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Trial registered on ANZCTR


Registration number
ACTRN12616000931471
Ethics application status
Approved
Date submitted
23/05/2016
Date registered
13/07/2016
Date last updated
17/02/2020
Date data sharing statement initially provided
11/02/2019
Date results information initially provided
11/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Cancer Molecular Screening and Therapeutics (MoST) Program Substudy addendum 1: Palbociclib
Scientific title
MoST Substudy 1: Single arm, open label, signal seeking, phase Ib/IIa trial of the CDK4/6 inhibitor palbociclib in patients with tumours with amplified D-type cyclins or CDK4 or inactivation of CDKN2A.
Secondary ID [1] 289276 0
CTC0141
Universal Trial Number (UTN)
U1111-1182-6652
Trial acronym
Linked study record
ACTRN12616000908437

Health condition
Health condition(s) or problem(s) studied:
Cancer 298862 0
Condition category
Condition code
Cancer 298929 298929 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Palbociclib will be administered orally once daily at a dose of 125mg/day (one capsule) for days 1-21, every 28 day cycle (3 weeks on, 1 week off).

Palbociclib will be administered continuously until documented disease progression, intolerable toxicity or withdrawal for another reason.

The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each patient and subsequent returns.
Intervention code [1] 294824 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298397 0
The primary end point is disease control defined as a composite of: 1. Objective tumour response (OTR), based on complete and partial responses using cancer specific response criteria; and/or 2. Time to progressive disease exceeds the documented time to progressive disease on the last treatment prior to substudy entry by at least 1.3 times (TTP2/TTP1 > 1.3). * Or exceeds 6 months if TTP1 is not evaluable.
Timepoint [1] 298397 0
CT scans for disease evaluation will take place every 8 weeks until progression.

Where disease evaluation is not based on CT scans alternative validated guidelines, such as Gynecologic Cancer Intergroup (GCIG) and Prostate Cancer Working Group 2 (PCWG2) criteria will be employed.

Where radiological progression cannot be assessed, evidence for clinical progression will be documented. These data will be collected from patient questionnaires or clinical reports to supplement the primary outcome. Health related quality of life during treatment will be assessed using the EORTC QLQ-C30 tool or the Brief Pain Inventory for patients with symptomatic disease as appropriate.

Questionnaires will be administered at baseline and then every 4 weeks until progression.

Duration of the study is estimated at 2 years
Secondary outcome [1] 324021 0
Overall survival (OS) (death from any cause)
Timepoint [1] 324021 0
For the duration of the study estimated at 2 years
Secondary outcome [2] 324022 0
Safety and tolerability of treatment (rates of adverse events) assessed according to CTC AE version 4.03.

Some, but not all, common expected adverse events include: tiredness, low white blood cells, nausea and/or vomiting, anaemia, diarrhoea or constipation. The patient information sheet will contain this information.
Timepoint [2] 324022 0
Until 30 days after the last treatment
Secondary outcome [3] 324023 0
Health related quality of life during treatment will be assessed using the EORTC QLQ-C30 tool. or using the Brief Pain Inventory for patients with symptomatic disease as appropriate
Timepoint [3] 324023 0
For the duration of the study at baseline (before treatment) and then every 4 weeks until progression.

Eligibility
Key inclusion criteria
To be eligible for treatment in a substudy, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified for entry into molecular screening at the time of registration to a treatment substudy. In addition, they must meet all the inclusion criteria and none of the exclusion criteria in the substudy addendum at the time of registration.

1. Confirmation of molecular eligibility by the molecular tumour board;
2. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
3. Clinical or radiological progression on or following last anticancer therapy;
4. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
5. Meet any additional inclusion criteria specified in the relevant substudy addendum;
6. Signed, written informed consent to participation in the specific treatment substudy.

Inclusion Criteria specific to this sub-study :
1. Subjects with tumours carrying somatic mutations in the Rb-pathway including amplification or activating mutations in CCND1, CCND2, CCND3 or CDK4, or loss of function mutations in CDKN2A;
2. Able to swallow capsules.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will include those relevant for screening but also include:
1. Contraindications to investigational product, as listed in the substudy addendum and outlined in the Investigator Brochure appended to each substudy module;
2. Known history of hypersensitivity to active or inactive components of investigational product;
3. Previous treatment with the same agent or same class of agent;
4. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
o Radiation therapy, surgery or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
o Immunotherapy within 28 days prior to the first dose of study treatment;
o Chemotherapy, biologic therapy, investigation therapy or hormonal therapy within 30 days or 5 half-lives of a drug (whichever is longer), prior to the first dose of study treatment;
5. Administration of any non-oncologic investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment;
6. Any additional exclusion criteria specified in the relevant substudy addendum.

Exclusion Criteria specific to this sub-study:
1. Subjects with breast cancer, mantle cell lymphoma, myeloma, or germ cell tumours;
2. Patients with steroid-responsive tumours must be on a stable dose of dexamethasone for a minimum of 14 days prior to registration
3. Contraindications to palbociclib, including known hypersensitivity to any of the components of palbociclib;
4. Prior treatment with a CDK inhibitor.

Study design
Purpose of the study
Treatment
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5836 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 5837 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [3] 10248 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 13281 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 13282 0
2050 - Camperdown
Recruitment postcode(s) [3] 21913 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 293657 0
Government body
Name [1] 293657 0
Office for Health and Medical Research
Address [1] 293657 0
Locked Mail Bag 961
North Sydney NSW 2059
Country [1] 293657 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trial Centre
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 292492 0
None
Name [1] 292492 0
Address [1] 292492 0
Country [1] 292492 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295093 0
St Vincent's Hospital Ethics Committee
Ethics committee address [1] 295093 0
St Vincent’s Hospital Research Office
Translational Research Centre
97-105 Boundary Street
Darlinghurst NSW 2010
Ethics committee country [1] 295093 0
Australia
Date submitted for ethics approval [1] 295093 0
01/02/2016
Approval date [1] 295093 0
01/04/2016
Ethics approval number [1] 295093 0
HREC/16/SVH/23

Summary
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of palbociclib in patients with advanced cancers and tumours with mutations in components of the Rb-pathway.
Who is it for? All participants in this study must have completed screening as part of the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437), and been identified as having tumours carrying somatic mutations in the Rb-pathway including amplification or activating mutations in CCND1, CCND2, CCND3 or CDK4, or loss of function mutations in CDKN2A. They must also be able to swallow capsules.
Study details All participants in this study will take the drug, palbociclib, orally once daily at a dose of 125mg/day for days 1-21, every 28 day cycle (3 weeks on, 1 week off). Treatment will continue until progression, unacceptable toxicity or withdrawal. All participants will undergo assessments at 8 weekly intervals or as clinically indicated in order to evaluate tumour response, safety and tolerability of treatment, health related quality of life during treatment, and overall survival.

We cannot guarantee that patients will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that palbociclib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66098 0
Prof David Thomas
Address 66098 0
Garvan Institute of Medical Research
The Kinghorn Cancer Centre, 370 Victoria Street
Darlinghurst NSW 2010
Country 66098 0
Australia
Phone 66098 0
+61293555770
Fax 66098 0
+612 9355 5872
Email 66098 0
d.thomas@garvan.org.au
Contact person for public queries
Name 66099 0
Dr Lucille Sebastian
Address 66099 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119–143 Missenden Road, Camperdown NSW 2050
Country 66099 0
Australia
Phone 66099 0
+61295625000
Fax 66099 0
Email 66099 0
most@ctc.usyd.edu.au
Contact person for scientific queries
Name 66100 0
Prof David Thomas
Address 66100 0
Garvan Institute of Medical Research
The Kinghorn Cancer Centre, 370 Victoria Street
Darlinghurst NSW 2010
Country 66100 0
Australia
Phone 66100 0
+61293555770
Fax 66100 0
+612 9355 5872
Email 66100 0
d.thomas@garvan.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No patient permission to share data outside this study.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary