A Phase Ib, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumour Activity of Volitinib in Combination With Gefitinib in Patients With Epidermal Growth Factor Receptor-mutated Non-small Cell Lung Cancer Who Have Progressed on Epidermal Growth Factor Receptor Inhibitor Treatment

Hutchison Medipharma Limited1 site in 1 country64 target enrollmentApril 2015

ConditionsNon-Small Cell Lung Cancer

InterventionsVolitinib gefitinib

Overview

Phase: Phase 1
Intervention: Volitinib
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hutchison Medipharma Limited
Enrollment: 64
Locations: 1
Primary Endpoint: Number of adverse events and serious adverse events
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1b, open-label, multicentre study of AZD6094 in combination with gefitinib in patients with epidermal growth factor receptor (EGFR) mutation positive (m+) and progressed on EGFR Tyrosine kinase inhibitor (TKI) treatment.

Detailed Description

A total of 53 patients will be enrolled in the safety run-in and expansion phases: * Safety run-in phase - patients with EGFR mutation-positive (EGFRm+), locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on previous EGFT TKI treatment.In the safety run-in phase of the study, the sample size may vary, depending on the number of dose levels evaluated and the number of Dose Limiting Toxicities (DLTs) observed in each cohort. * Expansion phase - patients who are EGFRm+ and cMet-positive with locally advanced or metastatic NSCLC, who have progressed on previous EGFR-TKI treatment.

Registry

clinicaltrials.gov

Start Date

April 2015

End Date

September 14, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hutchison Medipharma Limited

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of informed consent prior to any study specific procedures. If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study there will be no penalty or loss of benefit to the patient and he or she will not be excluded from other aspects of the study.
•Male or female aged at least 18 years and older.
•Histologically or cytologically confirmed locally advanced or metastatic NSCLC patients who are harbouring an EGFR mutation known to be associated with EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X). Local test for EGFR mutation is acceptable. In the expansion phase, patients must have a positive cMet test by a central laboratory. Safety run-in phase: EGFR mutation positive. A local EGFR test result is acceptable Expansion phase: EGFR mutation positive and cMet-positive. cMet test is performed by a central lab.
•Radiological documentation of disease progression while on a previous continuous treatment with EGFR-TKI eg, gefitinib or erlotinib. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. The patients must have been treated with an EGFR-TKI with objective clinical benefit (CR/PR) or SD for 3 months, and who have subsequently shown radiological progression on treatment. In addition, other lines of therapy may have been given.
•At least 1 lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
•Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
•Women should agree to use adequate contraceptive measures (as defined in section 5.1), should not be breast feeding, and must have a negative pregnancy test prior to start of dosing or if of child-bearing potential or of non-child- bearing potential must have evidence of this by fulfilling 1 of the following criteria at screening:
•Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
•Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
•Women under 50 years of age would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution.

Exclusion Criteria

•Intervention with any of the following:
•Treatment with an EGFR-TKI within approximately 5x half-life (eg, within 8 days for erlotinib, gefitinib or afatanib, within 10 days for dacomitinib) of the first dose of study treatment
•Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
•Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be strong inhibitors of CYP1A2 (Appendix E)
•Prior or current treatment with AZD6094 or another cMet inhibitor (eg, foretinib, crizotinib, cabozantinib, onartuzumab)
•Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
•Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed ≥4 weeks of the first dose of study treatment.
•Major surgical procedure, (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study
•With the exception of alopecia and CTCAE Grade 2, prior chemotherapy-related neuropathy, any unresolved toxicities from prior therapy and/or pre-study biopsies greater than CTCAE Grade 1 at the time of starting study treatment
•Have non-measurable disease at baseline per RECIST v1.

Arms & Interventions

Volitinib (AZD6094) 600mg + gefitinib 250 mg

Cohort 1: Volitinib（AZD6094） 600 mg od + gefitinib 250 mg od

Intervention: Volitinib

Volitinib (AZD6094) 600mg + gefitinib 250 mg

Cohort 1: Volitinib（AZD6094） 600 mg od + gefitinib 250 mg od

Intervention: gefitinib

Volitinib (AZD6094) 800mg + gefitinib 250 mg

Cohort 2: Volitinib（AZD6094） 800 mg od + gefitinib 250 mg od

Intervention: gefitinib

Outcomes

Primary Outcomes

Number of adverse events and serious adverse events

Time Frame: From ICF signed to within 28 days after the last dose

the grade of AE event according to CTC AE 4.0

Secondary Outcomes

Disease control rate（DCR)(12 weeks and 24 weeks)
Progression-free survival (PFS）(from enrolled until progression or death due to any cause, assessed up to 2 year)
The Pharmacokinetics (PK) profiles of AZD6094(Cycle 1 Day1 and Day 15)