Trial Outcomes & Findings for Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status (NCT NCT00912743)
NCT ID: NCT00912743
Last Updated: 2016-11-09
Results Overview
Tumour response is the number of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 months
Results posted on
2016-11-09
Participant Flow
Target accrual: 54 subjects. MSI-H group: 15; non-MSI-H group: 39. Pre-planned interim analysis of the non-MSI-H cohort, after 17 patients, stopped recruitment into that cohort. Recruitment to the MSI-H cohort continued.
Subjects with stage IV, measurable disseminated CRC incurable by surgery, with tumour progression following standard combination front-line or second-line chemotherapy, relapsed or recurrent disease within 6 months completing adjuvant or neoadjuvant chemotherapy and met all inclusion/exlusion criteria.
Participant milestones
| Measure |
MSI-H
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
20
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
13
|
20
|
Reasons for withdrawal
| Measure |
MSI-H
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
9
|
18
|
|
Overall Study
Toxicity
|
0
|
1
|
|
Overall Study
End of treatment form was not collected
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Olaparib in Pretreated Patients With Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status
Baseline characteristics by cohort
| Measure |
MSI-H
n=13 Participants
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 Participants
Non-MSI-H group receiving olaparib 400mg BID
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.77 years
STANDARD_DEVIATION 9.37 • n=5 Participants
|
61.80 years
STANDARD_DEVIATION 11.46 • n=7 Participants
|
57.85 years
STANDARD_DEVIATION 11.65 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
10 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 monthsPopulation: Full analysis set - all treated patients
Tumour response is the number of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1)
Outcome measures
| Measure |
MSI-H
n=13 Participants
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 Participants
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Tumour Response
|
0 Percentage of Participants
Interval 0.0 to 25.0
|
0 Percentage of Participants
Interval 0.0 to 17.0
|
SECONDARY outcome
Timeframe: From baseline, i.e. up to 28 days before first study drug dose, and then every 2 cycles (8 weeks) up to objective disease progression by RECIST, assessed up to 35 monthsPopulation: Full analysis set - all treated patients
Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit.
Outcome measures
| Measure |
MSI-H
n=13 Participants
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 Participants
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Progression Free Survival
|
61 days
Interval 52.0 to 360.0
|
55 days
Interval 49.0 to 56.0
|
SECONDARY outcome
Timeframe: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed up to 35 monthsPopulation: Full analysis set - all treated patients
Overall survival is defined as the duration from first dose till death from any cause. In absence of death, the time is calculated from first dose till the date subject last known to be alive
Outcome measures
| Measure |
MSI-H
n=13 Participants
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 Participants
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Overall Survival
|
248 days
Interval 121.0 to 554.0
|
290.5 days
Interval 157.0 to 429.0
|
Adverse Events
MSI-H
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Non-MSI-H
Serious events: 3 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MSI-H
n=13 participants at risk
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 participants at risk
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.7%
1/13
|
0.00%
0/20
|
|
Cardiac disorders
Nodal rhythm
|
7.7%
1/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Ascites
|
7.7%
1/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
7.7%
1/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Intestinal obstruction
|
7.7%
1/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
15.4%
2/13
|
0.00%
0/20
|
|
General disorders
Mucosal inflammation
|
7.7%
1/13
|
0.00%
0/20
|
|
General disorders
Oedema peripheral
|
7.7%
1/13
|
0.00%
0/20
|
|
Infections and infestations
