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

NCT ID: NCT01712217

Last Updated: 2024-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2017-05-16

Brief Summary

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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

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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.

Conditions

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Non-small Cell Lung Cancer(NSCLC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

AT13387

Intervention Type DRUG

HSP90 inhibitor

Crizotinib

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

AT13387

Intervention Type DRUG

HSP90 inhibitor

Crizotinib

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

AT13387

Intervention Type DRUG

HSP90 inhibitor

Crizotinib

Intervention Type DRUG

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

Interventions

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AT13387

HSP90 inhibitor

Intervention Type DRUG

Crizotinib

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

Intervention Type DRUG

Other Intervention Names

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Xalkori

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic-Scottsdale

Scottsdale, Arizona, United States

Site Status

University of California, San Diego Medical Center

La Jolla, California, United States

Site Status

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

Sharp Clinical Oncology Research-Sharp Memorial Hospital

San Diego, California, United States

Site Status

Innovative Clinical Research Institute

Whittier, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Yale University School of Medicine-Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Christiana Hospital

Newark, Delaware, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

Northwestern University The Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University Melvin and and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic-Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center Eppley Cancer Center

Omaha, Nebraska, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

Oncology Hematology in Cincinnati

Cincinnati, Ohio, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

The Pennsylvania State University-Penn State

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

The West Clinic

Germantown, Tennessee, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Atlantic Clinical Cancer Research Unit

Halifax, Nova Scotia, Canada

Site Status

McGill University Health Center

Montreal, Quebec, , Canada

Site Status

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Sainte-Foy, Quebec, , Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, , Canada

Site Status

Cancer Care Manitoba

Winnipeg, , Canada

Site Status

Centre Hospitalier Regional Universitaire Besancon

Besançon, , France

Site Status

CHU de Caen-Hopital Cote de Nacre

Caen, , France

Site Status

Hopital Saint Antoine

Créteil, , France

Site Status

Centre Hospitalier de Grenoble

Grenoble, , France

Site Status

CHRU de Lille

Lille, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

CHU Toulouse-Hopital Larrey

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status

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

Gyeonggi-do, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Hwasun-gun Jeonnam, , South Korea

Site Status

National Cancer Center

Korea, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, , Spain

Site Status

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Countries

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United States Canada France South Korea Spain

Other Identifiers

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2012-001575-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AT13387-05

Identifier Type: -

Identifier Source: org_study_id

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