A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib
- Conditions
- Non-small Cell Lung Cancer(NSCLC)
- Interventions
- Registration Number
- NCT01712217
- Lead Sponsor
- Astex Pharmaceuticals, Inc.
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AT13387 and Crizotinib AT13387 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. Crizotinib versus crizotinib + AT13387 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. AT13387 or AT13387 + crizotinib AT13387 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 and Crizotinib 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. Crizotinib versus crizotinib + AT13387 Crizotinib 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 or AT13387 + crizotinib 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.
- Primary Outcome Measures
Name Time Method Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387. 18 months - Change in tumor measurements by RECIST 1.1 every 8 weeks
Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. 12 months - Number of patients with adverse events
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. 18 months - Change in tumor measurements by RECIST 1.1 every 8 weeks
- Secondary Outcome Measures
Name Time Method 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 18 months * Number of patients with adverse events
* PFS and OS as measured in weeksPart A: Pharmacokinetics of combination treatment with AT13387 and crizotinib 12 months * 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 4Part 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 18 months * Number of patients with adverse events
* PFS and OS as measured in weeks
* Response rate as measured by RECIST 1.1 every 8 weeksPart A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS). 12 months * 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
Trial Locations
- Locations (65)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Northwestern University The Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Sharp Clinical Oncology Research-Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Indiana University Melvin and and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
The West Clinic
🇺🇸Germantown, Tennessee, United States
Mayo Clinic-Scottsdale
🇺🇸Scottsdale, Arizona, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Atlantic Clinical Cancer Research Unit
🇨🇦Halifax, Nova Scotia, Canada
University of Wisconsin-Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
CHU de Caen-Hopital Cote de Nacre
🇫🇷Caen, France
National Cancer Center
🇰🇷Korea, Korea, Republic of
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Mayo Clinic-Rochester
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center Eppley Cancer Center
🇺🇸Omaha, Nebraska, United States
University of California, San Diego Medical Center
🇺🇸La Jolla, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Oncology Hematology in Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
The Pennsylvania State University-Penn State
🇺🇸Hershey, Pennsylvania, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Hopital Saint Antoine
🇫🇷Creteil Cedex, France
Centre Hospitalier Regional Universitaire Besancon
🇫🇷Besancon Cedex, France
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Cancer Care Manitoba
🇨🇦Winnipeg, Canada
Centre Hospitalier de Grenoble
🇫🇷Grenoble, France
McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
🇨🇦Sainte-Foy, Quebec, Canada
CHRU de Lille
🇫🇷Lille cedex, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Hopital Tenon
🇫🇷Paris, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite Cedex, France
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun Jeonnam, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU Toulouse-Hopital Larrey
🇫🇷Toulouse, France
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitari Quiron Dexeus Barcelona
🇪🇸Barcelona, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Yale University School of Medicine-Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States