AUY922 for Advanced ALK-positive NSCLC

NCT01752400 | Completed Phase 2 Results DMC

• 1 other identifier: 12-458
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause and if the drug is effective for treating your type of cancer. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies. It has been found that some people with NSCLC have a change (mutation) in a certain gene called the ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib) that has been approved by the FDA for the treatment of people with NSCLC who have mutations in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients may stop responding (become resistant) to crizotinib because of additional changes in the ALK gene that makes crizotinib ineffective. AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells that have become resistant to drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to participate in this study. The purpose of this study is to test the safety of AUY922 and determine how well AUY922 treats participants with advanced, ALK-positive NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

Advanced

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The number of participants that achieved either a complete response (CR) or a partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \< 10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Baseline and then every six weeks (± 7 days), until the time of disease progression

Secondary Outcomes (7)

• Progression-free Survival

  From the start of treatment until the time of death or progression

• Disease Control Rate

  Baseline and then every six weeks (± 7 days), until the time of disease progression

• Number of Participants Who Develop Adverse Events on AUY922

  From the start of treatment until 30 days after last dose was received

• Number of Participants With Concurrent KRAS Mutations

  Baseline

• ALK Translocation Variant Type

  Baseline

Study Arms (1)

AUY922

EXPERIMENTAL

Via intravenous infusion on Days 1, 8 and 15 of each 21 day cycle (once per week). Infusion lasts approximately 60 minutes

Drug: AUY922

Interventions

AUY922 DRUG

AUY922

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed advanced NSCLC
• Tumor characterized by abnormalities in ALK
• Required to provide archival tissue in the form of 5 formalin fixed paraffin embedded sections
• Have acquired resistance to treatment with an ALK-TKI
• At least one measurable lesion as defined by RECIST criteria
• Life expectancy of at least 12 weeks

You may not qualify if:

• Pregnant or breastfeeding
• Discontinued ALK TKI more than four weeks prior to enrollment
• Unresolved diarrhea greater than or equal to CTCAE grade 1
• Not willing to use double barrier methods of contraception
• Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound
• Have received cytoxic chemotherapy in the intervening period since discontinuation of an ALK-TKI
• Have undergone major surgery within 2 weeks prior to starting study drug
• Any concurrent or uncontrolled illness
• Any known disorders due to a deficiency in bilirubin glucuronidation
• Taking therapeutic doses of warfarin
• Any serious cardiac disorders or abnormalities
• Concurrent malignancies or invasive cancers diagnosed within the past 2 years except for adequately treated basal cell cancer of the skin or in situ cancers
• Known to be HIV positive
• Known hypersensitivity to any of the study drugs or their excipients
• Participation in another clinical study within 30 days before the first study treatment

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Isreal Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Alice Shaw, MD, PhD
• Organization: Massachusetts General Hospital

ashaw1@mgh.harvard.edu

617-724-4000

Study Officials

• Alice Shaw, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 7, 2012
• First Posted: December 19, 2012
• Study Start: January 1, 2013
• Primary Completion: June 1, 2017
• Study Completion: November 1, 2017
• Last Updated: March 29, 2018
• Results First Posted: March 29, 2018

Record last verified: 2018-03

Locations

US (4)