Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

Sponsor
Ludwig Institute for Cancer Research
Study ID
NCT02735239
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Anti PD-L1 antibody
  • Tremelimumab — DRUG
    Anti CTLA-4 antibody
  • Oxaliplatin — DRUG
    IV administered chemotherapy
  • Capecitabine — DRUG
    orally-administered chemotherapy
  • Radiotherapy — RADIATION
  • Paclitaxel — DRUG
    IV administered chemotherapy
  • Carboplatin — DRUG
    IV administered Chemotherapy
  • 5-fluorouracil (5-FU) — DRUG
    IV administered chemotherapy
  • Leucovorin — DRUG
    chemo-protective agent
  • Docetaxel — DRUG
    IV administered chemotherapy

Study Details

This is 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 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2).

Key Dates

Start date
Jun 24, 2016
Status verified
Sep 2023
Primary completion
Jun 16, 2022
Completion
Jun 16, 2022

Study Design

Enrollment
73 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo)
    Durvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
  • Experimental: Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo
    Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
  • Experimental: Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo
    Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
  • Experimental: Cohort C: Operable OC; Durva + Chemo
    Durvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
  • Experimental: Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy
    Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
  • Experimental: Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy
    Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.

Primary Outcome Measure

Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) [ Time Frame: up to 1 year ]

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