Urinary tract infection
|
7.7%
1/13
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Vena cava injury
|
7.7%
1/13
|
0.00%
0/20
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/13
|
5.0%
1/20
|
|
Nervous system disorders
Headache
|
0.00%
0/13
|
5.0%
1/20
|
|
Renal and urinary disorders
Hydronephrosis
|
15.4%
2/13
|
0.00%
0/20
|
|
Renal and urinary disorders
Renal failure acute
|
7.7%
1/13
|
0.00%
0/20
|
|
Renal and urinary disorders
Ureteric obstruction
|
7.7%
1/13
|
0.00%
0/20
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
7.7%
1/13
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13
|
0.00%
0/20
|
|
Vascular disorders
Deep vein thrombosis
|
7.7%
1/13
|
5.0%
1/20
|
Other adverse events
| Measure |
MSI-H
n=13 participants at risk
MSI-H group receiving olaparib 400mg BID
|
Non-MSI-H
n=20 participants at risk
Non-MSI-H group receiving olaparib 400mg BID
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
46.2%
6/13
|
35.0%
7/20
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.7%
1/13
|
15.0%
3/20
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.7%
1/13
|
20.0%
4/20
|
|
Gastrointestinal disorders
Abdominal pain
|
23.1%
3/13
|
20.0%
4/20
|
|
Gastrointestinal disorders
Constipation
|
38.5%
5/13
|
15.0%
3/20
|
|
Gastrointestinal disorders
Diarrhoea
|
15.4%
2/13
|
25.0%
5/20
|
|
Gastrointestinal disorders
Dyspepsia
|
15.4%
2/13
|
15.0%
3/20
|
|
Gastrointestinal disorders
Nausea
|
61.5%
8/13
|
75.0%
15/20
|
|
Gastrointestinal disorders
Vomiting
|
46.2%
6/13
|
45.0%
9/20
|
|
General disorders
Fatigue
|
38.5%
5/13
|
40.0%
8/20
|
|
General disorders
Oedema peripheral
|
15.4%
2/13
|
20.0%
4/20
|
|
Investigations
Blood creatinine increased
|
15.4%
2/13
|
10.0%
2/20
|
|
Investigations
Haemoglobin decreased
|
7.7%
1/13
|
15.0%
3/20
|
|
Metabolism and nutrition disorders
Anorexia
|
23.1%
3/13
|
25.0%
5/20
|
|
Nervous system disorders
Dizziness
|
23.1%
3/13
|
5.0%
1/20
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/13
|
20.0%
4/20
|
|
Nervous system disorders
Headache
|
15.4%
2/13
|
20.0%
4/20
|
|
Psychiatric disorders
Insomnia
|
15.4%
2/13
|
10.0%
2/20
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13
|
20.0%
4/20
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
1/13
|
15.0%
3/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
23.1%
3/13
|
15.0%
3/20
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.7%
1/13
|
5.0%
1/20
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/13
|
10.0%
2/20
|
|
Gastrointestinal disorders
Ascites
|
7.7%
1/13
|
5.0%
1/20
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
15.4%
2/13
|
0.00%
0/20
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/13
|
10.0%
2/20
|
|
General disorders
Chills
|
7.7%
1/13
|
10.0%
2/20
|
|
General disorders
Oedema
|
0.00%
0/13
|
10.0%
2/20
|
|
General disorders
Pyrexia
|
7.7%
1/13
|
10.0%
2/20
|
|
Infections and infestations
Urinary tract infection
|
7.7%
1/13
|
10.0%
2/20
|
|
Metabolism and nutrition disorders
Abnormal loss of weight
|
0.00%
0/13
|
10.0%
2/20
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.7%
1/13
|
5.0%
1/20
|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
1/13
|
10.0%
2/20
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
7.7%
1/13
|
5.0%
1/20
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
7.7%
1/13
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/13
|
10.0%
2/20
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/13
|
10.0%
2/20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/13
|
15.0%
3/20
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/13
|
10.0%
2/20
|
|
Nervous system disorders
Neuropathy peripheral
|
7.7%
1/13
|
5.0%
1/20
|
|
Psychiatric disorders
Anxiety
|
15.4%
2/13
|
0.00%
0/20
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/13
|
10.0%
2/20
|
|
Renal and urinary disorders
Hydronephrosis
|
23.1%
3/13
|
0.00%
0/20
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/13
|
10.0%
2/20
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
15.4%
2/13
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/13
|
10.0%
2/20
|
|
Vascular disorders
Deep vein thrombosis
|
7.7%
1/13
|
5.0%
1/20
|
Additional Information
Angela Sawyer, Clinical Delivery Director
Astra Zeneca LLP
Phone: +44 1625 512397
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60