Trial Outcomes & Findings for OLAParib COmbinations (NCT NCT02576444)
NCT ID: NCT02576444
Last Updated: 2022-12-28
Results Overview
Tumor overall response rate (ORR) in molecularly selected patients with measurable disease as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), before versus after 16 weeks of treatment across tumor types in each arm of the study (Note: there will be no formal comparison between arms). 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 at 16 weeks from the start of treatment.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
67 participants
Primary outcome timeframe
Change from baseline to 16 weeks
Results posted on
2022-12-28
Participant Flow
Participant milestones
| Measure |
Olaparib AZD2881
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
Olaparib & Adavosertib AZD1775
Patients with tumors harboring mutations in HDR genes, including ATM, CHK2, APOBEC, MRE11 complex, will be treated with AZD6738 and olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD6738: Patients will be administered AZD6738 at 160 mg daily for days 1-7 of a 28-day cycle (7/28) schedule. AZD6738 is available as 100, 20, and 10 mg tablets. Tablets should be taken daily.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
26
|
16
|
25
|
0
|
|
Overall Study
COMPLETED
|
25
|
15
|
21
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
4
|
0
|
Reasons for withdrawal
| Measure |
Olaparib AZD2881
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
Olaparib & Adavosertib AZD1775
Patients with tumors harboring mutations in HDR genes, including ATM, CHK2, APOBEC, MRE11 complex, will be treated with AZD6738 and olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD6738: Patients will be administered AZD6738 at 160 mg daily for days 1-7 of a 28-day cycle (7/28) schedule. AZD6738 is available as 100, 20, and 10 mg tablets. Tablets should be taken daily.
|
|---|---|---|---|---|
|
Overall Study
Death
|
1
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
0
|
Baseline Characteristics
OLAParib COmbinations
Baseline characteristics by cohort
| Measure |
Olaparib AZD2881
n=26 Participants
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
n=16 Participants
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
n=25 Participants
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
Olaparib & Adavosertib AZD1775
Patients with tumors harboring mutations in HDR genes, including ATM, CHK2, APOBEC, MRE11 complex, will be treated with AZD6738 and olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD6738: Patients will be administered AZD6738 at 160 mg daily for days 1-7 of a 28-day cycle (7/28) schedule. AZD6738 is available as 100, 20, and 10 mg tablets. Tablets should be taken daily.
|
Total
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
47 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
20 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
38 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
29 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
50 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
16 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
49 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=93 Participants
|
16 participants
n=4 Participants
|
25 participants
n=27 Participants
|
—
|
68 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Change from baseline to 16 weeksPopulation: 2 patients not included due to death: 1 from Olaparib AZD2881, 1 from Olaparib \& Capivasertib AZD5363. The Olaparib \& Adavosertib AZD1775 arm was never initiated. One participant in Olaparib \& Ceralasertib AZD6738 arm not included because taken off study by physician decision and 2 subjects withdrew.
Tumor overall response rate (ORR) in molecularly selected patients with measurable disease as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), before versus after 16 weeks of treatment across tumor types in each arm of the study (Note: there will be no formal comparison between arms). 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 at 16 weeks from the start of treatment.
Outcome measures
| Measure |
Olaparib AZD2881
n=25 Participants
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
n=15 Participants
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
n=24 Participants
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
Olaparib & Adavosertib AZD1775
Patients with tumors harboring mutations in HDR genes, including ATM, CHK2, APOBEC, MRE11 complex, will be treated with AZD6738 and olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD6738: Patients will be administered AZD6738 at 160 mg daily for days 1-7 of a 28-day cycle (7/28) schedule. AZD6738 is available as 100, 20, and 10 mg tablets. Tablets should be taken daily.
|
|---|---|---|---|---|
|
Overall Response Rate
CR = complete response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Overall Response Rate
PR = partial response
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Overall Response Rate
SD = stable disease
|
7 Participants
|
5 Participants
|
13 Participants
|
0 Participants
|
|
Overall Response Rate
PD = progressive disease
|
16 Participants
|
9 Participants
|
9 Participants
|
0 Participants
|
Adverse Events
Olaparib AZD2881
Serious events: 10 serious events
Other events: 17 other events
Deaths: 1 deaths
Olaparib & Capivasertib AZD5363
Serious events: 9 serious events
Other events: 3 other events
Deaths: 1 deaths
Olaparib & Ceralasertib AZD6738
Serious events: 17 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Olaparib AZD2881
n=26 participants at risk
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
n=16 participants at risk
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
n=25 participants at risk
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Duodenal obstruction
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Rectal pain
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
General disorders
Non-cardiac chest pain
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Hepatobiliary disorders
Gallbladder pain
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Infections and infestations
Infections and infestations - Other
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Renal and urinary disorders
Urinary retention
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Psychiatric disorders
Confusion
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Psychiatric disorders
Psychosis
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Seizure
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
Other adverse events
| Measure |
Olaparib AZD2881
n=26 participants at risk
Patients with cholangiocarcinoma harboring IDH 1/2 tumors will be treated with olaparib. Patients with tumors harboring mutation in HDR genes will be treated with olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
|
Olaparib & Capivasertib AZD5363
n=16 participants at risk
Patients with tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway will be treated with AZD5363 plus olaparib.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD5363: Patients will be administered AZD5363 at 640 mg twice daily for two days on/five days off (2/7) schedule. Two (2) 200 mg tablets and three (3) 80 mg tablets should be taken twice daily.
|
Olaparib & Ceralasertib AZD6738
n=25 participants at risk
Patients with tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 will be treated with AZD1775 plus olaparib. TP53 mutations must be found on the TP53 mutation eligibility list.
AZD2281: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
AZD1775: The recommended dose will be available no earlier than March 2016.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
34.6%
9/26 • Number of events 21 • Up to 16 weeks
|
12.5%
2/16 • Number of events 3 • Up to 16 weeks
|
44.0%
11/25 • Number of events 25 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other
|
15.4%
4/26 • Number of events 5 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
32.0%
8/25 • Number of events 33 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
23.1%
6/26 • Number of events 9 • Up to 16 weeks
|
12.5%
2/16 • Number of events 4 • Up to 16 weeks
|
32.0%
8/25 • Number of events 8 • Up to 16 weeks
|
|
Gastrointestinal disorders
Vomiting
|
11.5%
3/26 • Number of events 5 • Up to 16 weeks
|
12.5%
2/16 • Number of events 3 • Up to 16 weeks
|
24.0%
6/25 • Number of events 6 • Up to 16 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
18.8%
3/16 • Number of events 4 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Gastrointestinal disorders
Constipation
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
12.0%
3/25 • Number of events 3 • Up to 16 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Investigations
Alanine aminotransferase increased
|
7.7%
2/26 • Number of events 4 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Investigations
Creatinine increased
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
2/26 • Number of events 3 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Investigations
White blood cell decreased
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Investigations
Alkaline phosphatase increased
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Investigations
GGT increased
|
7.7%
2/26 • Number of events 3 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Investigations
Neutrophil count decreased
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Investigations
Investigations - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Investigations
Lymphocyte count increased
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Investigations
Platelet count decreased
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Investigations
Weight loss
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Fatigue
|
11.5%
3/26 • Number of events 5 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
24.0%
6/25 • Number of events 7 • Up to 16 weeks
|
|
Gastrointestinal disorders
Fever
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
General disorders and administration site conditions - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
12.0%
3/25 • Number of events 7 • Up to 16 weeks
|
|
Gastrointestinal disorders
Pain
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Gastrointestinal disorders
Chills
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Edema limbs
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Gastrointestinal disorders
Flu like symptoms
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Malaise
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Gastrointestinal disorders
Non-cardiac chest pain
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.5%
3/26 • Number of events 3 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
12.0%
3/25 • Number of events 6 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/26 • Up to 16 weeks
|
12.5%
2/16 • Number of events 4 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal mucositis
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 3 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 3 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Dizziness
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
12.0%
3/25 • Number of events 5 • Up to 16 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Seizure
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
8.0%
2/25 • Number of events 2 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Infections and infestations
Mucosal infection
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Infections and infestations
Papulopustular rash
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Renal and urinary disorders
Hematuria
|
7.7%
2/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Renal and urinary disorders
Proteinuria
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 2 • Up to 16 weeks
|
|
Renal and urinary disorders
Urine discoloration
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Eye disorders
Blurred vision
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Eye disorders
Retinal vascular disorder
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Immune system disorders
Immune system disorders - Other
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/26 • Up to 16 weeks
|
6.2%
1/16 • Number of events 1 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Cardiac disorders
Chest pain - cardiac
|
3.8%
1/26 • Number of events 1 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
3.8%
1/26 • Number of events 2 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
|
Vascular disorders
Hypotension
|
0.00%
0/26 • Up to 16 weeks
|
0.00%
0/16 • Up to 16 weeks
|
4.0%
1/25 • Number of events 1 • Up to 16 weeks
|
Additional Information
Joseph Paul Eder, MD
Yale School of Medicine: Medical Oncology
Phone: (203) 737-6980
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place