Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer(nsclc)
Treatments at13387, crizotinib
Phase phase 1/phase 2
Targets c-MET, ALK, ROS1, Hsp90
Sponsor Astex Pharmaceuticals
Start date October 2012
End date December 2016
Trial size 228 participants
Trial identifier NCT01712217, 2012-001575-37, AT13387-05

Summary

The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Part A is a single-arm, Phase 1, open-label, dose-escalation design in patients with NSCLC who have already been receiving crizotinib 250 mg by mouth (PO) twice daily (BID) for at least 8 weeks and are still tolerating treatment at that dose. Patients will continue treatment with crizotinib + escalating doses of AT13387 IV weekly for 3 weeks in a 4-week cycle. Each cohort will consist of at least 6 patients until the maximum tolerated dose (MTD) is reached. An additional 12 patients will be treated at the MTD level of AT13387 in combination with crizotinib to confirm the safety profile of the combination at that dose level.
at13387
HSP90 inhibitor
crizotinib Xalkori
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
(Active Comparator)
Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the MTD established in Part A. Part B will enroll 128 patients with NSCLC who have been treated with crizotinib for at least 8 weeks and are still tolerating treatment without evidence of disease progression.
at13387
HSP90 inhibitor
crizotinib Xalkori
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
(Active Comparator)
Part C is an open-label, randomized, Phase 2, Simon's 2-stage design of AT13387 administered alone once weekly for 3 weeks (QW×3) or in combination with crizotinib at the MTD established in Part A.
at13387
HSP90 inhibitor
crizotinib Xalkori
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor

Primary Outcomes

Measure
Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.
time frame: 12 months
Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.
time frame: 18 months
Part C: The objective overall response rate for AT13387 alone and the objective response rate (CR+PR) for AT13387 + crizotinib at Stage 1 and Stage 2 of the Simon's 2-stage design.
time frame: 18 months

Secondary Outcomes

Measure
Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib
time frame: 12 months
Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).
time frame: 12 months
Part B: Assess safety of AT13387 in combination with crizotinib; compare PFS and OS between crizotinib and crizotinib + AT13387; and assess overall response rate (CR + PR) in crizotinib patients who crossover to crizotinib + AT13387
time frame: 18 months
Part C: Assess safety of AT13387 alone and in combination with crizotinib who progressed on crizotinib treatment; and compare the PFS and OS of AT13387 administered alone or in combination with crizotinib
time frame: 18 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Men or women 18 years of age or older 2. Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or rearrangements potentially sensitive to crizotinib 3. Measurable disease 4. Must have been receiving or have received crizotinib 5. Have adequate cardiac, bone marrow, liver and kidney function 6. Must be willing and able to provide written informed consent and comply with the protocol and study procedures Exclusion Criteria: 1. Prior anti-cancer treatment with any HSP90 inhibitor 2. Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug 3. Prior malignancy other than adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, low-grade cervical cancer, non-metastatic prostate cancer, or have been disease-free for at least 3 years 4. Abnormal heart function 5. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors 6. Hypersensitivity of AT13387 or other components of the drug product 7. Treatment with an investigational drug within 3 weeks prior to the first dose of study drug 8. Severe systemic diseases or active uncontrolled infections 9. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Additional Information

Official title A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)
Principal investigator Jean-Charles Soria, MD
Description This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A. Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who progressed on crizotinib at any time.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Astex Pharmaceuticals.
Location data was received from the National Cancer Institute and was last updated in August 2016.