Condition category
Cancer
Date applied
20/04/2015
Date assigned
20/04/2015
Last edited
26/08/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Dr Liz-Anne Lewsley

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
The Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G120YN
United Kingdom
01413017193
liz-anne.lewsley@glasgow.ac.uk

Additional identifiers

EudraCT number

2014-002074-37

ClinicalTrials.gov number

Protocol/serial number

PIONEER-2014

Study information

Scientific title

A Phase I study of olaparib in combination with chemoradiation in locally advanced pancreatic cancer

Acronym

PIONEER

Study hypothesis

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

Scotland A Research Ethics Committee, 03/03/2015, ref: 15/SS/0011

Study design

Interventional

Primary study design

Interventional

Secondary study design

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format

Condition

Locally advanced pancreatic cancer

Intervention

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

Phase

Phase I

Drug names

Olaparib

Primary outcome measures

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 trial start date

01/05/2015

Overall trial end date

30/04/2019

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

18-42

Participant 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

Recruitment start date

01/05/2015

Recruitment end date

01/05/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Beatson West of Scotland Cancer Centre
Glasgow
G120YN
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
Le15WW
United Kingdom

Trial participating centre

Belfast City Hospital
Belfast
BT97AB
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Trust
London
SE19RT
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G120XH
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Organisation

The Unversity of Glasgow

Sponsor details

University Avenue
GLASGOW
G128QQ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

AstraZeneca

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes