Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib (ENEST)

Novartis

Status and phase: Completed; Phase 3

Conditions: Gastrointestinal Stromal Tumors

Treatments: Other: Best Supportive Care (BSC) +/- imatinib or sunitinib; Drug: Nilotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00471328

2006-002267-11 (EudraCT Number)

CAMN107A2201

Details and patient eligibility

About

The study evaluated the safety and efficacy of nilotinib versus current treatment in adults with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant to the first and second line treatments.

Enrollment: 248 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria (Core Phase):

• Age ≥18 years
• Radiological confirmation of disease progression during imatinib and sunitinib therapy OR intolerance to imatinib and/or sunitinib
• At least one measurable site of disease on CT/MRI scan
• Physically fit even if not able to work
• Normal organ, electrolyte, and bone marrow function

Inclusion criteria (Extension Phase):

• Patients whose tumors had progressed on the control arm and had crossed over to the nilotinib arm.
• The study was stopped due to meeting the primary efficacy endpoint of PFS at the interim analysis.
• Patients who were still being treated at the close of the Core study on the control arm or nilotinib arm (whose tumors have not progressed at the time of the end of the Core study).
• Patients must have had documented, confirmed stable, partial or complete response as defined by the RECIST criteria at the time of entry into the Extension study with the exception of patients who had progressed on the control arm.

Exclusion criteria (Core Phase):

• Previous treatment with nilotinib or any other drug in this class or other targeted therapy
• Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks prior to study entry
• Impaired cardiac function
• Use of coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
• Women who are pregnant or lactating

Exclusion criteria (Extension Phase):

• Use of other anticancer treatments or investigational drugs (with exception of the study drugs)
• Patients with a history of noncompliance with study drug treatment in the Core study protocol.

Other protocol-defined inclusion/exclusion criteria applied

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

248 participants in 2 patient groups

Nilotinib

Experimental group

Description:

400mg twice daily in core and extension phases of the study.

Treatment:

Drug: Nilotinib

Control/cross-over to Nilotinib

Active Comparator group

Description:

In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm. Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.

Treatment:

Drug: Nilotinib

Other: Best Supportive Care (BSC) +/- imatinib or sunitinib