A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib
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| ClinicalTrials.gov Identifier: NCT01712217 |
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Recruitment Status :
Completed
First Posted : October 23, 2012
Last Update Posted : January 19, 2018
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Sponsor:
Astex Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-small Cell Lung Cancer(NSCLC) | Drug: AT13387 Drug: Crizotinib | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 220 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 Start Date : | October 2012 |
| Actual Primary Completion Date : | December 2016 |
| Actual Study Completion Date : | May 16, 2017 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
Drug Information available for:
Crizotinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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Drug: AT13387
HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori |
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Active Comparator: 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.
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Drug: AT13387
HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori |
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Active Comparator: 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.
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Drug: AT13387
HSP90 inhibitor Drug: Crizotinib ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori |
Primary Outcome Measures :
- Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. [ Time Frame: 12 months ]- 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. [ Time Frame: 18 months ]- 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. [ Time Frame: 18 months ]- Change in tumor measurements by RECIST 1.1 every 8 weeks
Secondary Outcome Measures :
- Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib [ Time Frame: 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 4
- Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS). [ Time Frame: 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
- 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 [ Time Frame: 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 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 [ Time Frame: 18 months ]
- Number of patients with adverse events
- PFS and OS as measured in weeks
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01712217
Locations
Show 65 study locations
Sponsors and Collaborators
Astex Pharmaceuticals, Inc.
Investigators
| Principal Investigator: | Jean-Charles Soria, MD | Gustave Roussy, Cancer Campus, Grand Paris |
| Responsible Party: | Astex Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT01712217 |
| Other Study ID Numbers: |
AT13387-05 2012-001575-37 ( EudraCT Number ) |
| First Posted: | October 23, 2012 Key Record Dates |
| Last Update Posted: | January 19, 2018 |
| Last Verified: | January 2018 |
Keywords provided by Astex Pharmaceuticals, Inc.:
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Non-small cell lung cancer |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Crizotinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |