Chief Investigator: Mark Middleton
Sponsor: Ludwig Institute of Cancer Research
EudraCT number: 2015-005298-19
Closed to recruitment
Lud2015-005 Trial Office
An open label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) (and tremelimumab for certain cohorts) 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).
- 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
- Ninewells Hospital, Dundee
- Nottingham City Hospital
Total study sample size: 75
Recruitment expected to close Dec 2019
Synopsis of inclusion criteria
- Histological diagnosis of oesophageal or gastrooesophageal cancer.
-Cohorts A & B: metastatic or locally advanced cancer
-Cohorts C, C-FLOT & D: deemed suitable for surgery with curative intent
- Recovered from prior therapy (persistent Grade 1 AEs are acceptable)
- Anticipated lifespan greater than 4 months
- ECOG performance status of 0 or 1
- Subjects with brain metastases must be asymptomatic for at least 4 weeks
- Adequate normal organ and marrow function, with laboratory parameters for vital functions in the normal range
- Written informed consent must be obtained prior to performing any protocol-related procedures, including protocol-specific screening evaluations
- 18 years or older of age
- Must have been informed of other treatment options
- Willing and able to comply with the protocol for the duration of the study
Synopsis of exclusion criteria
- Involvement in the planning and/or conduct of the study, or previous enrolment in the present study
- Prior treatment in another clinical trial with an IMP within the last 4 weeks
- Prior or concurrent systemic full-dose anti-cancer therapy
- Mean QT interval corrected for heart rate (QTc) ≥ 470ms calculated from 3 ECGs using Fredericia’s Correction
- 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)
- Active or prior documented inflammatory bowel disease
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness
- Known history of previous clinical diagnosis of tuberculosis
- Prior exposure to tremelimumab/durvalumab or checkpoint inhibitors
- History of severe allergic reactions to any unknown allergens or any components of the study drugs.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Treatment with sorivudine or chemically related analogues
- Peripheral sensitive neuropathy with functional impairment prior to first course
- History of sarcoidosis syndrome
- Metastatic disease to CNS for which other therapeutic options may be available, including radiotherapy
- History of pneumonitis or interstitial lung disease
- Major surgical procedure within 30 days of Day 1, or if still recovering from prior surgery.
- Women who are breast feeding or pregnant. Female subjects of childbearing potential and male subjects must who are sexually active with a female of childbearing potential must use at least one highly effective means of contraception. All subjects should be aware of the requirement to continue using highly effective means of contraception for several months after finishing study treatment.
- Any condition that, in the clinical judgment of the treating physician, is likely to interfere with the study.
- Subjects should not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or 6 months following last tremelimumab or until the time specified in the prescribing information of oxaliplatin, capecitabine, paclitaxel, carboplatin, 5-fluorouracil (5-FU), leucovorin or docetaxel, whichever is longest
- For oxaliplatin, capecitabine, paclitaxel, carboplatin, and FLOT (5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel): refer to prescribing information for additional information
The study is funded by the Ludwig Institute for Cancer Research
Data for this trial will be collection via Medidata RAVE®