A Phase 2 Trial of Ponatinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

NCT01874665 | Completed Phase 2 Results

• 1 other identifier: AP24534-12-202
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ponatinib in participants with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) following failure of prior tyrosine kinase inhibitor (TKI) therapy.

Conditions

GIST

Keywords

Gastrointestinal Neoplasms; Gastrointestinal stromal tumor; mesenchymal tumor

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) in Cohort A

  To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting \>=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis \<10millimeter \[mm\]).No new lesions.PR is \>=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is \>=20% increase from the smallest prior sum of the longest diameter(SLD)and with \>=5mm absolute increase, or appearance of a new lesion.

  16 weeks after first dose

Secondary Outcomes (11)

• Clinical Benefit Rate (CBR) in Cohort B

  16 weeks after first dose

• Progression-free Survival (PFS)

  From date of enrollment until the end of the study or disease progression or death due to any cause, whichever came first, assessed up to 3 years

• Percentage of Participants With Objective Response Rate (ORR)

  From date of enrollment until discontinuation or the end of the study, whichever came first, assessed up to 3 years

• Overall Survival (OS)

  From first dose of drug until the end of the study or death, whichever came first, assessed up to 3 years

• Number of Participants With Physical Examination

  From date of enrollment until the End-of-Treatment, assessed up to 3 years

Study Arms (2)

Cohort A

EXPERIMENTAL

Participants with KIT exon 11-mutant GIST.

Drug: Ponatinib

Cohort B

EXPERIMENTAL

Participants with GIST that lack KIT exon 11 mutations (Cohort B).

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib 45 mg, tablets, orally, once-daily.

Also known as: AP24534, Iclusig

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Male or female participants \>=18 years old.
• GIST with failure of prior TKI therapy defined as:
• Histologically confirmed metastatic and/or unresectable GIST after experiencing failure of prior treatment with imatinib, sunitinib, and regorafenib. If prior TKI treatment was neoadjuvant therapy, then relapse must have occurred during the neoadjuvant therapy in order to consider it failed therapy.
• Participants in Cohort A must have evidence of activation mutations in exon 11 of KIT in their tumors. Demonstration of an exon 11 mutation may be based on prior assessment or on evaluation of a tumor sample after enrollment in this study. Participants in Cohort B must have GIST that lacks activating mutations in KIT exon 11, but may have evidence of another activating mutation such as in KIT exon 9 or in PDGFR-α. Participants may be enrolled in the study prior to determination of the appropriate cohort (as long as both cohorts are open for enrollment).
• Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Adequate hepatic function as defined by the following criteria:
• Total serum bilirubin less than or equal to (\<=) 1.5\*Upper Limit of Normal (ULN), unless due to Gilbert's syndrome.
• ALT \<=2.5\*ULN or \<=5.0\*ULN if liver metastases are present.
• AST \<=2.5\*ULN or \<=5.0\*ULN if liver metastases are present.
• Adequate renal function as defined by the following criterion:
• a. Serum creatinine \<1.5\*ULN.
• Adequate pancreatic function as defined by the following criterion:
• a. Serum lipase and amylase \<=1.5\*ULN.
• For participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.

You may not qualify if:

• Major surgery within 28 days prior to initiating therapy
• History of bleeding disorder
• History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
• History of alcohol abuse
• Uncontrolled hypertriglyceridemia (triglycerides \>450 milligram per deciliter \[mg/dL\])
• Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Any history of myocardial infarction (MI).
• Any history of unstable angina.
• Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment.
• History of clinically significant (as determined by the treating physician) atrial arrhythmia.
• Any history of ventricular arrhythmia.
• Any history of cerebrovascular accident or transient ischemic attack (TIA).
• Any history of peripheral vascular infarction, including visceral infarction; or any revascularization procedure of any vasculature, including the placement of a stent.
• Venous thromboembolism including deep venous thrombosis (DVT) or pulmonary embolism within 6 months prior to enrollment.
• Uncontrolled hypertension (diastolic blood pressure greater than (\>) 90 millimeter of mercury \[mmHg\]; systolic \>150 mmHg). Participants with hypertension should be under treatment on study entry to effect blood pressure control.

Sponsors & Collaborators

• Ariad Pharmaceuticals: lead

Study Sites (4)

Massachusetts General Hospital, Site #047

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute, Site #008

Boston, Massachusetts, 02215, United States

Location

Oregon Health & Sciences University, Site #048

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center, Site #012

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Limitations and Caveats

Study is ongoing. Uncontrolled Study. Small participant population. Non-randomized.

Results Point of Contact

• Title: Medical Director
• Organization: Ariad Pharmaceuticals

globaloncologymedinfo@takeda.com

+1-844-662-8532

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2013
• First Posted: June 11, 2013
• Study Start: June 5, 2013
• Primary Completion: February 28, 2015
• Study Completion: July 31, 2016
• Last Updated: May 18, 2018
• Results First Posted: May 17, 2016

Record last verified: 2018-04

Locations

US (4)