Title

LUD2015-005

Chief Investigator: 

Sponsor: Ludwig Institute of Cancer Research

EudraCT number:  2015-005298-19

Phase 1/2 Study of anti-PD-L1 in Combination with Chemo(radio)therapy for Oesophageal Cancer

Open to recruitment

An open label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 & A2) and an expansion Phase 2 (Cohorts B, C & D).

Primary objectives

  • Assess the safety and tolerability of durvalumab alone and tremelimumab + durvalumab in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced OC.
  • Assess the safety and tolerability of durvalumab in combination with neoadjuvant chemo(radio)therapy in operable OC.

Participating Centres and target recruitment

  • Churchill Hospital
  • Southampton General Hospital

Total study sample size: 75

Recruitment expected to close March 2018

Study Schema

Synopsis of inclusion criteria

  1. Histological diagnosis of oesophageal or gastrooesophageal cancer.

-Cohorts A & B: metastatic or locally advanced cancer

-Cohorts C & D: deemed suitable for surgery with curative intent

  1. Recovered from prior therapy (persistent Grade 1 AEs are acceptable)
  2. Anticipated lifespan greater than 4 months
  3. ECOG performance status of 0 or 1
  4. Subjects with brain metastases must be asymptomatic for at least 4 weeks
  5. Adequate normal organ and marrow function, with laboratory parameters for vital functions in the normal range
  6. Written informed consent must be obtained prior to performing any protocol-related procedures
  7. 18 years or older of age
  8. Must have been informed of other treatment options
  9. Willing and able to comply with the protocol for the duration of the study

 

Synopsis of exclusion criteria

  1. Involvement in the planning and/or conduct of the study, or previous enrolment in the present study
  2. Participation in another clinical trial of an IMP within the last 6 weeks
  3. Prior or concurrent systemic anti-cancer therapy
  4. Mean QT interval corrected for heart heart rate (QTc) ≥ 470ms calculated from 3 ECGs using Fredericia’s Correction
  5. Current or prior use of immunosuppressive medication within 28 days prior to first dose of study drug (with some exceptions)
  6. Active or prior documented autoimmune disease within the past 2 years (excluding vitiligo, Grave’s disease or psoriasis that has not required systemic treatment in past 2 years)
  7. Active or prior documented inflammatory bowel disease
  8. History of allogeneic organ transplant
  9. Uncontrolled intercurrent illness
  10. Known history of previous clinical diagnosis of tuberculosis
  11. Receipt of live attenuated vaccination within 30 days prior to study entry or 30 days prior to receiving durvalumab
  12. Prior exposure to tremelimumab/durvalumab or checkpoint inhibitors
  13. History of severe allergic reactions
  14. Known DPD deficiency
  15. Treatment with sorivudine or chemically related analogues
  16. Peripheral sensitive neuropathy with functional impairment prior to first course
  17. History of sarcoidosis syndrome
  18. Metastatic disease to CNS for which other therapeutic options may be available, including radiotherapy
  19. History of pneumonitis or interstitial lung disease
  20. Major surgical procedure within 30 days of Day 1, or if still recovering from prior surgery.
  21. Women who are breast feeding or pregnant*
  22. Any condition that, in the clinical judgment of the treating physician, is likely  to interfere with the study*
  23. Subjects should not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or until the time specified in the prescribing information of oxaliplatin or capecitabine, whichever is longest
  24. For oxaliplatin and capecitabine, refer to prescribing information for additional information

Funding

The study is funded by the Ludwig Institute for Cancer Research

Data Capture

Data for this trial will be collection via Medidata RAVE®

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