Trial Outcomes & Findings for Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST) (NCT NCT03556384)
NCT ID: NCT03556384
Last Updated: 2026-07-28
Results Overview
To determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: 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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
6 months
Results posted on
2026-07-28
Participant Flow
Participant milestones
| Measure |
TMZ 85 mg/m2 mg Orally
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Overall Study
STARTED
|
23
|
|
Overall Study
COMPLETED
|
23
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
Baseline characteristics by cohort
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 Participants
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Age, Continuous
|
42.43 years
STANDARD_DEVIATION 15.62 • n=20 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=20 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=20 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=20 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=20 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=20 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=20 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=20 Participants
|
|
Primary Tumor Site
|
23 Participants
n=20 Participants
|
PRIMARY outcome
Timeframe: 6 monthsTo determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: 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.
Outcome measures
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 Participants
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Overall Response Rate
|
2 participants
|
SECONDARY outcome
Timeframe: 30 monthsProgression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 Participants
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Progression-free Survival
|
16.5 months
Interval 6.2 to
Upper limit of the 95% confidence interval was not reached.
|
SECONDARY outcome
Timeframe: 40 monthsNumber of participants alive
Outcome measures
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 Participants
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Overall Survival
|
19 Participants
|
SECONDARY outcome
Timeframe: 40 monthsNumber of participants with adverse events and serious adverse events
Outcome measures
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 Participants
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Adverse Events and Serious Adverse Events
|
23 Participants
|
Adverse Events
TMZ 85 mg/m2 mg Orally
Serious events: 8 serious events
Other events: 23 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 participants at risk
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Blood and lymphatic system disorders
Platelet count decreased
|
13.0%
3/23 • Number of events 3 • 40 months
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23 • Number of events 1 • 40 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.3%
1/23 • Number of events 1 • 40 months
|
|
General disorders
Pain
|
4.3%
1/23 • Number of events 1 • 40 months
|
|
General disorders
Edema Limbs
|
4.3%
1/23 • Number of events 1 • 40 months
|
|
Infections and infestations
Sepsis
|
4.3%
1/23 • Number of events 1 • 40 months
|
|
General disorders
Flank Pain
|
4.3%
1/23 • Number of events 1 • 40 months
|
Other adverse events
| Measure |
TMZ 85 mg/m2 mg Orally
n=23 participants at risk
TMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection.
An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
Temozolomide: Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles.
Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
2/23 • 40 months
|
|
Metabolism and nutrition disorders
Dehydration
|
8.7%
2/23 • 40 months
|
|
Gastrointestinal disorders
Dry mouth
|
8.7%
2/23 • 40 months
|
|
General disorders
Fall
|
8.7%
2/23 • 40 months
|
|
Blood and lymphatic system disorders
Hemoglobin increased
|
8.7%
2/23 • 40 months
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
8.7%
2/23 • 40 months
|
|
Cardiac disorders
Hypertension
|
8.7%
2/23 • 40 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
8.7%
2/23 • 40 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
8.7%
2/23 • 40 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
8.7%
2/23 • 40 months
|
|
Psychiatric disorders
Insomnia
|
8.7%
2/23 • 40 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
8.7%
2/23 • 40 months
|
|
Gastrointestinal disorders
Stomach pain
|
8.7%
2/23 • 40 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.0%
3/23 • 40 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
13.0%
3/23 • 40 months
|
|
General disorders
Edema limbs
|
13.0%
3/23 • 40 months
|
|
Nervous system disorders
Headache
|
13.0%
3/23 • 40 months
|
|
Endocrine disorders
Hyperglycemia
|
13.0%
3/23 • 40 months
|
|
Endocrine disorders
Hyperthyroidism
|
13.0%
3/23 • 40 months
|
|
General disorders
Fatigue
|
60.9%
14/23 • 40 months
|
|
Gastrointestinal disorders
Vomiting
|
60.9%
14/23 • 40 months
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
52.2%
12/23 • 40 months
|
|
Gastrointestinal disorders
Constipation
|
43.5%
10/23 • 40 months
|
|
Blood and lymphatic system disorders
Anemia
|
39.1%
9/23 • 40 months
|
|
Gastrointestinal disorders
Diarrhea
|
39.1%
9/23 • 40 months
|
|
Gastrointestinal disorders
Abdominal pain
|
34.8%
8/23 • 40 months
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
34.8%
8/23 • 40 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.7%
2/23 • 40 months
|
|
Psychiatric disorders
Anorexia
|
8.7%
2/23 • 40 months
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
26.1%
6/23 • 40 months
|
|
Hepatobiliary disorders
Alanine aminotransferase increased
|
21.7%
5/23 • 40 months
|
|
Nervous system disorders
Dizziness
|
21.7%
5/23 • 40 months
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
21.7%
5/23 • 40 months
|
|
Psychiatric disorders
Anxiety
|
17.4%
4/23 • 40 months
|
|
General disorders
Pain
|
17.4%
4/23 • 40 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
17.4%
4/23 • 40 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
17.4%
4/23 • 40 months
|
|
Hepatobiliary disorders
Aspartate aminotransferase increased
|
13.0%
3/23 • 40 months
|
|
Investigations
CPK increased
|
13.0%
3/23 • 40 months
|
|
Gastrointestinal disorders
Nausea
|
73.9%
17/23 • 40 months
|
Additional Information
Adam Burgoyne, MD, PhD
University of California, San Diego
Phone: (858) 822-5354
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place