Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Miss Dymphna Lee
ORCID ID
Contact details
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
ORCA@ctc.ucl.ac.uk
Additional identifiers
EudraCT number
2010-023599-24
ClinicalTrials.gov number
Protocol/serial number
11024
Study information
Scientific title
A phase I/II study of Olaparib in addition to cisplatin based concurrent chemoradiotherapy for patients with high risk locally advanced squamous cell carcinoma of the head and neck (HNSCC)
Acronym
ORCA
Study hypothesis
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer in the world, accounting for >7500 of recorded cases in the UK (2006 data). Currently the standard treatment for high risk locally advanced HNSCC is cisplatin chemotherapy alongside high dose radiotherapy, however local recurrence rates are high at approximately 80%. This means there is a real need to look at improving local disease control in this group of patients.
The purpose of this Phase I trial is to assess how olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy (CRT) treatment. This is a dose escalation trial which aims to find out the recommended dose and the best dosing schedule for olaparib in combination with cisplatin based CRT. Patients will be recruited from sites in the UK and the total number recruited will depend on the outcome of the dose escalation (expected to be around 40).
This study is funded by Cancer Research UK and Astra Zeneca.
A placebo controlled, randomised Phase II trial will follow once the recommended dose of olaparib has been established.
Ethics approval
London City and East REC, ref:11/LO/1618 approval pending
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please contact ORCA@ctc.ucl.ac.uk to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Head and Neck Cancer; Disease: Head and Neck
Intervention
The patient numbers in this dose escalation phase I are estimated and will depend on the frequency and severity of adverse events. A modified continual reassessment method (mCRM) design will be used to maximise the information gathered across different cohorts. We aim to minimise patient delay by enrolling patients in parallel into all cohorts within the same dose band.
This is a single arm study.
The trial treatment will involve 2 cycles of induction chemotherapy which will consist of cisplatin and 5-FU (fluorouracil) chemotherapy. This will be followed by olaparib plus cisplatin based chemoradiotherapy for a further 7 weeks.
Induction chemotherapy (6 weeks)
Cisplatin 80mg/m2 i.v. on day 1 and 5-FU 1000mg/m2/day i.v. on day 1-4 (continuous infusion) of a 21 day cycle
Chemoradiotherapy (8 weeks)
Cisplatin will be given at a dose of 35mg/m2 i.v. on day 1 of each week and radiotherapy of 70Gy in 2Gy fractions on day 1-5. Olaparib will be started one week prior to chemoradiotherapy and continued until the end of chemoradiotherapy.
This trial involves a dose escalation of olaparib. The first cohort dose will be 25mg bd (twice daily) for 3 consecutive days, and the maximum dose cohort will be 125mg bd for 5 consecutive days. Patients will be allocated the next available cohort upon entering the study.
Total duration of treatment for this study is 14 weeks, and the follow up is for 2 years post end of treatment.
As of 29/05/2012, the the above study was closed early due to issues surrounding the development and formulation of olaparib. No patients were recruited.
Intervention type
Drug
Phase
Phase I/II
Drug names
Olaparib
Primary outcome measures
To assess the frequency of Dose Limiting Toxicities (DLTs) and adverse events.
Secondary outcome measures
1. Other efficacy endpoints: complete response rate (cRR)
2. Time to loco-regional and any progression
Overall trial start date
01/12/2011
Overall trial end date
01/12/2015
Reason abandoned
Lack of staff/facilities/resources
Eligibility
Participant inclusion criteria
1. Histologically confirmed high risk locally advanced HNSCC (TNM staging T(any) N2 or N3 M0, bulky T3 or T4 N(any) M0) who would normally be offered cisplatin-based radical chemoradiotherapy
2. Estimated life expectancy of at least 12 weeks
3. WHO performance status of 0 or 1
4. Aged more than or equal to 18 years
5. Adequate organ function:
5.1. Absolute neutrophils =1.5 x 10*9/L
5.2. Platelets =100 x 10*9/L
5.3. Haemoglobin =10g/dl (to be maintained above 12g/dl whilst on CRT treatment)
5.4. Creatinine =1.5 x ULN
5.5. Glomerular filtration rate (GFR) =60 ml/min
5.6. Serum bilirubin = 1.25 x ULN
5.7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 x ULN
6. Patients willing to use contraception for the duration of the trial and for six months post treatment
7. Able to give informed consent
8. Patient is willing and able to comply with the protocol for the duration of the study, including the treatment plan investigations required and follow up visits; Target Gender: Male & Female ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 60; UK Sample Size: 60;
Participant exclusion criteria
1. Head & neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, oral cavity tumours (tumours of the oral cavity)
2. Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
3. Confirmed distant metastatic disease
4. Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
5. Previous therapy with a PARP inhibitor
6. Previous chemotherapy, immunotherapy or radiotherapy within the last 28 days prior to registration
7. Prior history of malignancy, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate, and unless the patient has been free of malignancy for a period of 3 years prior to first dose of trial drug
8. Women who are pregnant or lactating
9. Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of trial drugs
10. Peripheral neuropathy > Grade 2 (lower grade neuropathy considered significant by treating clinician may be considered an exclusion criterion)
11. Significant hearing difficulties (patients with mildly impaired hearing must be made aware of potential ototoxicity)
12. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinicians judgement, could interfere with patient safety or obtaining informed consent
13. Known hepatitis B or C infection
14. Immunocompromised patients [e.g. Known human imunodeficiency virus (HIV) positive status]
15. Active uncontrolled infection
16. The current use of drugs which are known to inhibit Cytochrome P450 3A4 (CYP3A4) which cannot be discontinued for the duration of trial treatment
Recruitment start date
01/12/2011
Recruitment end date
01/12/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK & UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom
Funders
Funder type
Industry
Funder name
AstraZeneca (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Funder name
Cancer Research UK (CRUK) (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary