Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

A Prospective, Double Blind, Randomized, Placebo-Controlled Phase III Trial of Imatinib Re-Challenge in Patients With Gastrointestinal Stromal Tumor Who Had Benefit From Prior Imatinib But Progression From Both Imatinib and Sunitinib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01151852
• Other study ID #: AMC1001
• Status: Completed
• Phase: Phase 3
• Start date: June 2010
• Est. completion date: March 2013

Study information

• Verified date: January 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following failure of prior imatinib and sunitinib therapies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 18 years and older

• Patients with metastatic or unresectable malignant gastrointestinal stromal tumour which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRa genes on direct sequencing of tumor DNA.

• Prior benefit from 1st line imatinib defined as complete response, partial response, or stable disease at 6 months after the start of 1st line imatinib

• Patients whose disease has progressed despite at least both prior imatinib therapy (400mg/day) and then subsequently also failure of prior sunitinib therapy.

• ECOG(Eastern Cooperative Oncology Group) performance status 0 ~ 3

• Adequate bone marrow function as defined by platelets = 75 x 109/L and neutrophils = 1.5 x 109/L

• Adequate renal function, with serum creatinine < 1.5 x upper limit of normal

• Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase < 2.5 x upper limit of normal in the absence of liver metastases, or < 5 x upper limit of normal in the presence of liver metastases.

• Expected life expectancy of greater than 12 weeks in the absence of any intervention

• No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse

• Written, informed consent to the study

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non- compliance

• Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy

• Obstruction of gastrointestinal tract

• Active gastrointestinal bleeding

• Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)

• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol

• Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Imatinib
Patients will be randomly assigned to receive imatinib at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression, unacceptable toxicity, or withdrawal of consent.
• Placebo
Patients will be randomly assigned to receive placebo at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression or withdrawal of consent.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul	Songpa-gu

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004 Sep 15;22(18):3813-25. Review. — View Citation

De Giorgi U, Verweij J. Imatinib and gastrointestinal stromal tumors: Where do we go from here? Mol Cancer Ther. 2005 Mar;4(3):495-501. Review. — View Citation

Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006 May;42(8):1093-103. Epub 2006 Apr 18. — View Citation

Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. — View Citation

Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. — View Citation

Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003 Dec 1;21(23):4342-9. — View Citation

Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	To compare the progression free survival (PFS) assessed by the blinded independent central review following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with unresectable or metastatic GIST following failure of at least prior imatinib and sunitinib therapies	up tp12 weeks
Secondary	Disease Control Rate	Inclusion of complete response, partial response or stable disease; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Progressive disease (PD), >20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), Insufficient change to qualify for PR or PD.	up to 12 weeks
Secondary	Progression Free Survival	To compare PFS assessed by investigators	up to 12 weeks
Secondary	Response Rate	Tumour responses were initially determined by the local investigators in accordance with RECIST 1.0.Treatment decisions were based on local onsite radiological review. All imaging data were subsequently collected, anonymised, and reviewed centrally in a double-blind manner by two external academic radiology reviewers.; Response assessment was determined in a masked central review by use of RECIST1.1.	Up to 12weeks
Secondary	Overall Survival(OS) and Time to Progression(TTP)	To compare the overall survival (OS) and time to progression (TTP) in both arms of the study	Up to 3years
Secondary	Safety and Tolerability of Imatinib	percentage of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of imatinib re-challenge in this patient population	Up to 3years