A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene

NCT00237185 | Completed Phase 2 Results

• 2 other identifiers: CSTI571B2222CSTI571B2222/E1
• Study Type: interventional
• Target: 148
• Locations: 3 countries
• Sites: 5

Brief Summary

In the core study, participants with unresectable or metastatic gastrointestinal stromal tumors expressing c-kit were treated with either 400 mg or 600 mg imatinib mesylate for 3 years. The 10 year extension study allowed participants, who successfully completed the core study, to continue study treatment with imatinib mesylate provided they still benefited from treatment and did not demonstrate safety concerns as per the investigator's opinion.

Conditions

Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)

Keywords

GIST; c-kit; imatinib mesylate

Outcome Measures

Primary Outcomes (2)

• Best Tumor Response (Core)

  Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.

  Month 36

• Best Tumor Response (Core + Extension)

  Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.

  Month 156

Secondary Outcomes (10)

• Overall Survival (Core)

  Date of first imatinib dose to the date of death during the core period, up to 36 months.

• Overall Survival (Core + Extension)

  Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.

• Duration of Response (Core)

  Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.

• Duration of Response (Core + Extension)

  Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months

• Progression Free Survival (PFS) (Core + Extension)

  Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.

Study Arms (2)

imatinib mesylate 400 mg

EXPERIMENTAL

400 mg once daily

Drug: Imatinib mesylate

imatinib mesylate 600 mg

EXPERIMENTAL

600 mg once daily

Drug: Imatinib mesylate

Interventions

Imatinib mesylate DRUG

Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day. Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.

Also known as: Glivec, Gleevec

imatinib mesylate 400 mg; imatinib mesylate 600 mg

Eligibility Criteria

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

You may qualify if:

• Men and non-pregnant women ≥18 years of age with the histopathologically documented diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of KIT (CD117) expression via immunohistochemical analysis of tumor sample was also required
• At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid Tumor Response Criteria, which had not been previously embolized or irradiated
• Performance status ≤3 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria, as well as a life expectancy ≥6 months and adequate end organ function defined as follows: Total bilirubin \<1.5 times upper limit of normal (ULN), aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) \<2.5 x ULN (or \<5 x ULN if hepatic metastases were present), creatinine \<1.5 x ULN, absolute neutrophil count (ANC) \>1.5 x 10\^9/L, platelet count \>100 x 10\^9/L

You may not qualify if:

• Patients with fewer than five years of disease-free survival from any other (non-GIST) malignancy except if the other malignancy was not currently clinically significant and did not require active intervention or if the other malignancy was a basal cell skin cancer or a cervical carcinoma in situ
• Patients with known brain metastases
• Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by the New York Heart Association Criteria, severe concomitant disease, acute or known chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection
• Chemotherapy or other investigational therapy within four weeks prior to study entry (six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to ≥25% of the bone marrow
• Inability to cooperate
• Major surgery within two weeks or exposure to other investigational agents within 28 days of entry into the study

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Dana Farber Cancer Institute Dept of Sarcoma Oncology

Boston, Massachusetts, 02115, United States

Location

Oregon Health Sciences University Dept. of Oregon Health Sci.

Portland, Oregon, 97201, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Novartis Investigative Site

Geelong, Victoria, 3220, Australia

Location

Novartis Investigative Site

Helsinki, FIN-00029, Finland

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Piebaldism

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

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

No safety data was collected in the extension.

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 9, 2005
• First Posted: October 12, 2005
• Study Start: June 1, 2000
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 19, 2014
• Results First Posted: July 15, 2014

Record last verified: 2014-08

Locations

US (3); AU (1); FI (1)