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

NCT01712217 | Completed Phase 1

• 2 other identifiers: AT13387-052012-001575-37
• Study Type: interventional
• Target: 220
• Locations: 5 countries
• Sites: 65

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.

Conditions

Non-small Cell Lung Cancer(NSCLC)

Keywords

Non-small cell lung cancer

Outcome Measures

Primary Outcomes (3)

• Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.

  \- Number of patients with adverse events

  12 months

• 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

• 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 Outcomes (4)

• Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib

  12 months

• Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).

  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

  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

  18 months

Study Arms (3)

AT13387 and Crizotinib

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.

Drug: AT13387; Drug: Crizotinib

Crizotinib versus crizotinib + AT13387

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.

Drug: AT13387; Drug: Crizotinib

AT13387 or AT13387 + crizotinib

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.

Drug: AT13387; Drug: Crizotinib

Interventions

AT13387 DRUG

HSP90 inhibitor

AT13387 and Crizotinib; AT13387 or AT13387 + crizotinib; Crizotinib versus crizotinib + AT13387

Crizotinib DRUG

ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor

Also known as: Xalkori

AT13387 and Crizotinib; AT13387 or AT13387 + crizotinib; Crizotinib versus crizotinib + AT13387

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (65)

Mayo Clinic-Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of California, San Diego Medical Center

La Jolla, California, 92093-0698, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Sharp Clinical Oncology Research-Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine-Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Christiana Hospital

Newark, Delaware, 19713, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612-9497, United States

Location

Northwestern University The Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University Melvin and and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic-Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center Eppley Cancer Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27409, United States

Location

Oncology Hematology in Cincinnati

Cincinnati, Ohio, 45242, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

The Pennsylvania State University-Penn State

Hershey, Pennsylvania, 17033-0850, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

The West Clinic

Germantown, Tennessee, 38138, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington Medical Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, 53579, United States

Location

Atlantic Clinical Cancer Research Unit

Halifax, Nova Scotia, B3H 1V7, Canada

Location

McGill University Health Center

Montreal, Quebec, H3A 1A1, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Cancer Care Manitoba

Winnipeg, R3E OV9, Canada

Location

Centre Hospitalier Regional Universitaire Besancon

Besançon, 25030, France

Location

CHU de Caen-Hopital Cote de Nacre

Caen, 14033, France

Location

Hopital Saint Antoine

Créteil, 94010, France

Location

Centre Hospitalier de Grenoble

Grenoble, 38043, France

Location

CHRU de Lille

Lille, 59037, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Hopital Tenon

Paris, 75020, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Toulouse-Hopital Larrey

Toulouse, 31 059, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Chungbuk National University Hospital

Cheongju-si, 362-711, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Gyeonggi-do, 442-723, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun-gun Jeonnam, 519-809, South Korea

Location

National Cancer Center

Korea, 410-769, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 463-707, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, 08028, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone; Crizotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2012
• First Posted: October 23, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: May 16, 2017
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

FR (10); US (38); CA (5); KR (8); ES (4)