Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

AT13387

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

Jean-Charles Soria, MD

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.

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.

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

A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

- Change in tumor measurements by RECIST 1.1 every 8 weeks

* 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

* 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

* Number of patients with adverse events
* PFS and OS as measured in weeks
* Response rate as measured by RECIST 1.1 every 8 weeks

* Number of patients with adverse events
* PFS and OS as measured in weeks

Astex Pharmaceuticals, Inc.

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Imatinib Mesylate

AT13387 administered on days 1, 8 and 15, imatinib administered daily

In part 1 pts will receive AT13387 in combination with imatinib. Up to 5 possible dose levels of AT13387 could be evaluated in combination with imatinib 400 mg daily: 120 mg/m2, 150 mg/m2, 180 mg/m2, 220 mg/m2 and 260 mg/m2. AT13387 IV (in the vein) on day 1, 8 and 15 of each 28 day cycle, until progression or unacceptable toxicity develops, in order to establish the recommended phase II combination dose, which will be used in part 2 and/or part 3 of the study.

In part 2 an additional 6-9pts will be treated.

In part 3, provided that sufficient evidence of anti-tumour effect was observed in part 2 (disease stabilisation or reduction in tumour dimensions by RECIST), then an additional 12pts will be treated with AT13387 in combination with imatinib. Alternatively, if combination treatment is found to have excellent efficacy the randomised phase of the study may start so that 12 pts receive AT13387 on its own (monotherapy) and 12 pts receive AT13387 in combination with imatinib.

AT13387 and Imatinib

George D Demetri, MD

The purpose of this study is to investigate if an investigational drug called AT13387 is active against Gastrointestinal Stromal Tumor (GIST) that is resistant to other treatments, and to understand more about the safety of AT13387.

Most subjects in the study will receive AT13387 along with another drug called imatinib (Gleevec). Imatinib is a standard (approved) drug for treating patients with GIST. Some patients may receive AT13387 on its own. As a result, we shall begin to understand the effects of AT13387 given on its own and when combined with imatinib.We shall also find out more about the side-effects of AT13387, and more about how the body breaks down (metabolizes) AT13387.

The study consists of 3 parts: Part 1 is a dose escalation phase, Part 2 is a dose expansion phase and Part 3 is either a further dose expansion phase or a randomised phase in which half the patients receive AT13387 monotherapy and half continue to receive AT13387 in combination with imatinib.

All patients will receive AT13387 given by intravenous infusion on Days 1, 8, and 15 of a 28-day cycle. Most patients will also receive imatinib 400 mg by mouth every day.

Patients will have tumour imaging at baseline, and at 2, 4 and 6 months, and then at 2 month intervals until cycle 12, and then 3-monthly thereafter.

Blood samples will be taken to measure plasma drug levels of AT13387 given in combination with imatinib

A Study to Investigate the Safety and Efficacy of AT13387, Alone or in Combination With Imatinib, in Patients With GIST

An Open-Label, Randomised, Multi-Centre, Phase II Study to Investigate the Safety and Efficacy of AT13387, Either as Monotherapy or in Combination With Imatinib, in Patients With Unresectable and/or Metastatic Malignant GIST Whose Tumour Has Progressed Following Treatment With a Maximum of Three Tyrosine Kinase Inhibitors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib	NCT01712217	Non-small Cell ...	AT13387 Crizotinib	18 Years -	Astex Pharmaceuticals, Inc.
A Study to Investigate the Safety and Efficacy of AT13387, Alone or in Combination With Imatinib, in Patients With GIST	NCT01294202	Gastrointestina...	AT13387 and Ima...	18 Years -	Astex Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for at13387

Every month we try and update this database with for at13387 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for at13387

Every month we try and update this database with for at13387 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for at13387 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.