Clinical trial NCT01712217: A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib
Official title: A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer(NSCLC)
Keywords: Non-small cell lung cancer
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.
timeFrame: 12 months
measure: Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
Secondary outcomes:
measure: Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib
timeFrame: 12 months
measure: Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).
timeFrame: 12 months
measure: 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
timeFrame: 18 months
measure: 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
timeFrame: 18 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic-Scottsdale
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research-Sharp Memorial Hospital
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine-Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University The Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and and Bren Simon Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic-Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center Eppley Cancer Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology in Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Hershey
country: United States
facility: The Pennsylvania State University-Penn State
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Carbone Cancer Center
state: Wisconsin
city: Halifax
country: Canada
facility: Atlantic Clinical Cancer Research Unit
state: Nova Scotia
city: Montreal, Quebec
country: Canada
facility: McGill University Health Center
city: Sainte-Foy, Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie De Quebec
city: Toronto, Ontario
country: Canada
facility: Princess Margaret Hospital
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
city: Besancon Cedex
country: France
facility: Centre Hospitalier Regional Universitaire Besancon
city: Caen
country: France
facility: CHU de Caen-Hopital Cote de Nacre
city: Creteil Cedex
country: France
facility: Hopital Saint Antoine
city: Grenoble
country: France
facility: Centre Hospitalier de Grenoble
city: Lille cedex
country: France
facility: CHRU de Lille
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hopital Tenon
city: Pierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Toulouse
country: France
facility: CHU Toulouse-Hopital Larrey
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Hwasun-gun Jeonnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Korea
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus Barcelona
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
Study officials:
References: