Condition category
Cancer
Date applied
02/05/2014
Date assigned
02/06/2014
Last edited
29/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Anthony Chalmers

ORCID ID

http://orcid.org/0000-0002-1746-7278

Contact details

The Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
+44 (0)141 301 7092
anthony.chalmers@glasgow.ac.uk

Additional identifiers

EudraCT number

2014-001216-19

ClinicalTrials.gov number

Protocol/serial number

GN13ON355

Study information

Scientific title

Short-course radiotherapy plus olaparib for newly diagnosed glioblastoma in patients unsuitable for radical chemoradiation: a randomised phase II clinical trial preceded by a lead-in phase I dose escalation study

Acronym

PARADIGM

Study hypothesis

The objective of phase I is to establish the maximum tolerated dose of olaparib when given in combination with radiotherapy.
The objectives of phase II are to obtain evidence that adding olaparib to radiotherapy improves overall survival in this patient population, and to justify a subsequent phase III trial.
Additional objectives are to document the safety, toxicity and quality of life associated with this combination.

Ethics approval

West of Scotland Research Ethics Service, 13/11/2014, ref: 14/WS/1096

Study design

Phase I dose-escalation study followed by a Phase II randomised double-blind study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Gliomas

Intervention

All patients will receive hypofractionated, short-course radiotherapy (40 Gray in 15 fractions) over 19 ¨C 21 days. In the Phase I component, escalating doses of oral olaparib will be delivered daily throughout the radiotherapy treatment period. Olaparib will be commenced 3 days prior to radiation and will continue throughout treatment for a total of 22 - 24 days.

In Phase II, patients will be randomised to receive radiotherapy plus placebo PO (control arm) or radiotherapy plus olaparib PO at the maximum tolerated dose (MTD) established in Phase I (or a maximum dose of 200 mg PO twice daily if MTD not reached). Olaparib or placebo will be commenced 3 days prior to radiation and will continue throughout treatment for a total of 22 - 24 days.

Intervention type

Drug

Phase

Phase I/II

Drug names

Olaparib

Primary outcome measures

Phase I: The recommended dose of olaparib when administered in combination with radiotherapy
Phase II: Overall survival

Secondary outcome measures

Phase I: The DLT (Dose-Limiting Toxicity) and the safety and tolerability of olaparib administered in combination with radiotherapy.
Phase II:
1. Progression-free survival measured by MRI scans during follow-up and will be assessed in accordance with the RANO guidelines
2. Toxicity measured using the CTCAE v.4.0 criteria and recorded at each follow-up visit
3. Quality of life which will be measured by the completion of QLQ30, BN20 and EQ-5D questionnaires completed by the participant at baseline and each follow-up visit

Overall trial start date

01/11/2014

Overall trial end date

31/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 18 - 69: WHO performance status 2 at initial oncology consultation or performance status 0-1 but otherwise unsuitable for radical radiotherapy with concomitant and adjuvant temozolomide.
2. Age over 70: WHO performance status 0 or 1 at initial oncology consultation
3. Histologically confirmed diagnosis of glioblastoma
4. Life expectancy greater than 12 weeks
5. No previous radiotherapy or chemotherapy for primary or secondary CNS malignancy
6. Adequate haematological, hepatic and renal function defined as below:
Haemoglobin >/= 9.0 g/dL, absolute neutrophil count >/= 1.5 x 109/L, platelet count >/= 100 x 109/L, bilirubin </= 1.5 x upper limit of normal (ULN), Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) </= 2.5 x ULN, Adequate renal function with creatinine clearance / glomerular filtration rate > 50 ml/min. If the creatinine clearance / glomerular filtration rate is less than 50 ml/min as calculated by the Cockroft-Gault/Wright formula, then the creatinine clearance / glomerular filtration rate should be measured by either a radio-isotope technique or by 24-hour urine collection.
7. Ability to provide written informed consent prior to participating in the trial and any trial related procedures being performed
8. Willingness to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures
9. Ability to swallow oral tablets/capsules

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

Phase I 12-24 patients. Phase II - 140 patients.

Participant exclusion criteria

1. WHO performance status >2
2. Life expectancy less than 12 weeks
3. Active concurrent malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix). If history of prior malignancy, must be disease-free for >5 years.
4. Prior treatment for primary or secondary CNS malignancy
5. Confusion or altered mental state that would prohibit understanding and giving of informed consent
6. Concomitant treatment with medicines detailed in section 5.10 of protocol.
7. Female patients who are able to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) effective at the first administration of either IMP, throughout the trial, and for six months afterwards, are considered eligible.
8. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] effective at the first administration of IMP, throughout the trial, and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
9. Administration of any investigational drug within 28 days of receiving the first dose of trial treatment.

Recruitment start date

03/03/2015

Recruitment end date

30/11/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde (UK)

Sponsor details

C/O Dr Nathaniel Brittain
Academic Research Co-ordinator
Greater Glasgow Health Board
Research and Development Central Office
The Tennent Institute
1st Floor
Western Infirmary General
38 Church Street
Glasgow
G11 6NT
United Kingdom
+44 (0)141 211 8544
nathaniel.brittain@ggc.scot.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.nhsggc.org.uk/r&d

Funders

Funder type

Industry

Funder name

Astra Zeneca (UK) - endorsed by Cancer Research UK

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in high impact medical journals and presentation at national meetings.

Intention to publish date

31/03/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

29/03/2016: Availability of participant level data added. 24/03/2016: Ethics approval information added.