A study for patients with advanced pancreatic cancer looking at adding olaparib to chemotherapy with radiotherapy (chemoradiation)

ISRCTN	ISRCTN10361292
DOI	https://doi.org/10.1186/ISRCTN10361292
EudraCT/CTIS number	2014-002074-37
IRAS number	159690
Secondary identifying numbers	PIONEER-2014, IRAS 159690

Submission date: 20/04/2015
Registration date: 20/04/2015
Last edited: 22/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-olaparib-with-chemoradiation-for-pancreatic-cancer-pioneer

Contact information

Dr Liz-Anne Lewsley
Public

Cancer Research UK Clinical Trials Unit
The Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G120YN
United Kingdom

Phone	01413017193
Email	liz-anne.lewsley@glasgow.ac.uk

Study information

Study design	Interventional
Primary study design	Interventional
Secondary study design
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format
Scientific title	A Phase I study of olaparib in combination with chemoradiation in locally advanced pancreatic cancer
Study acronym	PIONEER
Study objectives	The hypothesis to be tested is that olaparib can be safely combined with a standard chemoradiation regimen in locally advanced, non-metastatic pancreatic cancer and that the addition of a PARP inhibitor to the standard fluoropyrimidine - based chemo-radiation backbone might potentiate the effects of this combined modality therapy in patients with both locally advanced, inoperable pancreatic cancer as well in those with borderline resectable disease.
Ethics approval(s)	Approved 03/03/2015, Scotland A Research Ethics Committee (2nd Floor Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, United Kingdom; +44 (0)1314655680; Manx.Neill@nhslothian.scot.nhs.uk), ref: 15-SS-0011
Health condition(s) or problem(s) studied	Locally advanced pancreatic cancer
Intervention	Current interventions as of 08/04/2020: Patients will be treated as follows: 1. Olaparib (starting day three days prior to chemo-radiation in escalating doses* orally twice daily (Mon-Fri) until final day of radiation therapy 2. Capecitabine 830mg/m2 PO twice daily Mon-Fri until the final date of radiation therapy. 3. Radiotherapy (50.4 Gy in 28 fractions) Mon-Fri Expansion cohort of up to 12 patients (minimum of 6) with borderline resectable disease will be treated at the Olaparib MTD. The MTD of Olaparib in the dose escalation phase is 100mg bd _____ Previous interventions: Patients will be treated as follows: 1. Olaparib (starting day three days prior to chemo-radiation in escalating doses orally twice daily (Mon-Fri) until final day of radiation therapy 2. Capecitabine 830mg/m2 PO twice daily Mon-Fri until the final date of radiation therapy. 3. Radiotherapy (50.4 Gy in 28 fractions) Mon-Fri *Expansion cohort of 12 patients with borderline resectable disease will be treated at the Olaparib MTD
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	Olaparib
Primary outcome measure	The primary objective is to determine the Maximum Tolerated Dose (MTD) of olaparib when administered in combination with standard capecitabine-based chemo-radiation in patients with pancreatic cancer. Toxicity will be assessed on an ongoing basis throughout the treatment phase of the study.
Secondary outcome measures	1. To identify the DLT (Dose-Limiting Toxicity) of olaparib when administered in combination with standard capecitabine-based chemo-radiation in these patients. DLTs will be assessed weekly for six weeks during patient treatment in the dose escalation phase. 2. To explore the safety and tolerability of olaparib when administered in combination with standard capecitabine-based chemo-radiation including in a cohort of patients with “borderline” resectable pancreatic ductal adenocarcinoma. This will be assessed on an ongoing basis during the six week treatment period of the patients in the dose expansion phase.
Overall study start date	01/05/2015
Completion date	31/03/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	18-42
Key inclusion criteria	1. Histologically or cytologically confirmed locally advanced inoperable pancreatic ductal adenocarcinoma 2. Patients with clearly un-resectable disease on anatomical criteria as determined by a multi-disciplinary team and considered to be candidates for combined modality treatment with chemo-radiation 3. Patients must have had a partial response or stable disease following 3 cycles of induction chemotherapy with gemcitabine and capecitabine as described in Appendix 1, and have a tumour diameter of 6cm or less 4. Performance status ≤ 1 (ECOG, Appendix 3) 5. Age ≥ 16 years 6. Evaluable or measurable disease 7. Estimated life expectancy greater than 3 months 8. Adequate haematological function as defined by: 8.1. Haemoglobin (Hb) > 10g/dl (no blood transfusions in the 28 days prior to trial entry) 8.2. Neutrophil Count > 1.5 x 109/l (no features suggestive of MDS/AML on peripheral blood smear) 8.3. White Blood Cells (WBC) >3x109/L 8.4. Platelets > 100 x 109/l 8.5. Bilirubin < 1.5 x upper limit of normal (ULN) 8.6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN 8.7. 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 Cockcroft-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 9. Able to swallow oral tablets/capsules 10. Able to comply with study procedures 11. Written informed consent 12. Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of trial treatment 13. Postmenopausal as defined as: 13.1. Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, 13.2. LH and FSH levels in the post-menopausal range for women under 50, 13.3. Surgical sterilisation (bilateral oophorectomy or hysterectomy). Dose Expansion Cohort Additional Eligibility Criteria 1. Patients with pancreatic ductal adenocarcinoma who are considered by a multi-disciplinary team to have “borderline” resectable disease based on their anatomical findings during pre-operative staging
Key exclusion criteria	1. Any prior anti-cancer therapy for pancreatic cancer including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents (except induction chemotherapy) 2. Patients with known metastatic disease 3. Pregnant or lactating women 4. Women of childbearing age and potential who are not willing to use an two highly effective methods of contraception as detailed in section 11.3. Male patients of childbearing potential will also be excluded if either they or their female partner are not willing to use two highly effective methods of contraception as detailed in section 11.3. In addition, both of the above will be excluded if they are not willing to use contraception for 12 months after the last dose. Men with pregnant or lactating partners should be advised to user barrier contraception to prevent exposure to the foetus or neonate. 5. Patients who are known to be HIV positive, or who are known to have positive Hepatitis B or C serology 6. Any evidence of uncontrolled cardiac disease or any other serious medical or psychiatric disorder that would be, in the opinion of the investigator, a contra-indication to either the trial procedures or to therapy with olaparib or capecitabine 7. Patients with second or third degree heart block, family history of QT prolongation or shortening, history of arrhythmia, or familial sudden death or QT interval at screening of >450 ms (male) / >470 ms (female) 8. Patients receiving concomitant medications known to cause QT prolongation 9. Patients with known DPD deficiency 10. Patients with a lack of physical integrity of the GI tract leading to a malabsorption syndrome or intestinal obstruction that would impair the administration and absorption of oral therapy 11. Participation in another clinical trial with an investigational product during the last 12 months 12. Any previous treatment with a PARP inhibitor, including olaparib. 13. Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. In addition , to avoid potential reductions in exposure due to drug interactions and, therefore, a potential reduction in efficacy, the following CYP3A4 inducers are excluded: Phenytoin, fiampicin, rifapentin, rifabutin, carbamazepine, phenobarbitone, nevirapine, modafinil and St John’s Wort (Hypericum perforatum; wash-out period for phenobarbitone 5 weeks and for any of the others 3 weeks) 14. Blood transfusions within 1 month prior to trial start 15. Patients with myelodysplastic syndrome/acute myeloid leukaemia 16. Major surgery within 14 days of starting trial treatment and patients must have recovered from any effects of major surgery 17. Patients with a known hypersensitivity to olaparib or any of the excipients of the product 18. Patients with uncontrolled seizures 19. Patients with grade III / IV non-haematological toxicity related to capecitabine during induction chemotherapy except for alopecia or nausea and vomiting unless not controlled with maximal anti-emetics support 20. Patients unable to tolerate standard dose of capecitabine during induction chemotherapy
Date of first enrolment	01/05/2015
Date of final enrolment	31/07/2021

Locations

Countries of recruitment

Northern Ireland
Scotland
United Kingdom

Study participating centres

The Beatson West of Scotland Cancer Centre

1053 Great Western Road
Glasgow
G120YN
United Kingdom

Belfast City Hospital

Lisburn Road
Belfast
BT97AB
United Kingdom

Sponsor information

NHS Greater Glasgow and Clyde
Hospital/treatment centre

J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
Scotland
United Kingdom

Website	http://www.nhsggc.org.uk/
"ROR"	https://ror.org/05kdz4d87

The Unversity of Glasgow
University/education

University Avenue
Glasgow
G128QQ
Scotland
United Kingdom

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

AstraZeneca
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

22/09/2023: The study contact clarified that the study recruitment was paused between 16/03/2020 and 19/06/2020.
20/09/2023: The following changes were made:
1. IRAS number added.
2. The overall study end date was changed from 31/07/2022 to 31/03/2022.
3. The suspension of recruitment was removed.
01/05/2020: Due to current public health guidance, recruitment for this study has been paused.
08/04/2020: The following changes were made to the trial record:
1. The interventions were changed.
2. The overall end date was changed from 30/04/2019 to 31/07/2022.
3. The recruitment end date was changed from 01/05/2017 to 31/07/2021.
4. The trial participating centres "Guy's and St Thomas' NHS Trust and Leicester Royal Infirmary" were removed.