Head and Neck CancerPhase 1ORCA-2NCT02308072
Phase I Study of Olaparib Combined With Cisplatin-based Chemoradiotherapy to Treat Locally Advanced Head and Neck Cancer
A Phase 1 study testing Olaparib, Cisplatin and IMRT in people with Head and Neck Cancer, run by University College, London at 3 sites in United Kingdom.
Trial summary
The phase I trial aims to determine the recommended phase II dose (RP2D) and schedule of olaparib in combination with standard cisplatin-based chemoradiotherapy, in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (HNSCC), by assessing the safety and tolerability of the treatment… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Olaparib, Cisplatin and IMRT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Sep 2015to 24 Apr 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed high-risk locally advanced HNSCC, patients who would normally be offered cisplatin-based radical chemoradiotherapy
- Estimated life expectancy of at least 16 weeks
- WHO performance status 0 or 1
- Aged ≥18 years
- Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0 or 1, haemoglobin grade 0 or 1
- Adequate renal function: Creatinine grade 0 or 1, Calculated GFR ≥60 mL/min (if calculated value is <60 mL/min then an isotope GFR assessment should be performed or an estimation from 24h urine collection)
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- Adequate liver function: Serum bilirubin grade 0 or 1, AST or ALT grade 0 or 1
- Patients must be able to swallow olaparib tablets
- Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
- Able to give informed consent
- Patients willing and able to comply with the protocol for the duration of the study
Who cannot join
- Head \& neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, Oral squamous cell carcinomas (tumours of the oral cavity), Low risk Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
- Confirmed distant metastatic disease
- Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
- Previous therapy with a PARP inhibitor
- Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
- Prior history of malignancy, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate. Patient must have been free of malignancy for a period of 3 years prior to first dose of trial drug
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- Women who are pregnant or lactating
- Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
- Grade 3 or 4 peripheral neuropathy - If considered significant by the treating clinician a lower grade neuropathy may be considered as exclusion criterion
- Significant hearing difficulties or tinnitus (deaf patients can be included) - Whilst not excluded, patients with mildly impaired hearing or tinnitus must be made aware of potential ototoxicity and may choose not to be included. If included, it is recommended that audiograms be carried out at baseline.
- Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician's judgment, could interfere with patient safety or obtaining informed consent
- Known hepatitis B or C infection (testing for Hepatitis and HIV for the trial is not mandatory)
- Immunocompromised patients (e.g. known HIV positive status)
- Active uncontrolled infection
- The current use of drugs which are known to inhibit or induce CYP3A4
- Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- Patients with myelodysplastic syndrome/acute myeloid leukaemia.
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Guy's and St Thomas' NHS Foundation Trust
London
University College London Hospitals NHS Foundation Trust
London
Velindre Cancer Centre
Wales, CF14 2TL
About this study
Official title: A Phase I Trial of Olaparib in Addition to Cisplatin-based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (NHSCC)
The phase I trial aims to determine the recommended phase II dose (RP2D) and schedule of olaparib in combination with standard cisplatin-based chemoradiotherapy, in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (HNSCC), by assessing the safety and tolerability of the treatment combination.
Read the detailed description
ORCA-2 is a phase I trial in patients with locally advanced, with or without metastatic nodal disease.
Patients will receive olaparib (a PARP inhibitor) in combination with standard cisplatin-based chemotherapy and intensity modulated radiotherapy (IMRT).
Olaparib, cisplatin and radiotherapy will be given in combination every week for a maximum of 7 weeks. Prior to starting combination treatment, olaparib will be started 7 days before the first week of combination treatment. Olaparib will be given twice daily on days 1-3 of each week of treatment (either alone during week 0 or in combination with chemotherapy and radiotherapy during weeks 1-7). Cisplatin will be started on day 1 of each week, and given once a week during radiotherapy treatment for a total of 7 weeks. Radiotherapy will be delivered on days 1-5 of each week using IMRT, for a total of 7 weeks.
The phase I trial aims to determine the recommended phase II dose of olaparib (50mg, 100mg, 150mg or 200mg bd) - the dose of olaparib patients receive will depend on the dose under investigation at the time of patient registration.
Dose escalation will be guided by the two-dimensional dose escalation design called Product of Independent Beta Probabilities escalation (PIPE). It will recommend the choice of dose/duration combination cohort of olaparib for subsequent patients by estimating the contour that divides dose/duration combination cohorts to be those above the target toxicity rate (equal to 33%) and those below. The recommended phase II cohort(s) are those that have been experimented on during the trial and are also closest to (but not above) the estimated contour calculated using all trial data.
- Conditions
- Head and Neck Cancer
- Keywords
- Squamous Cell Carcinoma, Head and Neck Cancer, Locally Advanced, Olaparib, Cisplatin, IMRT, Chemoradiotherapy, PARP, HNSCC
- Medical subject headings
- Head and Neck Neoplasms, Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
50 mg, 100 mg, 150 mg or 200 mg taken twice daily (depending on dose under investigation at time of registration) on days 1-3, 1-4 or 1-5 (depending on allocation of treatment schedule) of each week of treatment.
CisplatinDrug
35 mg/m^2 IV on day 1 of each week of treatment during radiotherapy for a total of 7 weeks (total overall dose 245 mg/m^2)
IMRTRadiation
2 Gy delivered in 35 fractions, on days 1-3, 1-4 or 1-5 each week for up to 7 weeks (total overall dose delivered 70 Gy)
| Study group | Role | What they receive |
|---|---|---|
| Olaparib + Cisplatin + IMRT | Experimental | Olaparib: 50, 100, 150 or 200 mg twice a day for between 3-5 sequential days, depending on cohort allocation, in combination with Cisplatin: 35 mg/m^2 on day 1, and IMRT: 2 Gy radiotherapy given on days 1-5
Treatment will start on day 1 of every week. Patients will receive up to 7 weeks of combination chemotherapy and radiotherapy treatment. Receives: Drug: Olaparib; Drug: Cisplatin; Radiation: IMRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Dose Limiting Toxicity
Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be trial treatment related and commencing anytime during the DLT evaluation period (from start of week 1 of olaparib + CRT until 6 weeks after end of olaparib + CRT).
Measured: From start of week 1 to 6 weeks after end of combination treatment (combination treatment = 7 weeks)
Secondary outcomes (6)
Occurrence and Severity of Adverse Events
Will include all grade 1-5 adverse events
Measured: From date of registration until 12 weeks after completion of trial treatment
Best Overall Response
Response will be assessed according to RECIST v1.1. Confirmation of complete or partial response is not required.
Measured: Determined from imaging/scans performed pre-registration, during treatment and follow-up until disease progression or up to 2 years from date of registration
Time to Loco-Regional Progression
Time to loco-regional progression will be evaluated from the date of trial entry to date of documented disease progression according to RECIST v1.1 or histological/cytological confirmation.
Measured: From date of registration to date of documented disease progression, assessed up to 2 years from date of registration
Time to Progression
Time to progression will be determined from the date of patient registration to objective disease progression according to RECIST v1.1
Measured: From date of registration to date of documented objective disease progression
Progression Free Survival
Progression-free survival will be calculated from the date of trial entry to the date of documented disease progression, or death from any cause. Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used.
Measured: From date of registration to date of documented disease progression or death from any cause, whichever comes first. Assessed up to 2 years from date of registration.
Overall Survival
Overall survival time will be calculated from the date of trial entry to the date of death from any cause or end of trial follow-up.
Measured: From date of registration until date of death or date of last follow-up assessment (up to 2 years from date of registration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startSep 2015
- Primary completionJun 2020
- Study completion24 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Martin Forster, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308072
- Sponsor's protocol ID
- UCL/13/0696
- Other IDs
- 2014-002525-35, 2014
- Acronym
- ORCA-2
- Status last verified
- May 2026
- First submitted
- 2 Dec 2014
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Olaparib in Addition to Cisplatin-based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (NHSCC)
- ClinicalTrials.gov ID
- NCT02308072
- Acronym / sponsor ID
- ORCA-2 / UCL/13/0696
- Conditions
- Head and Neck Cancer
- Keywords
- Squamous Cell Carcinoma, Head and Neck Cancer, Locally Advanced, Olaparib, Cisplatin, IMRT, Chemoradiotherapy, PARP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Cancer Research UK, AstraZeneca
- Study start
- Sep 2015 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- 24 Apr 2026 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The phase I trial aims to determine the recommended phase II dose (RP2D) and schedule of olaparib in combination with standard cisplatin-based chemoradiotherapy, in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (HNSCC), by assessing the safety and tolerability of the treatment combination.
Detailed description
ORCA-2 is a phase I trial in patients with locally advanced, with or without metastatic nodal disease.
Patients will receive olaparib (a PARP inhibitor) in combination with standard cisplatin-based chemotherapy and intensity modulated radiotherapy (IMRT).
Olaparib, cisplatin and radiotherapy will be given in combination every week for a maximum of 7 weeks. Prior to starting combination treatment, olaparib will be started 7 days before the first week of combination treatment. Olaparib will be given twice daily on days 1-3 of each week of treatment (either alone during week 0 or in combination with chemotherapy and radiotherapy during weeks 1-7). Cisplatin will be started on day 1 of each week, and given once a week during radiotherapy treatment for a total of 7 weeks. Radiotherapy will be delivered on days 1-5 of each week using IMRT, for a total of 7 weeks.
The phase I trial aims to determine the recommended phase II dose of olaparib (50mg, 100mg, 150mg or 200mg bd) - the dose of olaparib patients receive will depend on the dose under investigation at the time of patient registration.
Dose escalation will be guided by the two-dimensional dose escalation design called Product of Independent Beta Probabilities escalation (PIPE). It will recommend the choice of dose/duration combination cohort of olaparib for subsequent patients by estimating the contour that divides dose/duration combination cohorts to be those above the target toxicity rate (equal to 33%) and those below. The recommended phase II cohort(s) are those that have been experimented on during the trial and are also closest to (but not above) the estimated contour calculated using all trial data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib + Cisplatin + IMRT | Experimental | Drug: Olaparib, Drug: Cisplatin, Radiation: IMRTOlaparib: 50, 100, 150 or 200 mg twice a day for between 3-5 sequential days, depending on cohort allocation, in combination with Cisplatin: 35 mg/m^2 on day 1, and IMRT: 2 Gy radiotherapy given on days 1-5 Treatment will start on day 1 of every week. Patients will receive up to 7 weeks of combination chemotherapy and radiotherapy treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed high-risk locally advanced HNSCC, patients who would normally be offered cisplatin-based radical chemoradiotherapy
- Estimated life expectancy of at least 16 weeks
- WHO performance status 0 or 1
- Aged ≥18 years
- Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0 or 1, haemoglobin grade 0 or 1
Key exclusion criteria (18 listed)
- Head \& neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, Oral squamous cell carcinomas (tumours of the oral cavity), Low risk Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
- Confirmed distant metastatic disease
- Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
- Previous therapy with a PARP inhibitor
- Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparib50 mg, 100 mg, 150 mg or 200 mg taken twice daily (depending on dose under investigation at time of registration) on days 1-3, 1-4 or 1-5 (depending on allocation of treatment schedule) of each week of treatment. | Drug | Olaparib + Cisplatin + IMRT |
| Cisplatin35 mg/m^2 IV on day 1 of each week of treatment during radiotherapy for a total of 7 weeks (total overall dose 245 mg/m^2) | Drug | Olaparib + Cisplatin + IMRT |
| IMRT2 Gy delivered in 35 fractions, on days 1-3, 1-4 or 1-5 each week for up to 7 weeks (total overall dose delivered 70 Gy) | Radiation | Olaparib + Cisplatin + IMRT |
Primary outcome
Occurrence of Dose Limiting Toxicity
Time frame: From start of week 1 to 6 weeks after end of combination treatment (combination treatment = 7 weeks)
Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be trial treatment related and commencing anytime during the DLT evaluation period (from start of week 1 of olaparib + CRT until 6 weeks after end of olaparib + CRT).
6 secondary outcomes
Occurrence and Severity of Adverse Events
Time frame: From date of registration until 12 weeks after completion of trial treatment
Best Overall Response
Time frame: Determined from imaging/scans performed pre-registration, during treatment and follow-up until disease progression or up to 2 years from date of registration
Time to Loco-Regional Progression
Time frame: From date of registration to date of documented disease progression, assessed up to 2 years from date of registration
Time to Progression
Time frame: From date of registration to date of documented objective disease progression
Progression Free Survival
Time frame: From date of registration to date of documented disease progression or death from any cause, whichever comes first. Assessed up to 2 years from date of registration.
Overall Survival
Time frame: From date of registration until date of death or date of last follow-up assessment (up to 2 years from date of registration)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Forster principal investigator
University College, London
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib, Cisplatin and IMRT in people with Head and Neck Cancer, run by University College, London at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Dose Limiting Toxicity (time frame: From start of week 1 to 6 weeks after end of combination treatment (combination treatment = 7 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.