Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000048785
Ethics application status
Approved
Date submitted
13/12/2012
Date registered
15/01/2013
Date last updated
15/01/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
AKTRES study: A Biologic Study of the early effects and determinants of AKT inhibition using GSK2110183 alongside chemotherapy in patients with Platinum RESistant Adenocarcinoma of the ovary
Scientific title
AKTRES study: A Biologic Study of the early effects and determinants of AKT inhibition using GSK2110183 alongside chemotherapy in patients with Platinum RESistant Adenocarcinoma of the ovary
Secondary ID [1] 281677 0
Nil
Universal Trial Number (UTN)
Trial acronym
AKTRES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Platinum Resistant Adenocarcinoma of the ovary 287961 0
Condition category
Condition code
Cancer 288348 288348 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
As part of the main study, patients will initially undergo certain tests and scans to make sure that the study is right for them. During this time, three extra 10ml tubes of blood (30ml, 6-8 teaspoons) will be taken for this sub-study. During routine blood tests before each cycle of chemotherapy and maintenance phase of the GSK2110183 drug (see main study details below), an extra 30mls of blood will be collected. At the end of the study, a final 30mls of blood will also be collected.

Patients will also be asked to have a biopsy of their tumour before starting treatment (chemotherapy) and during treatment. The biopsies will give the researchers information about how the drug works and help to develop tests that predict who might respond to treatment. The tests involve looking at the molecules in the tumour tissue. Biopsies will be done only if it is easy to perform with minimal discomfort to participants. This will be done as a day case at the hospital after using a local numbing medicine to allow painless biopsy from the area by an experienced radiologist. The second biopsy is optional.

Addditionally, at any point during the study, should a participant require a clinical procedure to remove fluid from their abdomen, researchers would like to store some of the fluid which would otherwise be disposed of.

To see details of the main study please go to; http://www.clinicaltrials.gov/ct2/show/NCT01653912?term=NCT01653912&rank=1
Intervention code [1] 286210 0
Other interventions
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288511 0
To correlate pharmacodynamic evidence of AKT pathway inhibition with therapeutic outcome in patients with platinum resistant ovarian cancer receiving GSK2110183 plus combination chemotherapy.
Timepoint [1] 288511 0
ELISA-detected decrease in phosphorylated PRAS40 (as ratio of total PRAS40) and increase in pAKT S473 (as a ratio of total AKT) in available tumour samples before and after 1 cycle of treatment with GSK2110183 plus chemotherapy compared to best response to study treatment (RECIST 1.1), Overall Response, CA125 response and PFS
Secondary outcome [1] 300362 0
To compare changes to the proteomic and immunohistochemical profile of the extended AKT pathway with response and PFS using tumour tissue taken before and following one cycle of trial therapy with GSK2110183 plus combination chemotherapy.
Timepoint [1] 300362 0
1) Compare changes in AKT, pAKT, PRAS40, pPRAS40, Ki67, LARP1 by IHC in tumour tissue before and after 1 cycle of treatment with GSK2110183 plus chemotherapy.
2) Compare changes in expression of other components of the extended AKT pathway by reverse phase protein array (RPPA) in tumour tissue before and after 1 cycle of treatment with GSK2110183 plus chemotherapy.
3) To correlate, where possible, with markers identified by IHC from archival tumour samples.
Secondary outcome [2] 300363 0
To correlate tumour mutational profiles with patient outcome in terms of clinical response
Timepoint [2] 300363 0
To determine pre- treatment biopsy tumour mutation profiles of known cancer genes by Sequenom OncoMap assays and correlate with patient outcome in terms of best RECIST (1.1) response, Overall Response, CA125 response and PFS. To correlate, where possible, with mutations identified in archival tumour samples
Secondary outcome [3] 300364 0
To correlate change in blood derived markers before and after treatment with pharmacodynamic measures (described above) and with patient outcome
Timepoint [3] 300364 0
To correlate levels of blood derived markers (such as circulating tumour cells, PBMCs for germline DNA and RPPA analysis and plasma LARP1 by ELISA) obtained during treatment to those at baseline with protein or genomic changes identified above and also with patient outcome (RECIST 1.1) in terms of best RECIST (1.1) response, Overall Response, CA125 response and PFS.

Eligibility
Key inclusion criteria
All patients considered eligible to enter study PKB116611 but fulfilling the additional eligibility criteria listed below will be prospectively offered participation in this study

Female at least 18 years of age at the time of signing the informed consent form and capable of giving written informed consent, which includes willingness to comply with the requirements and restrictions listed in the consent form

Tumour tissue measuring >2cm long axis amenable to direct biopsy or biopsy via image-guidance

Platinum-resistant ovarian cancer as defined as radiological evidence of disease progression within 6 months of completion of platinum-containing chemotherapy
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Concurrent medication with warfarin or low molecular weight heparin (heparin use is acceptable if it has been discontinued for 2 days preceding biopsy)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/07/2012
Actual
23/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 313 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [2] 314 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 6115 0
3052 - Parkville
Recruitment postcode(s) [2] 6116 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 4751 0
United Kingdom
State/province [1] 4751 0
London

Funding & Sponsors
Funding source category [1] 286464 0
Self funded/Unfunded
Name [1] 286464 0
Country [1] 286464 0
Primary sponsor type
Hospital
Name
Royal Women's Hospital
Address
20 Flemington Road
Parkville, VIC, 3052
Country
Australia
Secondary sponsor category [1] 285252 0
Hospital
Name [1] 285252 0
Peter MacCallum Cancer Centre
Address [1] 285252 0
Level 5 DCM
Peter MacCallum Cancer Centre
East Melbourne, Vic, 3002
Country [1] 285252 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288540 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 288540 0
St Andrews Place
East Melbourne, Victoria, 3002
Ethics committee country [1] 288540 0
Australia
Date submitted for ethics approval [1] 288540 0
Approval date [1] 288540 0
11/09/2012
Ethics approval number [1] 288540 0
HREC/12/PMCC/19

Summary
Brief summary
This is a biological study, which aims to answer novel questions about the molecular status of cells from patients with platinum-resistant ovarian cancer before and after treatment with the AKT inhibitor GSK2110183 given in combination with chemotherapy (in the accompanying PKB116611 study). We will biopsy tumour tissue and collect blood samples from PKB116611 participants with platinum resistant ovarian cancer prior to and following treatment in order to perform the following studies on tissue samples:

1) Immunohistochemical, ELISA and protein array (RPPA) based analysis of tumour biopsies for markers such as AKT, pAKT, PRAS40, pPRAS40, Ki67, LARP1 and multiple components of the extended AKT pathway
2) Genomic analysis of archived tumour samples for mutations in known cancer genes by Sequenom OncoMap assays.
3) Analysis of blood-derived markers in circulating tumour cells (CTCs), peripheral blood mononuclear cells (PBMCs) and plasma.
4) Analysis (where appropriate) of ascites (or pleural effusion) for markers such as AKT, pAKT, PRAS40, pPRAS40, Ki67 and LARP1.
Trial website
http://www.clinicaltrials.gov/ct2/show/NCT01653912?term=NCT01653912&rank=1
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36618 0
Ms Anne Hamilton
Address 36618 0
20 Flemington Road,
Parkville, VIC, 3052
Country 36618 0
Australia
Phone 36618 0
+61396561804
Fax 36618 0
Email 36618 0
[email protected]
Contact person for public queries
Name 36619 0
Sara Scalzo
Address 36619 0
20 Flemington Road,
Parkville, VIC, 3052
Country 36619 0
Australia
Phone 36619 0
+61383453546
Fax 36619 0
Email 36619 0
[email protected]
Contact person for scientific queries
Name 36620 0
Anne Hamilton
Address 36620 0
20 Flemington Road,
Parkville, VIC, 3052
Country 36620 0
Australia
Phone 36620 0
+61396561804
Fax 36620 0
Email 36620 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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