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Trial Outcomes & Findings for TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer (NCT NCT04166435)

NCT ID: NCT04166435

Last Updated: 2023-09-06

Results Overview

To determine the efficacy of TMZ in combination with olaparib in subjects with MGMT promoter hypermethylated advanced colorectal cancer. The overall response rate (ORR) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) before and after treatment. Complete Response (CR): disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD). Clinical Benefit is defined as the sum of CR, PR, or SD post treatment from the start of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 1.5 years

Results posted on

2023-09-06

Participant Flow

Participant milestones

Participant milestones
Measure
Temozolomide + Olaparib
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Overall Study
STARTED
11
Overall Study
COMPLETED
9
Overall Study
NOT COMPLETED
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Temozolomide + Olaparib
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Overall Study
2 patients ineligible for response
2

Baseline Characteristics

TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Temozolomide + Olaparib
n=9 Participants
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Age, Customized
59 years
n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
Race/Ethnicity, Customized
White
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
1 Participants
n=5 Participants
Region of Enrollment
United States
9 participants
n=5 Participants
ECOG performance status
0-Fully active, able to carry on all pre-disease performance without restriction
3 Participants
n=5 Participants
ECOG performance status
1-No physically strenuous activity but ambulatory and can carry out light or sedentary activities
6 Participants
n=5 Participants
ECOG performance status
2-Capable of selfcare but can't carry out any work activities; up to about 50% of waking hours
0 Participants
n=5 Participants
ECOG performance status
3-Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
0 Participants
n=5 Participants
ECOG performance status
4-Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
0 Participants
n=5 Participants
ECOG performance status
5-Dead
0 Participants
n=5 Participants
Side of primary tumor
Left
4 Participants
n=5 Participants
Side of primary tumor
Right
5 Participants
n=5 Participants
Tumor Grade
Poorly differentiated
3 Participants
n=5 Participants
Tumor Grade
Moderately differentiated
6 Participants
n=5 Participants
Molecular Results
KRAS mutated
7 Participants
n=5 Participants
Molecular Results
KRAS/RAF wildtype
2 Participants
n=5 Participants
Number of prior therapies
2
2 Participants
n=5 Participants
Number of prior therapies
≥ 3
7 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 1.5 years

To determine the efficacy of TMZ in combination with olaparib in subjects with MGMT promoter hypermethylated advanced colorectal cancer. The overall response rate (ORR) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) before and after treatment. Complete Response (CR): disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD). Clinical Benefit is defined as the sum of CR, PR, or SD post treatment from the start of treatment.

Outcome measures

Outcome measures
Measure
Temozolomide + Olaparib
n=9 Participants
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Overall Response Rate
Complete Response
0 Participants
Overall Response Rate
Partial Response
0 Participants
Overall Response Rate
Stable Disease
5 Participants
Overall Response Rate
Progressive Disease
4 Participants

SECONDARY outcome

Timeframe: Up to 2 years from last treatment

To determine the safety of TMZ in combination with olaparib, the number of participants with ≥ grade 3 treatment related adverse events by CTCAE v5.0 coding will be assessed.

Outcome measures

Outcome measures
Measure
Temozolomide + Olaparib
n=9 Participants
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Count of Participants With Adverse Events Greater or Equal to 3
7 Participants

SECONDARY outcome

Timeframe: Up to 2 years from last treatment

To estimate the progression free survival (PFS), patients will be followed for up to 24 months.

Outcome measures

Outcome measures
Measure
Temozolomide + Olaparib
n=9 Participants
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Progression Free Survival
3 months
Interval 2.1 to
upper limit was not reached

SECONDARY outcome

Timeframe: Up to 2 years from last treatment

To estimate overall survival (OS), patients will be followed for up to 24 months.

Outcome measures

Outcome measures
Measure
Temozolomide + Olaparib
n=9 Participants
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Overall Survival
9.4 months
Interval 6.7 to
upper limit not reached

Adverse Events

Temozolomide + Olaparib

Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Temozolomide + Olaparib
n=9 participants at risk
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Gastrointestinal disorders
Nausea
11.1%
1/9 • Number of events 1 • up to 2 years

Other adverse events

Other adverse events
Measure
Temozolomide + Olaparib
n=9 participants at risk
Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle. Temozolomide + Olaparib: Temozolomide (75 mg/m2 orally on days 1-7 every 3 weeks) + Olaparib (150 mg orally twice daily days 1-21) in a 21-day cycle.
Gastrointestinal disorders
Nausea
33.3%
3/9 • up to 2 years
General disorders
Fatigue
22.2%
2/9 • up to 2 years
Metabolism and nutrition disorders
Anorexia
22.2%
2/9 • up to 2 years
Gastrointestinal disorders
Constipation
11.1%
1/9 • up to 2 years
Gastrointestinal disorders
Mucositis
11.1%
1/9 • up to 2 years
Investigations
White blood cell decreased
66.7%
6/9 • up to 2 years
Investigations
Neutrophil count decreased
55.6%
5/9 • up to 2 years
Investigations
Platelet count decreased
55.6%
5/9 • up to 2 years
Blood and lymphatic system disorders
Anemia
44.4%
4/9 • up to 2 years
Investigations
Lymphocyte count decreased
33.3%
3/9 • up to 2 years
Investigations
Aspartate aminotransferase increased
22.2%
2/9 • up to 2 years
Investigations
Alkaline phosphatase increased
11.1%
1/9 • up to 2 years

Additional Information

Dr. Michael Cecchini

Yale University

Phone: (203) 737-3472

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place