Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients

• Sponsor: Sarcoma Alliance for Research through Collaboration (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01031628
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 5
• Locations: 13
• Arms: 4
• Duration (Months): 17
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if escalating the dose of imatinib to keep the drug blood level at ≥ 1100 ng/ml leads to better outcomes for patients.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Phase 3 Study of Dose Escalation Versus No Dose Escalation of Imatinib In Metastatic GIST Patients With Imatinib Trough Levels Less Than 1100 Nanograms/mL
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A Patients with blood level less than 1100 will continue imatinib 400 mg daily	Drug: Imatinib mesylate; 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops; Other Names: Gleevec Glivec
Active Comparator: Arm B Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL	Drug: Imatinib mesylate; 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops; Other Names: Gleevec Glivec
Active Comparator: Arm C Patients with blood level ≥1100 will continue imatinib 400 mg daily	Drug: Imatinib mesylate; 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops; Other Names: Gleevec Glivec
Active Comparator: Arm D Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily	Drug: Imatinib mesylate; 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops; Other Names: Gleevec Glivec

Outcome Measures

Primary Outcome Measures

1. Evaluation of Lesions for Progression or Response Via RECIST Criteria [Every 3 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age ≥ 18 years

• Unresectable and/or metastatic GIST

• Currently receiving imatinib 400 mg per day for a minimum of 4 weeks prior to registration, and for no more than 6 months prior to registration. This must be the first time that the patient has been treated for metastatic and/or unresectable GIST

• For patients who received imatinib following surgery at the time of an initial diagnosis of GIST, there must be a 6 month interval between completion of imatinib and the diagnosis of metastatic GIST

• Good physical functioning (ECOG Performance Status of 0 or 1)

• Generally, good function of organ such as liver and kidneys

Exclusion Criteria:

• Disease progression during adjuvant therapy with imatinib (adjuvant treatment is treatment that is given after surgery for GIST)

• Known intolerance of imatinib at a dose of 400 mg/day or higher

• Prior systemic therapy for advanced GIST with imatinib or those who have been on imatinib for longer than 6 months for unresectable and/or metastatic disease

• Major surgery within 2 weeks prior to Day 1 of study or who have not yet recovered from prior surgery

• Use of coumadin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)

• Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks or who have not recovered from side effects of this therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Outpatient Cancer Center	Los Angeles	California	United States	90048
2	Sarcoma Oncology Center	Santa Monica	California	United States	90403
3	Washington Cancer Institute	Washington	District of Columbia	United States	20010
4	Northwestern University	Chicago	Illinois	United States	60622
5	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52246
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
9	Carolinas Hematology Oncology Associates	Charlotte	North Carolina	United States	28203
10	Duke University Medical Center	Durham	North Carolina	United States	27710
11	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
12	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
13	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Sarcoma Alliance for Research through Collaboration
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Suzanne George, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• SARC Website

Publications

None provided.

• Responsible Party: Sarcoma Alliance for Research through Collaboration
• ClinicalTrials.gov Identifier: NCT01031628
• Other Study ID Numbers: SARC019; STI571BUS286T
• First Posted: Dec 14, 2009
• Last Update Posted: Sep 9, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Sarcoma Alliance for Research through Collaboration: GIST; Gastrointestinal stromal tumors; Exon 9; Gleevec; Imatinib blood levels
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	400 mg for Patients With Imatinib Blood Levels < 1100	600 or 800 mg for Patients With Imatinib Blood Levels < 1100	400 mg for Patients With Imatinib Blood Levels ≥ 1100	400, 600 or 800 mg for Patients With Exon 9 Mutation Tumors
Arm/Group Description	Patients with imatinib trough blood levels less than 1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with imatinib trough blood levels less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL Imatinib mesylate : 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with imatinib trough blood levels ≥1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily Imatinib mesylate : 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops
Period Title: Overall Study
STARTED	0	1	3	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	1	3	0

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Arm C	Arm D	Total
Arm/Group Description	Patients with blood level less than 1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL Imatinib mesylate : 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with blood level ≥1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily Imatinib mesylate : 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Total of all reporting groups
Overall Participants	0	1	3	0	4
Age (participants) [Number]
<=18 years	0 NaN	0 0%	0 0%
Between 18 and 65 years	0 NaN	3 300%	3 100%
>=65 years	1 Infinity	0 0%	1 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71	56.7 (8.39)	60.25 (7.68)
Gender (participants) [Number]
Female	1 Infinity	1 100%	2 66.7%
Male	0 NaN	2 200%	2 66.7%
Region of Enrollment (participants) [Number]
United States	1 Infinity	3 300%	4 133.3%

Outcome Measures

1. Primary Outcome

Title	Evaluation of Lesions for Progression or Response Via RECIST Criteria
Time Frame	Every 3 months

Outcome Measure Data

Analysis Population Description

Data were not collected or analyzed due to early termination.

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Patients with blood level less than 1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL Imatinib mesylate : 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with blood level ≥1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops	Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily Imatinib mesylate : 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops
Measure Participants	0	0	0	0

Adverse Events

Arm/Group Title	Arm A		Arm B		Arm C		Arm D
Arm/Group Description	Patients with blood level less than 1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops		Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL Imatinib mesylate : 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops		Patients with blood level ≥1100 will continue imatinib 400 mg daily Imatinib mesylate : 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops		Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily Imatinib mesylate : 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops
All Cause Mortality
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)		0/3 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/1 (100%)		2/3 (66.7%)		0/0 (NaN)
Gastrointestinal disorders
Nausea	0/0 (NaN)	0	1/1 (100%)	2	1/3 (33.3%)	1	0/0 (NaN)	0
Diarrhea	0/0 (NaN)	0	0/1 (0%)	0	2/3 (66.7%)	2	0/0 (NaN)	0
General disorders
Fatigue	0/0 (NaN)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0
Pain	0/0 (NaN)	0	0/1 (0%)	0	1/3 (33.3%)	2	0/0 (NaN)	0
Infections and infestations
Skin Infection	0/0 (NaN)	0	1/1 (100%)	2	0/3 (0%)	0	0/0 (NaN)	0
Musculoskeletal and connective tissue disorders
Back Pain	0/0 (NaN)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0
Nervous system disorders
Dysguesia	0/0 (NaN)	0	1/1 (100%)	1	0/3 (0%)	0	0/0 (NaN)	0
Headache	0/0 (NaN)	0	1/1 (100%)	1	0/3 (0%)	0	0/0 (NaN)	0
Psychiatric disorders
Insomnia	0/0 (NaN)	0	1/1 (100%)	1	1/3 (33.3%)	1	0/0 (NaN)	0

Limitations/Caveats

A decision was made to discontinue the SARC019 trial effective March 3, 2011, due to lack of feasibility secondary to slow accrual. Due to early termination of the study, no patients were analyzed.

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.