Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Cisplatin

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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

Given twice daily. Exposure will escalate by daily dose and duration.

olaparib

cisplatin

Total dose will be 70Gy in 35 fractions over 7 weeks.

Intensity Modulated Radiotherapy

Martin D Forster, MBBS

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.

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.

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

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)

AstraZeneca

University College, London

Gemcitabine

Antimetabolites

AZD 2281

Giuseppe Giaccone, M.D.

Background:

* AZD2281 is an experimental drug in a class of agents called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage; PARP inhibitors interfere with that process.
* Cisplatin and gemcitabine are approved by the United States Food and Drug Administration to treat certain cancers.

Objectives:

* To determine the optimum doses of AZD2281, cisplatin and gemcitabine in combination that can safely be given to patients with solid tumor cancers.
* To evaluate the response of the tumor to the drug combination and determine the side effects of the treatment.

Eligibility:

-Patients 18 years or older with an advanced solid tumor cancer for whom standard treatments are not effective.

Design:

* In this dose escalation study, the first small group of patients receives the smallest study doses of the study drugs. Subsequent groups receive incrementally higher doses as long as the preceding group does not experience unacceptable side effects. When the highest safe dose is determined, additional patients entering the study receive that dose.
* Patients receive treatment in 21-day cycles as follows:
* Days 1-4: AZD2281 by mouth twice a day
* Day 3: gemcitabine thorough a vein over 1 hour; then cisplatin through a vein over 1 hour.
* Day 10: gemcitabine through a vein over 1 hour.
* Evaluations during treatment include the following:
* Physical examination, vital signs check and blood tests every 3 weeks.
* CT scans every 6 weeks to evaluate the tumor.
* Treatment may continue until it is no longer beneficial.

Background:

* Poly (ADP-ribose) polymerase-enzyme (PARP-1) recognizes and rapidly binds to DNA single- and double-strand breaks and has been shown to participate in other DNA-related functions, including gene amplification, cell division, differentiation, apoptosis, and DNA base-excision repair.
* Increased PARP activity is one of the mechanisms by which tumor cells avoid apoptosis caused by DNA damaging agents, and drug resistance has been linked to higher expressions of PARP in cancer cells. This differential expression of PARP supports the observed selectivity of PARP inhibitors to affect proliferating tumor cells. AZD2281 is an orally administered potent inhibitor of PARP-1 and PARP-2, and its combination with cisplatin and gemcitabine may overcome some of the resistance associated with these agents.

Primary Objectives:

* Establish the safety, tolerability, and maximum tolerated dose (MTD) of AZD2281 in combination with cisplatin and gemcitabine in patients with solid tumors.
* Evaluate the effect of cisplatin-gemcitabine, with or without AZD2281, on PAR and gamma- H2AX levels in tumor biopsies and peripheral blood mononuclear cells (PBMCs) pre- and post-treatment.

Secondary Objectives:

- Evaluate the pharmacokinetics (PK) of AZD2281 with and without cisplatin and gemcitabine.

Eligibility:

* Patients (greater than or equal to 18 years) must have histologically confirmed solid tumor malignancy that is metastatic or unresectable for which standard curative measures do not exist, or are associated with minimal patient survival benefit.
* Patients who have previously received cisplatin or gemcitabine, or both, are eligible.

Design:

* Cycle 1 and subsequent cycles: AZD2281 will be administered orally every 12 hours (Q 12 hours) on day 1, while gemcitabine will be administered intravenously (IV) over 1 hour (600 mg/m(2)/hour) on day 1 and 8 of each cycle and cisplatin over 1 hour on day 1 after gemcitabine.
* Dose escalation will proceed in cohorts of 3 6 patients to a minimum of 27 and a maximum of 42 patients.
* Patients will have a maximum of six cycles of treatment.
* Tumor biopsies will be collected in cycle 1 only, while blood for PBMC samples will be collected in cycle 1 and before drug administration, 24 and 48 hours post administration, in cycle 2, day 1. If Dose Level 3 is achieved additional time points will be collected in cycle 1, day 8 - before drug administration, 6, 24 and 48 hours

post.

AZD2281 and Cisplatin Plus Gemcitabine to Treat Solid Tumor Cancers

A Phase I Combination Study of AZD2281 and Cisplatin Plus Gemcitabine in Adults With Solid Tumors

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck	NCT01491139	Carcinoma, Squa...	olaparib cisplatin Intensity Modul...	18 Years -	University College, London
AZD2281 and Cisplatin Plus Gemcitabine to Treat Solid Tumor Cancers	NCT00678132	Neoplasms	AZD 2281 Cisplatin Gemcitabine	18 Years -	National Institutes of Health Clinical Center (CC)
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck	NCT01491139	Carcinoma, Squa...	olaparib cisplatin Intensity Modul...	18 Years -	University College, London

Spots Global Cancer Trial Database for azd 2281

Every month we try and update this database with for azd 2281 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd 2281

Every month we try and update this database with for azd 2281 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd 2281 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.