A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib - Full Text View

Purpose

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.

Condition	Intervention	Phase
Non-small Cell Lung Cancer(NSCLC)	Drug: AT13387 Drug: Crizotinib	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Crizotinib

U.S. FDA Resources

Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:

Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Number of patients with adverse events
Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT133187. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Change in tumor measurements by RECIST 1.1 every 8 weeks
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 ] [ Designated as safety issue: No ]
- Change in tumor measurements by RECIST 1.1 every 8 weeks

Secondary Outcome Measures:

Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Area under the plasma concentration versus time curve (AUC) of AT13387 and crizotinib alone and in combination Week 4
- Maximum concentration (Cmax) OF AT13387 and crizotinib alone and in combination by Week 4
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 ] [ Designated as safety issue: No ]
- Change in tumor measurements by RECIST 1.1 every 8 weeks
- Change in CTCs from baseline every 4 weeks
- Assessment of PFS and OS as measured by weeks
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 ] [ Designated as safety issue: Yes ]
- Number of patients with adverse events
- PFS and OS as measured in weeks
- Response rate as measured by RECIST 1.1 every 8 weeks
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 ] [ Designated as safety issue: Yes ]
- Number of patients with adverse events
- PFS and OS as measured in weeks

Estimated Enrollment:	228
Study Start Date:	October 2012
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AT13387 and Crizotinib 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.	Drug: AT13387 HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor Other Name: Xalkori
Active Comparator: Crizotinib versus crizotinib + AT13387 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.	Drug: AT13387 HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor Other Name: Xalkori
Active Comparator: AT13387 or AT13387 + crizotinib 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.	Drug: AT13387 HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor Other Name: Xalkori

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men or women 18 years of age or older
Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or rearrangements potentially sensitive to crizotinib
Measurable disease
Must have been receiving or have received crizotinib
Have adequate cardiac, bone marrow, liver and kidney function
Must be willing and able to provide written informed consent and comply with the protocol and study procedures

Exclusion Criteria:

Prior anti-cancer treatment with any HSP90 inhibitor
Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug
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
Abnormal heart function
Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
Hypersensitivity of AT13387 or other components of the drug product
Treatment with an investigational drug within 3 weeks prior to the first dose of study drug
Severe systemic diseases or active uncontrolled infections
Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712217

Contacts

Contact: Medpace Recruitment, Center

1-866-872-2349

recruitment@medpace.com

Show 34 Study Locations

Sponsors and Collaborators

Astex Pharmaceuticals

Investigators

Principal Investigator:

Jean-Charles Soria, MD

Institut Gustave Roussy

More Information

No publications provided

Responsible Party:	Astex Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01712217 History of Changes
Other Study ID Numbers:	AT13387-05, 2012-001575-37
Study First Received:	October 11, 2012
Last Updated:	April 24, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Astex Pharmaceuticals:

Non-small cell lung cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms

Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on June 17, 2013