Trial of Olaparib in Combination With AZD5363 (ComPAKT) (ComPAKT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02338622|
Recruitment Status : Completed
First Posted : January 14, 2015
Last Update Posted : February 5, 2020
This is a phase I trial of the combination of the PARP inhibitor olaparib and AKT inhibitor AZD5363.
There are two parts to this study. Part A: dose escalation, and Part B: dose expansion.
Part A will investigate the combination of 300 mg bd of olaparib with intrapatient ascending doses of AZD5363 administered for either 4-days-on, 3-days-off, and 2-days-on, 5-days-off.
Once the Maximum Tolerated Dose (MTD) is reached for both arms (or under the advice from the Safety Review Committee (SRC) one of the schedules will be discontinued), the schedule with the optimum safety and PK/PD profile will be taken forward to a dose expansion phase (Part B).
Part B will evaluate the optimized dose/schedule identified in Part A of the study in patients with (1) BRCA1/2 mutant cancers (with previous disease progression on PARP inhibitor monotherapy), or (2) advanced sporadic tumours (e.g. TNBC, CRPC, HGSOC and tumours with somatic mutations or other aberrations known to result in a hyperactivated PI3K-AKT pathway).
|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancer||Drug: olaparib Drug: AZD5363||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Multi-centre Trial of the Combination of Olaparib (PARP Inhibitor) and AZD5363 (AKT Inhibitor) in Patients With Advanced Solid Tumours|
|Actual Study Start Date :||March 31, 2014|
|Actual Primary Completion Date :||March 21, 2016|
|Actual Study Completion Date :||March 21, 2017|
Experimental: Schedule A: 4 days on, 3 days off
300mg olaparib + intrapatient dose escalation of AZD5363 4 days on, 3 days off
Schema for dose escalation in schedule A (4-days-on, 3-days-off AZD5363)
-1. Olaparib: 200mg, AZD5363 240mg
Other Name: AZD2281
Experimental: Schedule B: 2 days on, 5 days off
300mg olaparib + intrapatient dose escalation of AZD5363 2 days on, 5 days off
Schema for dose escalation in schedule B (2-days-on, 5-days-off AZD5363)
-1. Olaparib: 200mg, AZD5363 400mg
Other Name: AZD2281
- Safety/tolerability of olaparib in combination with AZD5363 [ Time Frame: 3 to 9 weeks at least. ]Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.
- Maximum tolerated dose and recommended Phase II dose of this combination in patients with advanced solid tumours. [ Time Frame: 3 to 9 weeks at least. ]Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.
- Plasma levels of olaparib and AZD5363 using validated assays. [ Time Frame: Average of 2 years ]Plasma levels of olaparib and AZD5363 using validated assays.
- pAkt/Akt, pGSK/GSK3, pS6 kinase/S6 kinase and pPRAS40/PRAS40 ratios in pre- and post-treatment tumour biopsies using validated assays. [ Time Frame: Average of 2 years ]Changes in platelet rich plasma, hair follicles and pre- and post-treatment tumour biopsies using validated assays
- Exploratory biomarkers [ Time Frame: Average of 2 years ]Changes in exploratory biomarkers, including pERK, RAD51, BRCA and PARP expression in pre- and post-treatment tumour biopsies
- Putative predictive biomarkers of response and resistance in archival tumours and fresh tumour biopsies [ Time Frame: Average of 2 years ]Correlate anti-tumour activity of the combination of olaparib and AZD5363 with the detection of putative predictive biomarkers of response and resistance in archival tumours and fresh tumour biopsies
- Disease response by RECIST criteria v1.1 and tumour markers and change in tumour size [ Time Frame: Average of 2 years ]Preliminary assessment of the antitumour putative predictive biomarkers of response and resistance to the combination of olaparib and AZD5363.
- MTD safely established using an intrapatient dose escalation strategy [ Time Frame: Average of 2 years ]Evaluate a novel experimental trial design involving intrapatient dose escalation of AZD5363 in combination with olaparib.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338622
|Northern Institute for Cancer, Freeman Hospital|
|Newcastle, Newcastle Upon Tyne, United Kingdom, NE7 7DN|
|Royal Marsden NHS Foundation Trust|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Principal Investigator:||Timothy A Yap, MBBS MRCP PhD||The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust|