A Trial of Durvalumab (MEDI 4736) in Combination With Extended Neoadjuvant Regimens in Rectal Cancer

Sponsor
Liz-Anne Lewsley
Study ID
NCT04621370
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

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

Interventions

  • Durvalumab — DRUG
    Flat dose of 1500mg delivered intravenously over 30 minutes every 4 weeks.
  • FOLFOX — DRUG
    Oxaliplatin 85mg/m2 delivered intravenously as per institutional standard on Day 1 of mFOLFOX6 treatment every 2 weeks. 5-fluorouracil bolus 400mg/m2 delivered intravenously as per institutional standard on D1 of mFOLFOX6 treatment every 2 weeks. 5-fluorouracil infusion 2400mg/m2 delivered intravenously over 46 hours continuously as per institutional standard following bolus 5-fluorouracil.
  • Short Course Radiotherapy (Arm A) — RADIATION
    25 Gray of photon radiation treatment delivered over 5 fractions.
  • Long course chemoradiation (Arm B) — RADIATION
    50 Gray of photon radiation treatment delivered over 25 fractions.
  • Capecitabine — DRUG
    Capecitabine is a non-cytotoxic pre-cursor of cytotoxic 5-fluorouracil and delivered in oral form. It is given concomitantly with long course radiation treatment on days of radiotherapy only. The dose is 825mg/m2 and this is delivered twice daily.

Study Details

PRIME-RT is an open label, multi-centre phase II randomised trial with 1:1 allocation between arm A and arm B. The principal research question is whether the addition of durvalumab to FOLFOX chemotherapy and radiation treatment (either SCRT or LCRT) in the neoadjuvant setting for patients with locally advanced rectal cancer (LARC) improves rates of complete response. The working hypothesis is that the use of radiation and cytotoxic chemotherapy may prime the tumour immune microenvironment for treatment with immune checkpoint blockade. The main trial will commence after completion of a safety run-in which will enrol at least three patients per arm to test the safety and tolerability of the treatment combinations in each.

Key Dates

Start date
Dec 7, 2020
Status verified
Nov 2020
Primary completion
Jun 30, 2025
Completion
Dec 31, 2025

Study Design

Enrollment
48 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A
    * Durvalumab 1500mg IV over 60 minutes, starting in the week prior to day 1 of radiotherapy, and continuing every 4 weeks until completion of FOLFOX chemotherapy * Short course radiotherapy (25Gy delivered in 5 fractions) starting on day 1 * FOLFOX chemotherapy will be given every 2 weeks, starting approximately 1-2 weeks after radiotherapy and continuing for 6 cycles in total * Assessment of response will be at approximately 16-18 weeks after day 1 of RT. If the patient is proceeding to surgery, this will be performed at approximately 18-20 weeks after day 1 of RT where possible.
  • Active Comparator: Arm B
    * Durvalumab 1500mg IV over 60 minutes, starting in the week prior to day 1 of radiotherapy, and continuing every 4 weeks until completion of FOLFOX chemotherapy * Long course chemoradiotherapy (50Gy to boost volume, 45Gy to elective volume delivered in 25 fractions) starting on day 1 * FOLFOX chemotherapy will be given every 2 weeks, starting approximately 1-2 weeks after radiotherapy for 4 cycles * Assessment of response at approximately 16-18 weeks after day 1 of RT. If the patient is proceeding to surgery, this will be performed at approximately 18-20 weeks after day 1 of RT where possible.

Primary Outcome Measure

Complete response [ Time Frame: 6 months ]

Central Contacts

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