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

Primary Purpose

Non-small Cell Lung Cancer(NSCLC)

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AT13387
Crizotinib
Sponsored by
Astex Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer(NSCLC) focused on measuring Non-small cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic-Scottsdale
  • University of California, San Diego Medical Center
  • USC Norris Comprehensive Cancer Center
  • UCLA Medical Center
  • Sharp Clinical Oncology Research-Sharp Memorial Hospital
  • Innovative Clinical Research Institute
  • University of Colorado Denver
  • Yale University School of Medicine-Yale Cancer Center
  • Christiana Hospital
  • Florida Hospital Cancer Institute
  • H. Lee Moffitt Cancer Center & Research Institute
  • Northwestern University The Feinberg School of Medicine
  • University of Chicago
  • Indiana University Melvin and and Bren Simon Cancer Center
  • University of Michigan Medical Center
  • Barbara Ann Karmanos Cancer Institute
  • Mayo Clinic-Rochester
  • Washington University School of Medicine
  • University of Nebraska Medical Center Eppley Cancer Center
  • Dartmouth Hitchcock Medical Center
  • Montefiore Medical Center
  • Columbia University Medical Center
  • Duke University Medical Center
  • Cone Health Cancer Center
  • Oncology Hematology in Cincinnati
  • University of Cincinnati Cancer Institute
  • Cleveland Clinic
  • Ohio State University Medical Center
  • Providence Portland Medical Center
  • The Pennsylvania State University-Penn State
  • Thomas Jefferson University
  • The West Clinic
  • Sarah Cannon Research Institute
  • University of Texas Southwestern Medical Center
  • Virginia Cancer Specialists
  • Swedish Cancer Institute
  • University of Washington Medical Center
  • University of Wisconsin-Carbone Cancer Center
  • Atlantic Clinical Cancer Research Unit
  • McGill University Health Center
  • Institut Universitaire de Cardiologie et de Pneumologie De Quebec
  • Princess Margaret Hospital
  • Cancer Care Manitoba
  • Centre Hospitalier Regional Universitaire Besancon
  • CHU de Caen-Hopital Cote de Nacre
  • Hopital Saint Antoine
  • Centre Hospitalier de Grenoble
  • CHRU de Lille
  • Institut Paoli-Calmettes
  • Hopital Tenon
  • Centre Hospitalier Lyon Sud
  • CHU Toulouse-Hopital Larrey
  • Institut Gustave Roussy
  • Chungbuk National University Hospital
  • The Catholic University of Korea, St. Vincent's Hospital
  • Chonnam National University Hwasun Hospital
  • National Cancer Center
  • Seoul National University Bundang Hospital
  • Severance Hospital, Yonsei University Health System
  • Samsung Medical Center
  • Asan Medical Center
  • Hospital Germans Trias i Pujol
  • Hospital Universitari Quiron Dexeus Barcelona
  • Centro Integral Oncologico Clara Campal
  • Hospital Regional Universitario de Malaga

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

AT13387 and Crizotinib

Crizotinib versus crizotinib + AT13387

AT13387 or AT13387 + crizotinib

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.
- Number of patients with adverse events
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
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

Secondary Outcome Measures

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
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
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
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

Full Information

First Posted
October 11, 2012
Last Updated
January 17, 2018
Sponsor
Astex Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01712217
Brief Title
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
May 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer(NSCLC)
Keywords
Non-small cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AT13387 and Crizotinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Crizotinib versus crizotinib + AT13387
Arm Type
Active Comparator
Arm Description
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.
Arm Title
AT13387 or AT13387 + crizotinib
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AT13387
Intervention Description
HSP90 inhibitor
Intervention Type
Drug
Intervention Name(s)
Crizotinib
Other Intervention Name(s)
Xalkori
Intervention Description
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Primary Outcome Measure Information:
Title
Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.
Description
- Number of patients with adverse events
Time Frame
12 months
Title
Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.
Description
- Change in tumor measurements by RECIST 1.1 every 8 weeks
Time Frame
18 months
Title
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.
Description
- Change in tumor measurements by RECIST 1.1 every 8 weeks
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib
Description
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
Time Frame
12 months
Title
Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).
Description
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
Time Frame
12 months
Title
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
Description
Number of patients with adverse events PFS and OS as measured in weeks Response rate as measured by RECIST 1.1 every 8 weeks
Time Frame
18 months
Title
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
Description
Number of patients with adverse events PFS and OS as measured in weeks
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Charles Soria, MD
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic-Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California, San Diego Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0698
Country
United States
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Sharp Clinical Oncology Research-Sharp Memorial Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University School of Medicine-Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Florida Hospital Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
Facility Name
Northwestern University The Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Melvin and and Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic-Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center Eppley Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cone Health Cancer Center
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27409
Country
United States
Facility Name
Oncology Hematology in Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
The Pennsylvania State University-Penn State
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
The West Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Wisconsin-Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53579
Country
United States
Facility Name
Atlantic Clinical Cancer Research Unit
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
McGill University Health Center
City
Montreal, Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
City
Sainte-Foy, Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto, Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Cancer Care Manitoba
City
Winnipeg
ZIP/Postal Code
R3E OV9
Country
Canada
Facility Name
Centre Hospitalier Regional Universitaire Besancon
City
Besancon Cedex
ZIP/Postal Code
25030
Country
France
Facility Name
CHU de Caen-Hopital Cote de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Hopital Saint Antoine
City
Creteil Cedex
ZIP/Postal Code
94010
Country
France
Facility Name
Centre Hospitalier de Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHRU de Lille
City
Lille cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Hopital Tenon
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Benite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
CHU Toulouse-Hopital Larrey
City
Toulouse
ZIP/Postal Code
31 059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Chungbuk National University Hospital
City
Cheongju-si
ZIP/Postal Code
362-711
Country
Korea, Republic of
Facility Name
The Catholic University of Korea, St. Vincent's Hospital
City
Gyeonggi-do
ZIP/Postal Code
442-723
Country
Korea, Republic of
Facility Name
Chonnam National University Hwasun Hospital
City
Hwasun-gun Jeonnam
ZIP/Postal Code
519-809
Country
Korea, Republic of
Facility Name
National Cancer Center
City
Korea
ZIP/Postal Code
410-769
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
ZIP/Postal Code
463-707
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Universitari Quiron Dexeus Barcelona
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
Centro Integral Oncologico Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
ZIP/Postal Code
29010
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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