Trial of Olaparib in Combination With AZD5363 (ComPAKT) (ComPAKT)
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|ClinicalTrials.gov Identifier: NCT02338622|
Recruitment Status : Unknown
Verified January 2015 by Royal Marsden NHS Foundation Trust.
Recruitment status was: Recruiting
First Posted : January 14, 2015
Last Update Posted : January 19, 2015
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|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||58 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|
|Study Start Date :||March 2014|
|Estimated Primary Completion Date :||October 2015|
|Estimated Study Completion Date :||October 2015|
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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338622
|Contact: Alison Turner, PhD||+44 (0)20 8661 firstname.lastname@example.org|
|Contact: Nitharsan Sathiyayogan, MSc||+44 (0)20 8722 email@example.com|
|Northern Institute for Cancer, Freeman Hospital||Recruiting|
|Newcastle, Newcastle upon Tyne, United Kingdom, NE7 7DN|
|Contact: Elizabeth R Plummer, MD +44(0)191 213844 firstname.lastname@example.org|
|Principal Investigator: Elizabeth R Plummer, MD|
|Royal Marsden NHS Foundation Trust||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Contact: Timothy A Yap, PhD 0208 661 3539 email@example.com|
|Principal Investigator: Timothy A Yap, PhD|
|Principal Investigator:||Timothy A Yap, MBBS MRCP PhD||The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust|