Carcinoma, Squamous CellPhase 1ORCANCT01491139
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck
A Phase 1 study testing olaparib, cisplatin and Intensity Modulated Radiotherapy in people with Carcinoma, Squamous Cell, run by University College, London.
Trial summary
The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Squamous Cell
- What is being tested?
- olaparib, cisplatin and Intensity Modulated Radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- 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 (TNM staging: T-any N2/3 M0, bulky T3 or T4 N-any M0) who would normally be offered cisplatin-based radical chemoradiotherapy
- Estimated life expectancy of at least 12 weeks
- WHO performance status of 0 or 1
- Aged ≥18 years of age
- Adequate major organ function
- Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
- Able to give informed consent
- 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),
- 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
Show all 11Show fewer
- Previous therapy with a PARP inhibitor
- Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
- Grade 3 or 4 peripheral neuropathy
- Significant hearing difficulties or tinnitus (deaf patients can be included)
- The current use of drugs which are known to inhibit or induce CYP3A4
About this study
Official 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)
The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.
Read the detailed description
This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.
This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.
Patients will be recruited from sites in the UK only.
A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.
- Conditions
- Carcinoma, Squamous Cell
- Keywords
- Radiotherapy, Biomarkers, pharmacological, Pharmacokinetics, Genetic Markers, Cisplatin, Poly(ADP-ribose) Polymerases, AZD 2281, Radiotherapy, Intensity-Modulated, Head and Neck, Chemoradiotherapy, SCC
- Medical subject headings
- Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olaparibDrug
Also called AZ2281
Given twice daily. Exposure will escalate by daily dose and duration.
cisplatinDrug
Dose will be 35mg/m2 i.v. once weekly.
Intensity Modulated RadiotherapyRadiation
Total dose will be 70Gy in 35 fractions over 7 weeks.
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.
Induction chemotherapy (21 day cycle)
* Drug: cisplatin 80mg/m2 (day 1)
* Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)
olaparib plus chemoradiotherapy (8 weeks)
* Drug: olaparib
* Drug: Cisplatin
* Radiation Receives: Drug: olaparib; Drug: cisplatin; Radiation: Intensity Modulated Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of dose limiting toxicities
Measured: 6 weeks post completion of treatment
Secondary outcomes (2)
Complete response rate
Measured: 12 weeks post completion of treatment
Time to loco-regional progression
Measured: 2 years post completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
Why it stopped: Study stopped due to issues surrounding development and formulation of olaparib
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Squamous CellStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Martin D Forster, MBBS, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01491139
- Sponsor's protocol ID
- 2010-023599-24
- Other IDs
- 62346992
- Acronym
- ORCA
- Status last verified
- May 2012
- First submitted
- 9 Dec 2011
- Last updated
- 30 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT01491139
- Acronym / sponsor ID
- ORCA / 2010-023599-24
- Conditions
- Carcinoma, Squamous Cell
- Keywords
- Radiotherapy, Biomarkers, pharmacological, Pharmacokinetics, Genetic Markers, Cisplatin, Poly(ADP-ribose) Polymerases, AZD 2281, Radiotherapy, Intensity-Modulated
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study stopped due to issues surrounding development and formulation of olaparib
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- First posted
- 13 Dec 2011 (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 aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.
Detailed description
This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.
This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.
Patients will be recruited from sites in the UK only.
A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: olaparib, Drug: cisplatin, Radiation: Intensity Modulated RadiotherapyAll patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib. Induction chemotherapy (21 day cycle) * Drug: cisplatin 80mg/m2 (day 1) * Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion) olaparib plus chemoradiotherapy (8 weeks) * Drug: olaparib * Drug: Cisplatin * Radiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed high risk, locally advanced HNSCC patients (TNM staging: T-any N2/3 M0, bulky T3 or T4 N-any M0) who would normally be offered cisplatin-based radical chemoradiotherapy
- Estimated life expectancy of at least 12 weeks
- WHO performance status of 0 or 1
- Aged ≥18 years of age
- Adequate major organ function
Key exclusion criteria (11 listed)
- Head \& neck cancers of the following types:
- Nasopharyngeal and paranasal sinus tumours,
- Oral squamous cell carcinomas (tumours of the oral cavity),
- Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
- Confirmed distant metastatic disease
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 |
|---|---|---|
| olaparibAlso: AZ2281Given twice daily. Exposure will escalate by daily dose and duration. | Drug | single arm |
| cisplatinDose will be 35mg/m2 i.v. once weekly. | Drug | single arm |
| Intensity Modulated RadiotherapyTotal dose will be 70Gy in 35 fractions over 7 weeks. | Radiation | single arm |
Primary outcome
Frequency of dose limiting toxicities
Time frame: 6 weeks post completion of treatment
2 secondary outcomes
Complete response rate
Time frame: 12 weeks post completion of treatment
Time to loco-regional progression
Time frame: 2 years post completion of treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2012.
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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 D Forster, MBBS principal investigator
University College London Hospitals
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing olaparib, cisplatin and Intensity Modulated Radiotherapy in people with Carcinoma, Squamous Cell, run by University College, London.
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 8 inclusion and 11 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: withdrawn, as of the sponsor's last update on 30 May 2012. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Frequency of dose limiting toxicities (time frame: 6 weeks post completion of treatment). 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 30 May 2012.