Synergism of Immunomodulation and Tumor Ablation

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Study ID
NCT03101475
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • Durvalumab (MEDI4736) — DRUG
    Durvalumab (MEDI4736) 1500mg Q4W in combination with tremelimumab for up to 4 doses/cycles, followed by durvalumab (MEDI4736) 1500mg Q4W for up to a maximum of 8 months with the last administration on week 48 unless there is unacceptable toxicity.
  • Tremelimumab — DRUG
    Tremelimumab (75 mg IV Q4W) in combination with durvalumab (MEDI4736) (1500mg Q4W) for up to 4 doses/cycles
  • Sterotactic body radiation therapy (SBRT) — RADIATION
    delivered in 3 fractions of 10 Gy over 1 week starting 8 to 14 days after first dose of immunotherapy
  • Radiofrequency ablation (RFA) — OTHER
    performed percutaneously under CT, MRI or sonographic guidance 8 to 14 days after start of immunotherapy

Study Details

This is a single-arm, open-label, multi-center early phase II study. This proof of concept study will investigate whether the combined use of local tumor ablation/radiation plus immunomodulating drugs may induce a significant immune response in patient with incurable liver metastases from colorectal cancer (CRC) (+/- limited extrahepatic disease) being stable or in partial remission after completion of 4-6 months first line systemic therapy. The primary objective of the study is to show an overall response rate of lesions not treated by ablation/radiotherapy including the extrahepatic lesions (according to iRECIST criteria) higher than 10%. With the continuation of first line systemic treatment, no further responses are expected. Secondary objectives are: * To establish the feasibility and safety of the combined treatment modalities; * To study the impact of the local technique (RFA/Radiotherapy) on the results; * To investigate biomarkers to predict response to the combined treatment

Key Dates

Start date
Nov 23, 2018
Status verified
May 2022
Primary completion
Mar 3, 2021
Completion
Feb 23, 2022

Study Design

Enrollment
22 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: immunotherapy + local tumor ablation
    Patients with unresectable colorectal liver metastases which show at least stable disease or partial remission after 4-6 months will receive treatment with durvalumab and tremelimumab plus local tumor ablation (Radiofrequency ablation RFA or Sterotactic body radiation therapy SBRT) of selected liver lesions, followed by maintenance treatment with durvalumab.

Primary Outcome Measure

Best overall immune response rate (iBOR) of lesions not treated by ablation/radiotherapy including the extrahepatic lesions according to iRECIST (with response confirmation) [ Time Frame: 36 months from first patient in ]

Related Studies