INC280 and Erlotinib Hydrochloride in Treating Patients With Non-small Cell Lung Cancer

NCT01911507 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: 435021UCDCC#238P30CA093373CINC280XUS02T
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. C-Met inhibitor INCB028060 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of c-Met inhibitor INCB028060 and erlotinib, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4

  The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.

  Up to 28 days after a full course of therapy

Secondary Outcomes (6)

• Toxicities as measured by NCI CTCAE V4

  Up to 30 days

• Overall response rate among patients with measurable disease, measured by RECIST 1.1

  Up to 30 days

• Disease control rate, measured by RECIST 1.1

  Up to 30 days

• Progression-free survival

  Duration of time from start of treatment to time of progression or death, assessed up to 30 days

• Overall survival

  Duration of time from the start of treatment to death from any cause, assessed up to 30 days

Study Arms (1)

Treatment ( INCB028, erlotinib)

EXPERIMENTAL

Patients receive INC280 PO BID and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: INC280; Drug: erlotinib hydrochloride

Interventions

INC280 DRUG

Given PO

Also known as: INCB028060

Treatment ( INCB028, erlotinib)

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Treatment ( INCB028, erlotinib)

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent prior to any screening procedures
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Patient is able to swallow and retain oral medication
• Histologically or cytologically documented diagnosis of NSCLC
• Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
• Tumor tissue for correlative studies is mandatory
• Patients in expansion cohort A will have a biopsy (which is standard of care) at the time of progression that shows evidence of MET positivity and meets the criteria for acquired resistance per the Jackman criteria
• Previously received treatment with a single-agent erlotinib
• A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e. G719X, exon 19 deletion, L858R, L861Q)
• Systemic progression of disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] or World Health Organization \[WHO\]) while on continuous treatment with gefitinib or erlotinib
• Patients must have measurable disease; disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy
• Failed 1-2 prior chemotherapies for advanced disease; prior erlotinib is allowed in the dose finding phase and expansion cohort A (Patients in expansion cohort B must be erlotinib naïve and have v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog \[KRAS\] wild type tumor)
• Patients must be willing to be off therapy for a minimum of two weeks (In expansion cohort A patients on erlotinib do not have to discontinue treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy greater than 3 months

You may not qualify if:

• Patients who have had major surgery within 4 weeks of initiation of study medication, excluding the placement of vascular access
• Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =\< 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
• Severely impaired lung function
• Active (acute or chronic) or uncontrolled infection
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Liver disease (i.e. cirrhosis, chronic active hepatitis, chronic persistent hepatitis)
• Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease
• Note: Patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed \> 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
• Receiving drugs known to be strong inducers of cytochrome P450 3A4 (CYP3A4) or inhibiting drugs known to interact with erlotinib including, but not limited to: enzyme-inducing anticonvulsants, rifampicin, rifabutin, St John wort and ketoconazole
• Treatment with proton pump inhibitors within 3 days prior to study entry
• Currently receiving any prohibited medications including vitamins and herbal supplements
• Any other condition that would, in the investigator's judgment, contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 5 mIU/mL)
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after stopping study drug; highly effective contraception methods include:

Sponsors & Collaborators

• University of California, Davis: lead
• Novartis Pharmaceuticals: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of California, Davis

Sacramento, California, 95817, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Karen Kelly

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: July 23, 2013
• First Posted: July 30, 2013
• Study Start: August 27, 2013
• Primary Completion: August 26, 2020
• Study Completion: August 26, 2020
• Last Updated: October 13, 2021

Record last verified: 2021-09

Locations

US (2)