Ponatinib in Advanced NSCLC w/ RET Translocations

NCT01813734 | Completed Phase 2 Results DMC

• 1 other identifier: 13-103
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

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. It has been found that some people with NSCLC have a change (mutation) in a certain gene called the RET gene. This mutated gene may help cancer cells grow. Only participants with a RET mutation will be allowed to participate. In this study, investigators are testing the strategy of using a study drug designed to inhibit or shut off growth signals that results from the mutated RET gene. Ponatinib is an anti-cancer drug that has been used in research studies for other types of cancer. Ponatinib blocks several growth signals in cancer cells, including RET. In this research study, investigators are looking to see whether ponatinib is effective and safe in treating NSCLC harboring RET rearrangements.

Conditions

Non Small Cell Lung Cancer

Keywords

RET gene mutation

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The number of participants that achieved either a partial or complete response assessed using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) * 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.

  From the start of treatment until disease progression or death, up to approximately 2 years

Secondary Outcomes (4)

• Disease Control Rate

  From the start of treatment until disease progression or death, up to approximately 2 years

• Median Progression-Free Survival

  From study entry until disease progression or death, median duration of 3.8 months

• 1 Year Overall Survival Rate

  1 year

• Number of Participants With Adverse Events

  From the start of treatment until 30 days after the end of treatment (up to approximately 2 years)

Study Arms (1)

Ponatinib Treatment Arm

EXPERIMENTAL

Ponatinib 30 mg PO daily

Drug: Ponatinib

Interventions

Ponatinib DRUG

28 day cycle

Ponatinib Treatment Arm

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
• Molecular confirmation of a RET translocation
• At least one measurable lesion as defined by RECIST
• No restriction on number of prior therapies
• Estimated life expectancy of at least 12 weeks
• Able to swallow and retain orally administered medication
• Must agree to use an effective form of contraception from enrollment through 30 days after the end of study treatment
• Willingness and ability to comply with scheduled visits and study procedures

You may not qualify if:

• Clinically significant gastrointestinal abnormalities
• Pregnant or breastfeeding
• Major surgery within 28 days of initiating therapy
• History of CNS disease (Note: Participants with brain metastases will be eligible if treated appropriately and if they remain clinically stable).
• Anti-cancer therapy within 3 weeks
• History of significant bleeding disorder unrelated to cancer
• History of acute pancreatitis within 1 year of study entry or history of chronic pancreatitis
• History of alcohol abuse
• Uncontrolled hypertriglyceridemia
• History of arterial thrombotic events (myocardial infarction, stroke or peripheral vascular disease).
• Uncontrolled hypertension
• Taking medications that are known to be associated with Torsades de Pointes
• Ongoing active infection
• Diagnosed with or received anti-cancer therapy for another primary malignancy within 3 years prior to entry (except for non-melanoma skin cancer or in situ cancers)
• Any condition or illness tha could compromise patient safety or interfere with the evaluation of the drug

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (5)

University of California, Irvine

Orange, California, 92868, United States

Location

University of Maryland

Baltimore, Maryland, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.

  PMID: 26291023 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ponatinib

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: Dr. Alice Shaw
• Organization: Massachusetts General Hospital

ASHAW1@mgh.harvard.edu

617-724-4000

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: March 13, 2013
• First Posted: March 19, 2013
• Study Start: September 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: August 1, 2018
• Last Updated: December 24, 2019
• Results First Posted: December 24, 2019

Record last verified: 2019-12

Locations

US (5)