Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT

• Sponsor: Asan Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01151852
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: Imatinib; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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.; Other Names: Glivec
Placebo Comparator: 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [up tp12 weeks]

   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

Secondary Outcome Measures

1. Disease Control Rate [up to 12 weeks]

   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.

2. Progression Free Survival [up to 12 weeks]

   To compare PFS assessed by investigators

3. Response Rate [Up to 12weeks]

   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.

4. Overall Survival(OS) and Time to Progression(TTP) [Up to 3years]

   To compare the overall survival (OS) and time to progression (TTP) in both arms of the study

5. Safety and Tolerability of Imatinib [Up to 3years]

   percentage of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of imatinib re-challenge in this patient population

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 PDGFRα 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center	Seoul	Songpa-gu	Korea, Republic of	138-736

Sponsors and Collaborators

• Asan Medical Center

Investigators

• Principal Investigator: Yoon-Koo Kang, MD, PhD, Asan Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Yoon-Koo Kang, Study Principal Investigator, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT01151852
• Other Study ID Numbers: AMC1001
• First Posted: Jun 29, 2010
• Last Update Posted: Jan 14, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Yoon-Koo Kang, Study Principal Investigator, Asan Medical Center: Imatinib; Re-challenge
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Imatinib Mesylate

Study Results

Participant Flow

Recruitment Details	Between July 20, 2010, and Jan 17, 81 patients were enrolled in Asan Medical Center, Seoul, Korea.
Pre-assignment Detail	Randomization was done in a double-blind manner and stratified by performance status (0-1 vs 2-3) and by the number of previous lines of tyrosine-kinase inhibitor therapy (2 or less vs more than 2).

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	41	40
COMPLETED	41	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Imatinib	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	41	40	81
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 70.7%	25 62.5%	54 66.7%
>=65 years	12 29.3%	15 37.5%	27 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (10.4)	59.6 (10.6)	58.7 (10.5)
Sex: Female, Male (Count of Participants)
Female	12 29.3%	14 35%	26 32.1%
Male	29 70.7%	26 65%	55 67.9%
Region of Enrollment (participants) [Number]
Korea, Republic of	41 100%	40 100%	81 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	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
Time Frame	up tp12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Median (95% Confidence Interval) [Months]	1.8	0.9

2. Secondary Outcome

Title	Disease Control Rate
Description	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.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Number [percentage of participants]	32 78%	5 12.5%

3. Secondary Outcome

Title	Progression Free Survival
Description	To compare PFS assessed by investigators
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Median (95% Confidence Interval) [Months]	1.8	1.7

4. Secondary Outcome

Title	Response Rate
Description	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.
Time Frame	Up to 12weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Number [percentage of participants]	0 0%	0 0%

5. Secondary Outcome

Title	Overall Survival(OS) and Time to Progression(TTP)
Description	To compare the overall survival (OS) and time to progression (TTP) in both arms of the study
Time Frame	Up to 3years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Overall survival	8.2	7.5
Time to progression	1.8	0.9

6. Secondary Outcome

Title	Safety and Tolerability of Imatinib
Description	percentage of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of imatinib re-challenge in this patient population
Time Frame	Up to 3years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib	Placebo
Arm/Group Description	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.	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.
Measure Participants	41	40
Number [percentage of participants]	100 243.9%	98 245%

Adverse Events

Arm/Group Title	Imatinib		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Imatinib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Imatinib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		2/40 (5%)
Gastrointestinal disorders
Diarrhea	0/41 (0%)		1/40 (2.5%)
Vomiting	0/41 (0%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Edema	1/41 (2.4%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Imatinib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/41 (100%)		39/40 (97.5%)
Blood and lymphatic system disorders
Neutropenia	12/41 (29.3%)		5/40 (12.5%)
Anemia	27/41 (65.9%)		18/40 (45%)
Thrombocytopenia	8/41 (19.5%)		3/40 (7.5%)
Gastrointestinal disorders
Anorexia	14/41 (34.1%)		8/40 (20%)
Nausea	13/41 (31.7%)		1/40 (2.5%)
Vomiting	13/41 (31.7%)		2/40 (5%)
Constipation	6/41 (14.6%)		4/40 (10%)
Diarrhea	5/41 (12.2%)		4/40 (10%)
General disorders
Fatigue	15/41 (36.6%)		5/40 (12.5%)
Hepatobiliary disorders
Hyperbilirubinemia	10/41 (24.4%)		6/40 (15%)
Musculoskeletal and connective tissue disorders
Edema	18/41 (43.9%)		5/40 (12.5%)
Renal and urinary disorders
Azotemia	8/41 (19.5%)		4/40 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.