Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus

Trial Title: Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus

NCT ID: NCT01460888

Condition: Carcinoma of the Oesophagus

Conditions: Official terms:
Carcinoma
Esophageal Neoplasms
Olaparib

Study type: Interventional

Study phase: Phase 1

Overall status: Unknown status

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Olaparib
Description: 25mg tablets, oral. Commenced 3 days prior to radiotherapy and continuing until the last day of radiotherapy (36 days in total).
Arm group label: OLA-0 (de-escalation dose)
Arm group label: OLA-1
Arm group label: OLA-2
Arm group label: OLA-3

Intervention type: Radiation
Intervention name: Radical external beam radiotherapy, 50Gy in 25 fractions
Description: 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.
Arm group label: OLA-0 (de-escalation dose)
Arm group label: OLA-1
Arm group label: OLA-2
Arm group label: OLA-3
Arm group label: RT alone

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus including Siewert type 1 or 2 tumours with ≤2cm gastric mucosal extension 2. Unsuitable for radical chemoradiation therapy but suitable for radiotherapy 3. Total length of tumour and involved lymph nodes ≤10cm 4. No oesophageal stent in situ 5. No previous chemotherapy or radiotherapy for oesophagus cancer 6. Disease which can be encompassed within a radical radiotherapy treatment volume 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see ECOG criteria appendix 1) 8. Provision of fully informed consent, signed, written and dated, prior to any study specific procedures. 9. > 18 years of age. 10. 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 - Total bilirubin ≤ 1.5 x institutional upper limit of normal - Aspartate aminotransferase (AST(SGOT)/Alanine transaminase (ALT)SGPT) ≤ 2.5 x institutional upper limit of normal - Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) 11. Adequate lung function: no history of interstitial lung disease and FEV1 > 1litre and >30% predicted. 12. Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Postmenopausal is defined as: - Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments - Luteinizing hormone(LH) and Follicle-stimulating hormone (FSH) levels in the post menopausal range for women under 50, - radiation-induced oophorectomy with last menses >1 year ago, - chemotherapy-induced menopause with >1 year interval since last menses, - surgical sterilisation (bilateral oophorectomy or hysterectomy). 13. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 14. Fit to receive all study treatments 15. Swallowing sufficiently good to tolerate oral medication 16. Life expectancy ≥ 4 months. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous enrolment in the present study 3. Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used) 4. Any previous treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, including olaparib. 5. 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. 6. Patients receiving the following classes of inhibitors of cytochrome P450 3A4 (CYP3A4) - Azole antifungals - Macrolide antibiotics - Protease inhibitors 7. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 8. 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. 9. 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. 10. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 11. Patients with oesophageal stent in-situ 12. Patients with myelodysplastic syndrome/acute myeloid leukaemia 13. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 14. Patients with known active hepatic disease (i.e., Hepatitis B or C). 15. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 16. Patients with uncontrolled seizures. 17. Concurrent uncontrolled medical illness, or other previous or current malignant disease likely to interfere with protocol treatments / comparisons 18. Age < 18 19. Any pregnant, lactating women or potentially childbearing patients not using adequate contraception (see section 3.4 for details of required contraception). 20. Previous chemotherapy or radiotherapy for oesophageal cancer 21. Metastatic disease apart from local lymph node disease which can be reasonably encompassed within the radiotherapy volume (total length of tumour and lymph node disease should be <10cm) 22. ECOG performance status >2

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: The Christie NHS Foundation Trust

Address:
City: Manchester
Zip: M20 4BX
Country: United Kingdom

Status: Not yet recruiting

Investigator:
Last name: Hamid Shiekh, Dr
Email: Principal Investigator

Facility:
Name: Southampton General Hospital

Address:
City: Southampton
Zip: SO16 6YD
Country: United Kingdom

Status: Recruiting

Contact:
Last name: Andrew Jackson, MD

Phone: +44(0)2380795386
Email: Andrew.Jackson@uhs.nhs.uk

Investigator:
Last name: Andrew Jackson, Dr
Email: Principal Investigator

Start date: July 2013

Completion date: August 2018

Lead sponsor:
Agency: The Christie NHS Foundation Trust
Agency class: Other

Collaborator:
Agency: Cancer Research UK
Agency class: Other

Collaborator:
Agency: AstraZeneca
Agency class: Industry

Source: The Christie NHS Foundation Trust

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT01460888