Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

NCT01089595 | Terminated Phase 2 Results DMC

• 1 other identifier: FER-SAR-023
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

Patients with advanced GIST are treated with imatinib. This study seeks to look at a new therapeutic agent at the time of tumor progression following treatment with 600-800 mg daily of imatinib. The study is looking to see if Nilotinib (tasigna) alone or in combination with imatinib (gleevec) is more effective at controlling disease.

Conditions

GIST; Metastatic Disease

Keywords

Imatinib Resistance; GIST; Advanced Disease; Nilotinib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. It will be determined for both RECIST (Response Evaluation Criteria in Solid Tumors) and CHOI criteria.

  6 months until death or for 5 years

Secondary Outcomes (1)

• Best Overall Response Using Response Evaluation Criteria in Solid Tumors, Choi Criteria, and Positron Emission Tomography Imaging

  Every 8 weeks for up to 5 years

Study Arms (2)

Nilotinib

ACTIVE COMPARATOR

Nilotinib 400 mg po bid

Drug: Nilotinib

Nilotinib + Imatinib

ACTIVE COMPARATOR

Nilotinib 400 mg BID with Imatinib 400 mg daily

Drug: Nilotinib with Imatinib

Interventions

Nilotinib DRUG

Nilotinib 400 mg po bid

Also known as: Tasigna

Nilotinib

Nilotinib with Imatinib DRUG

Nilotinib 400 mg po BID Imatinib 400 mg po daily

Also known as: Tasigna, Gleevec

Nilotinib + Imatinib

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 GIST.
• advanced/metastatic GIST.
• experienced failure of prior treatment with imatinib 600-800 mg per day defined by progression of disease according to RECIST criteria during treatment. Radiographic evidence of PD on imatinib must be confirmed by the Investigator prior to enrollment.
• May have focal progression of disease including a new enhancing nodular focus within a pre-existing tumor nodule; such a nodule should be considered measurable by standard RECIST criteria.
• measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• At least 4 weeks since prior therapy with imatinib \& resolution of all acute toxic effects of the prior therapy or surgical procedure to grade ≤1.
• Age \>18 years.
• ECOG performance status 0-2.
• Normal organ and marrow function as defined below:
• ANC \>1,500/mcL
• Platelets \>100,000/mcL
• Total bilirubin \< or equal to 1.5 X ULN
• AST(SGOT)/ALT(SGPT) \< or equal to 2.5 X ULN OR \< or equal to 5.0 X ULN if considered due to tumor
• Amylase/Lipase \< or equal to 1.5 X ULN
• Alkaline Phosphatase \< or equal to 2.5 X ULN or \</= 5 X ULN if considered tumor related.

You may not qualify if:

• Have received nilotinib or additional tyrosine kinase inhibitors or additional targeted therapies (except for imatinib).
• May not be receiving any other investigational agents within 4 weeks before treatment.
• Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with exception of previous or concomitant basal cell skin, previous cervical carcinoma in situ.
• Impaired cardiac function, including any one of the following:
• Complete left bundle branch block. Ventricular paced cardiac pacemaker. Congenital long QT syndrome or family history of long QT syndrome. History of or presence of symptomatic ventricular or atrial tachyarrhythmias. Clinically significant resting bradycardia (\< 50 beats per minute). QTc \> 480 msec on screening ECG (using the QTcF formula). If QTc \> 480 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc).
• Right bundle branch block plus left anterior hemiblock, bifascicular block. Myocardial infarction within 12 months prior to Visit 1. Other clinically significant heart diseases (e.g., unstable angina, congestive heart failure or uncontrolled hypertension).
• Severe and/or uncontrolled concurrent medical disease that could cause unacceptable safety risks or compromise compliance with protocol e.g. impairment of GI function, or GI disease that may significantly alter absorption of study drugs; uncontrolled diabetes; active infections; psychiatric illness/social situation that would limit compliance with study requirements.
• Inability to remain laying down in PET scanner for up to one hour.
• Use of any medications that prolong the QT interval and CYP3A4 inhibitors if treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration.
• Major surgery ≤ 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery.
• Known history of noncompliance to medical regimens or inability/unwillingness to return for scheduled visits, patients who are pregnant or breast feeding, patients unwilling or unable to comply with the requirements for the protocol.
• Known chronic liver disease (i.e., chronic active, hepatitis, and cirrhosis).
• Known diagnosis of HIV, currently taking combination antiretroviral therapy.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Novartis: collaborator

Study Sites (3)

Siteman Cancer Center, Washington University School of Mediciine

St Louis, Missouri, 63110, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

nilotinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Trial ended early due to industry support of provision of nilotinib was discontinued.

Results Point of Contact

• Title: Margaret von Mehren, Principal Investigator
• Organization: Fox Chase Cancer Center

margaret.vonmehren@fccc.edu

215-728-4300

Study Officials

• Margaret von Mehren, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: March 18, 2010
• Study Start: February 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: March 1, 2012
• Last Updated: March 15, 2017
• Results First Posted: March 15, 2017

Record last verified: 2017-01

Locations

US (3)