Colorectal Cancer
Conditions
Keywords
Colorectal cancer, Olaparib, MSI status, Stage IV, Measurable Colorectal Cancer, Stratified by MSI Status
Brief summary
This study is being carried out to see if the new drug, olaparib (AZD2281), can effectively and safely treat advanced large bowel cancer. The primary goal of this clinical trial is to determine whether olaparib will have a beneficial effect on the patient's cancer by causing a response and increasing the time it takes for the cancer to progress.
Interventions
DRUGolaparib
400 mg po bid continuously
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Patients will have measurable disseminated colorectal cancer that is incurable by surgery * Patients will have had tumor progression following standard combination front-line or second-line chemotherapy. * CRC patients who have relapsed or recurrent disease within six months after completing adjuvant or neoadjuvant chemotherapy
Exclusion criteria
* Previous treatment with PARP inhibitors, including olaparib. * Patients with symptomatic, uncontrolled brain metastases. * Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 4 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used). * Patients who are unable to swallow orally administered medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumour Response | 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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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 | 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. |
| Overall Survival | Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed up to 35 months | 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 |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| MSI-H MSI-H group receiving olaparib 400mg BID | 13 |
| Non-MSI-H Non-MSI-H group receiving olaparib 400mg BID | 20 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | End of treatment form was not collected | 1 | 0 |
| Overall Study | Lack of Efficacy | 9 | 18 |
| Overall Study | Toxicity | 0 | 1 |
Baseline characteristics
| Characteristic | Non-MSI-H | Total | MSI-H |
|---|---|---|---|
| Age, Continuous | 61.80 years STANDARD_DEVIATION 11.46 | 57.85 years STANDARD_DEVIATION 11.65 | 51.77 years STANDARD_DEVIATION 9.37 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 29 Participants | 10 Participants |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 13 | 20 / 20 |
| serious Total, serious adverse events | 6 / 13 | 3 / 20 |
Outcome results
Primary
Tumour Response
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)
Time frame: 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
Population: Full analysis set - all treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MSI-H | Tumour Response | 0 Percentage of Participants |
| Non-MSI-H | Tumour Response | 0 Percentage of Participants |
Secondary
Overall Survival
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
Time frame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed up to 35 months
Population: Full analysis set - all treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MSI-H | Overall Survival | 248 days |
| Non-MSI-H | Overall Survival | 290.5 days |
Secondary
Progression Free Survival
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.
Time frame: 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
Population: Full analysis set - all treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MSI-H | Progression Free Survival | 61 days |
| Non-MSI-H | Progression Free Survival | 55 days |