Phase I Study of Olaparib With Cisplatin Based Chemoradio... | NCT01491139

Studies
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

NCT01491139

Sponsor

University College, London

Status

Withdrawn

Last Update Posted

May 30, 2012Estimated

Enrollment

0Actual

Phase

Phase 1

Conditions

Carcinoma, Squamous Cell

Interventions

olaparib
cisplatin
Intensity Modulated Radiotherapy

Countries

Not provided

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
62346992	Registry Identifier	ISRCTN

Status Module

Record Verification Date

May 2012

Overall Recruitment Status or Expanded Access Status

Withdrawn

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Study stopped due to issues surrounding development and formulation of olaparib

Expanded Access Info

Start Date

Not provided

Primary Completion Date

Not provided

Completion Date

Not provided

First Submitted Date

Dec 9, 2011

First Submission Date that Met QC Criteria

Dec 12, 2011

First Posted Date

Dec 13, 2011Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

May 29, 2012

Last Update Posted Date

May 30, 2012Estimated

Name	Class
AstraZeneca	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief 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. 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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

0Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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	Drug: olaparib Drug: cisplatin Radiation: Intensity Modulated Radiotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
olaparib	Drug	Given twice daily. Exposure will escalate by daily dose and duration.	single arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Frequency of dose limiting toxicities		6 weeks post completion of treatment

Secondary Outcomes

Measure	Description	Time Frame
Complete response rate		12 weeks post completion of treatment
Time to loco-regional progression		2 years post completion of treatment

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Name	Affiliation	Role
Martin D Forster, MBBS	University College London Hospitals	Principal Investigator

ID	Term
D002294	Carcinoma, Squamous Cell

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

Intervention Browse Module

MeSH Terms

ID	Term
C531550	olaparib
D002945	Cisplatin
D050397	Radiotherapy, Intensity-Modulated

Ancestor Terms

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

Browse Leaves

Not provided

Browse Branches

Not provided