Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus

NCT01460888 | Unknown Phase 1 DMC

• 1 other identifier: 10_DOG03_194
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer who are unsuitable for platinum containing chemotherapy.

Conditions

Carcinoma of the Oesophagus

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer

  MTD will be determined by the number of patients experiencing dose limiting toxicities (DLTs) in each treatment cohort, using a 3+3 dose escalation schedule. A DLT is determined as grade 4 oesophagitis or dysphagia, or any other grade 3 toxicity. DLTs will be assessed weekly during treatment (day -3 to week 5), 10-14 days after completing treatment, weekly for a further 3 weeks and 3 months after completing treatment.

  3 months post treatment

Secondary Outcomes (5)

• Overall toxicity profile of treatment (NCRI Common Toxicity Criteria for Adverse Effects V3)

  Assessed at all study visits, up to 3 years post treatment.

• Olaparib compliance

  At completion of olaparib treatment (end of week 5)

• Radiotherapy (RT) compliance

  At completion of RT treatment (end of week 5)

• Local and overall treatment failure rate

  3 months

• Exploration of blood and tissue borne pharmacodynamic markers to establish the biological efficacy of the addition of Olaparib to radiotherapy.

  Up to 3 months post treatment

Study Arms (5)

OLA-0 (de-escalation dose)

EXPERIMENTAL

25mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)

Drug: Olaparib; Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions

OLA-1

EXPERIMENTAL

50mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)

Drug: Olaparib; Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions

OLA-2

EXPERIMENTAL

100mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)

Drug: Olaparib; Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions

OLA-3

EXPERIMENTAL

200mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)

Drug: Olaparib; Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions

RT alone

ACTIVE COMPARATOR

Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions

Interventions

Olaparib DRUG

25mg tablets, oral. Commenced 3 days prior to radiotherapy and continuing until the last day of radiotherapy (36 days in total).

OLA-0 (de-escalation dose); OLA-1; OLA-2; OLA-3

Radical external beam radiotherapy, 50Gy in 25 fractions RADIATION

Radiotherapy to the oesophageal carcinoma. For patients receiving olaparib this is delivered as 50Gy in 25 daily fractions for 5 weeks (Monday-Friday only). For patients in the comparator arm (RT only) other total doses/ fractionation are permitted, according to local policy/ best standard care.

OLA-0 (de-escalation dose); OLA-1; OLA-2; OLA-3; RT alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus including Siewert type 1 or 2 tumours with ≤2cm gastric mucosal extension
• Unsuitable for radical chemoradiation therapy but suitable for radiotherapy
• Total length of tumour and involved lymph nodes ≤10cm
• No oesophageal stent in situ
• No previous chemotherapy or radiotherapy for oesophagus cancer
• Disease which can be encompassed within a radical radiotherapy treatment volume
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see ECOG criteria appendix 1)
• Provision of fully informed consent, signed, written and dated, prior to any study specific procedures.
• \> 18 years of age.
• Adequate organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) \> 3 x 109/L
• Platelet count ≥ 100 x 109/L
• No dysplastic features on peripheral blood smear

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrolment in the present study
• Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
• Any previous treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, including olaparib.
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
• Patients receiving the following classes of inhibitors of cytochrome P450 3A4 (CYP3A4)
• Azole antifungals
• Macrolide antibiotics
• Protease inhibitors
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, or any psychiatric disorder that prohibits obtaining informed consent.
• Patients with a history of interstitial lung disease, inflammatory lung conditions, or severe chronic obstructive pulmonary disease (COPD) (FEV1\<1litre or \< 30% predicted). Patients with pneumonia within the previous 3 months.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Patients with oesophageal stent in-situ
• Patients with myelodysplastic syndrome/acute myeloid leukaemia

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Cancer Research UK: collaborator
• AstraZeneca: collaborator

Study Sites (2)

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

NOT YET RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Andrew Jackson, Dr

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ian Emerson, Mr

CONTACT

+44 (0)161 918 7443; ian.emerson@christie.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: October 27, 2011
• Study Start: July 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2018
• Last Updated: August 19, 2013

Record last verified: 2011-12

Locations

GB (2)