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

Astex Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer(NSCLC)

Treatments: Drug: Crizotinib; Drug: AT13387

Study type: Interventional

Funder types: Industry

Identifiers

NCT01712217

2012-001575-37 (EudraCT Number)

AT13387-05

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 3 patient groups

AT13387 and Crizotinib

Experimental group

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.

Treatment:

Drug: AT13387

Drug: Crizotinib

Crizotinib versus crizotinib + AT13387

Active Comparator group

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.

Treatment:

Drug: AT13387

Drug: Crizotinib

AT13387 or AT13387 + crizotinib

Active Comparator group

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.

Treatment:

Drug: AT13387

Drug: Crizotinib