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Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus (ROCOCO)

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ClinicalTrials.gov Identifier: NCT01460888
Recruitment Status : Unknown
Verified December 2011 by The Christie NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : October 27, 2011
Last Update Posted : August 19, 2013
Sponsor:
Collaborators:
Cancer Research UK
AstraZeneca
Information provided by:
The Christie NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE October 25, 2011
First Posted Date  ICMJE October 27, 2011
Last Update Posted Date August 19, 2013
Study Start Date  ICMJE July 2013
Estimated Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2011)
Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer [ Time Frame: 3 months post treatment ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2013)
  • Overall toxicity profile of treatment (NCRI Common Toxicity Criteria for Adverse Effects V3) [ Time Frame: Assessed at all study visits, up to 3 years post treatment. ]
    Toxicity of treatment will be assessed via collection of adverse events, categorised by the NCRI Common Toxicity Criteria for Adverse Effects (CTCAE) V3. Adverse event data will be collected continuously from screening, with patients seen weekly during their treatment, 10-14 days after treatment completion, weekly for 3 further weeks, 3 monthly until 1 year then 6 monthly until 3 years.
  • Olaparib compliance [ Time Frame: At completion of olaparib treatment (end of week 5) ]
  • Radiotherapy (RT) compliance [ Time Frame: At completion of RT treatment (end of week 5) ]
  • Local and overall treatment failure rate [ Time Frame: 3 months ]
    This is defined as residual disease pathologically on endoscopic assessment & biopsy or progressive disease on CT scan of thorax and abdomen.
  • Exploration of blood and tissue borne pharmacodynamic markers to establish the biological efficacy of the addition of Olaparib to radiotherapy. [ Time Frame: Up to 3 months post treatment ]
    • Endoscopic biopsy sample taken for analysis at screening & 3 months post treatment
    • Translational research blood samples taken at screening, weekly during treatment, at end of treatment visit & 3 months after treatment
    • Skin biopsy samples taken from within & outside irradiated field at week 4
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2011)
  • Overall toxicity profile of treatment (NCRI CTCAE V3) [ Time Frame: Assessed at all study visits, up to 3 years post treatment. ]
    Toxicity of treatment will be assessed via collection of adverse events, categorised by the NCRI CTCAE V3. Adverse event data will be collected continuously from screening, with patients seen weekly during their treatment, 10-14 days after treatment completion, weekly for 3 further weeks, 3 monthly until 1 year then 6 monthly until 3 years.
  • Olaparib compliance [ Time Frame: At completion of olaparib treatment (end of week 5) ]
  • Radiotherapy (RT) compliance [ Time Frame: At completion of RT treatment (end of week 5) ]
  • Local and overall treatment failure rate [ Time Frame: 3 months ]
    This is defined as residual disease pathologically on endoscopic assessment & biopsy or progressive disease on CT scan of thorax and abdomen.
  • Exploration of blood and tissue borne pharmacodynamic markers to establish the biological efficacy of the addition of Olaparib to radiotherapy. [ Time Frame: Up to 3 months post treatment ]
    • Endoscopic biopsy sample taken for analysis at screening & 3 months post treatment
    • Translational research blood samples taken at screening, weekly during treatment, at end of treatment visit & 3 months after treatment
    • Skin biopsy samples taken from within & outside irradiated field at week 4
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus
Official Title  ICMJE Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus. A Phase I Trial.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma of the Oesophagus
Intervention  ICMJE
  • Drug: Olaparib
    25mg tablets, oral. Commenced 3 days prior to radiotherapy and continuing until the last day of radiotherapy (36 days in total).
  • Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
    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.
Study Arms  ICMJE
  • Experimental: OLA-0 (de-escalation dose)
    25mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
    Interventions:
    • Drug: Olaparib
    • Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
  • Experimental: OLA-1
    50mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
    Interventions:
    • Drug: Olaparib
    • Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
  • Experimental: OLA-2
    100mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
    Interventions:
    • Drug: Olaparib
    • Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
  • Experimental: OLA-3
    200mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
    Interventions:
    • Drug: Olaparib
    • Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
  • Active Comparator: RT alone
    Intervention: Radiation: Radical external beam radiotherapy, 50Gy in 25 fractions
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 26, 2011)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2018
Estimated Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01460888
Other Study ID Numbers  ICMJE 10_DOG03_194
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE The Christie NHS Foundation Trust
Collaborators  ICMJE
  • Cancer Research UK
  • AstraZeneca
Investigators  ICMJE
Principal Investigator: Andrew Jackson, Dr University Hospital Southampton NHS Foundation Trust
PRS Account The Christie NHS Foundation Trust
Verification Date December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP