzed at time of final analysis

  3 years

• Correlation between toxicity and pharmacokinetics (phase I)

  After completion of phase I

  3 years

• Objective tumor response rate (partial or complete response) (phase II)

  After every second cycle

Secondary Outcomes (6)

• Clinical benefit (complete response, partial response, and stable disease for ≥ 8 weeks) (phase II)

  8 weeks

• Tumor size at 8 weeks (phase II)

  8 weeks

• 1-year survival rate (phase II)

  1 year

• Response or stable disease duration (phase II)

  After progression

• Progression-free survival (phase II)

  3 years

Study Arms (2)

Erlotinib

ACTIVE COMPARATOR

Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis

Foretinib plus Erlotinib

ACTIVE COMPARATOR

Drug: MET/VEGFR2 inhibitor Foretinib; Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis

Interventions

MET/VEGFR2 inhibitor Foretinib DRUG

PhaseI and Phase II Arm A: Foretinib PO daily dosing starting cycle 1 day 15 and erlotinib PO daily dosing starting cycle 1 day 1. Recommended Phase II dose to be determine in Phase I.

Foretinib plus Erlotinib

erlotinib hydrochloride DRUG

erlotinib PO daily dosing starting cycle 1 day 1. Recommended Phase II dose to be determine in Phase I.

Erlotinib; Foretinib plus Erlotinib

laboratory biomarker analysis OTHER

Tumour markers alone cannot be used to assess objective tumour response. If markers are initially above the upper normal limit, however, they must normalize for a patient to be considered in complete response

Erlotinib; Foretinib plus Erlotinib

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting all of the following criteria: * Locally advanced or metastatic disease * Failed 1-2 prior chemotherapy regimen * Must be eligible to receive erlotinib therapy (i.e., patients must have received 1-2 prior chemotherapy regimen \[combination unless patient is ≥ 70 years\]) for advanced or metastatic disease * No plan to receive further palliative cytotoxic chemotherapy * EGFR-expression status positive or unknown * Patients who are known to have tumors that are EGFR negative on IHC are not eligible * Presence of clinically and/or radiologically documented measurable disease * At least 1 site of disease must be unidimensionally measurable as follows: * Chest X-ray ≥ 20 mm * CT scan (with slice thickness of ≤ 5 mm) ≥ 10 mm (longest diameter) * Physical exam (using calipers) ≥ 10 mm * Lymph nodes by CT scan ≥ 15 mm (measured in short axis) * Measurable lesions must be outside a previous radiotherapy field unless disease progression has been documented * Must have archival tissue available or undergo a biopsy or FNA prior to registration/ randomization * No appreciable cavitation in central thoracic lesions * Patients with overt bleeding from any site (\> 30 mL bleeding/episode) within 3 months of study entry are not eligible * No untreated brain or meningeal metastases (CT scans are not required to rule this out unless there is a clinical suspicion of CNS disease) * Patients with treated and radiologic or clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids ≥ 1 week prior to entry) PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Patients must have discontinued smoking for ≥ 2 weeks prior to registration, and must be prepared to refrain from cigarette usage until completion of the pharmacokinetic sampling at the end of study course 1 (approximately 6 weeks in total) (Phase I only) * Granulocyte count (AGC) ≥ 1.5 times 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Serum creatinine ≤ 1.5 times upper normal limit (UNL) OR calculated creatinine clearance ≥ 50 mL/min (≥ 0.83 mL/sec) * Bilirubin ≤ 1.5 times UNL * ALT and AST ≤ 2 times UNL * No clinically relevant hemoptysis (\> 5 mL fresh blood) within 4 weeks prior to study entry * Patients with only flecks of blood in sputum are permitted * No other invasive malignancies, unless curatively treated with no evidence of disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 90 days after completion of study therapy * No untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction, including any of the following: * Unstable angina, congestive heart failure, or myocardial infarction within the previous year * Cardiac ventricular arrhythmias requiring medication * History of 2nd or 3rd degree atrioventricular conduction defects * Patients with a significant cardiac history (even if controlled) or prior doxorubicin exposure are required to have a LVEF \> 50% * Patients with proliferative diabetic retinopathy, retinal arteritis, or hemorrhage must undergo full ophthalmological examination prior to entry to this study * Must have resting systolic BP ≤ 150 mm Hg and/or diastolic BP ≤ 100 mm Hg (in the presence or absence of a stable dose of anti-hypertensive medication) * No poorly controlled hypertension * No history of labile hypertension or poor compliance with anti-hypertensive medication * No GI tract disease resulting in an inability to absorb oral medication, including any of the following situations: * Uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis) * Post-surgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency or requires IV hyperalimentation (use of pancreatic enzyme supplementation is allowed) * No active or uncontrolled infections * No serious illnesses or medical conditions that would not permit the patient to be managed according to the protocol * No known hypersensitivity to the study drugs or their components PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than two prior chemotherapy regimens for metastatic NSCLC (excluding adjuvant chemotherapy) * Recovered from any treatment-related toxicities prior to randomization * Persistent cisplatin- or taxane-induced sensory neuropathy ≤ grade 2 is acceptable * No prior therapy with agents acting on the EGFR pathway * No prior therapy with a c-Met inhibitor * At least 21 days since the last dose of chemotherapy * At least 21 days since last fraction of prior radiation therapy * Exceptions may be made for non-myelosuppressive radiation to peripheral areas * More than 14 days since prior major surgery, provided that wound healing has occurred * More than 3 weeks since prior and no other concurrent investigational drugs or anti-cancer therapy * No concurrent CYP3A4 enzyme inducing or inhibiting drugs known to interact with erlotinib hydrochloride, including any of the following: * Enzyme-inducing anticonvulsants * Rifampicin * Rifabutin * St. John wort * Atazanavir * Ketoconazole * Patients with a history of pulmonary embolus or a deep vein thrombosis diagnosed and/or treated within 6 months prior to registration will be excluded.

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

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• GlaxoSmithKline: collaborator

Study Sites (4)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Leighl NB, Tsao MS, Liu G, Tu D, Ho C, Shepherd FA, Murray N, Goffin JR, Nicholas G, Sakashita S, Chen Z, Kim L, Powers J, Seymour L, Goss G, Bradbury PA. A phase I study of foretinib plus erlotinib in patients with previously treated advanced non-small cell lung cancer: Canadian cancer trials group IND.196. Oncotarget. 2017 Jun 28;8(41):69651-69662. doi: 10.18632/oncotarget.18753. eCollection 2017 Sep 19.

  PMID: 29050231 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Natasha Leighl, MD, FRCPC

  Princess Margaret Hospital, Canada

  STUDY CHAIR

• Cheryl Ho, MD

  British Columbia Cancer Agency

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2010
• First Posted: February 15, 2010
• Study Start: January 21, 2010
• Primary Completion: March 21, 2014
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)