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

Non-small Cell Lung Cancer(NSCLC) Clinical Trial

Official title:

A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01712217
• Other study ID #: AT13387-05
• Secondary ID: 2012-001575-37
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 11, 2012
• Last updated: January 17, 2018
• Start date: October 2012
• Est. completion date: May 16, 2017

Study information

• Verified date: January 2018
• Source: Astex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: May 16, 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer(NSCLC)

Intervention

Drug:
• AT13387
HSP90 inhibitor
• Crizotinib
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor

Locations

Country	Name	City	State
Canada	Atlantic Clinical Cancer Research Unit	Halifax	Nova Scotia
Canada	McGill University Health Center	Montreal, Quebec
Canada	Institut Universitaire de Cardiologie et de Pneumologie De Quebec	Sainte-Foy, Quebec
Canada	Princess Margaret Hospital	Toronto, Ontario
Canada	Cancer Care Manitoba	Winnipeg
France	Centre Hospitalier Regional Universitaire Besancon	Besancon Cedex
France	CHU de Caen-Hopital Cote de Nacre	Caen
France	Hopital Saint Antoine	Creteil Cedex
France	Centre Hospitalier de Grenoble	Grenoble
France	CHRU de Lille	Lille cedex
France	Institut Paoli-Calmettes	Marseille
France	Hopital Tenon	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Benite Cedex
France	CHU Toulouse-Hopital Larrey	Toulouse
France	Institut Gustave Roussy	Villejuif
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun Jeonnam
Korea, Republic of	National Cancer Center	Korea
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Universitari Quiron Dexeus Barcelona	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Colorado Denver	Aurora	Colorado
United States	Montefiore Medical Center	Bronx	New York
United States	Northwestern University The Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Oncology Hematology in Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	The West Clinic	Germantown	Tennessee
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	The Pennsylvania State University-Penn State	Hershey	Pennsylvania
United States	Indiana University Melvin and and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of California, San Diego Medical Center	La Jolla	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA Medical Center	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin-Carbone Cancer Center	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University School of Medicine-Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	University of Nebraska Medical Center Eppley Cancer Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Mayo Clinic-Rochester	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sharp Clinical Oncology Research-Sharp Memorial Hospital	San Diego	California
United States	Mayo Clinic-Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.	- Number of patients with adverse events	12 months
Primary	Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.	- Change in tumor measurements by RECIST 1.1 every 8 weeks	18 months
Primary	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.	- Change in tumor measurements by RECIST 1.1 every 8 weeks	18 months
Secondary	Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib	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	12 months
Secondary	Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).	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	12 months
Secondary	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	Number of patients with adverse events; PFS and OS as measured in weeks; Response rate as measured by RECIST 1.1 every 8 weeks	18 months
Secondary	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	Number of patients with adverse events; PFS and OS as measured in weeks	18 months