Synergism of Immunomodulation and Tumor Ablation
- Conditions
- Colorectal CancerLiver Metastases
- Interventions
- Radiation: Sterotactic body radiation therapy (SBRT)Other: Radiofrequency ablation (RFA)
- Registration Number
- NCT03101475
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description immunotherapy + local tumor ablation Durvalumab (MEDI4736) 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. immunotherapy + local tumor ablation Radiofrequency ablation (RFA) 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. immunotherapy + local tumor ablation Sterotactic body radiation therapy (SBRT) 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. immunotherapy + local tumor ablation Tremelimumab 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 Measures
Name Time Method Best overall immune response rate (iBOR) of lesions not treated by ablation/radiotherapy including the extrahepatic lesions according to iRECIST (with response confirmation) 36 months from first patient in The statistical design is based on the assumption that the continuation of first line systemic treatment would result in nearly no further response translating into a response rate of 0 to 5% at maximum in the enrolled patient's population. A response rate of 10% in the experimental arm (local treatment + immunotherapy) will be judged too low to justify this combined approach. On the contrary, a response rate of 25% will be judged very promising. An optimal Simon's two-stage design will be used for the rejection of a 10% or less iBOR rate
- Secondary Outcome Measures
Name Time Method Best overall immune response rate of liver lesions not treated with local therapy according to iRECIST (with response confirmation) 36 months from first patient in iBOR rate of liver lesions not treated with local therapy according to iRECIST (with response confirmation) will be displayed (point estimate) with their exact two-sided 95% confidence intervals.
Stable disease duration 54 months from first patient in Stable disease duration will be presented using the median, range (minimum, maximum) and inter-quartile range as well as the mean and standard deviation.
Overall survival 54 months from first patient in Overall survival curve will be estimated using the Kaplan-Meier technique. Medians will be displayed with their two-sided 95% confidence intervals.
Response duration 54 months from first patient in Response duration will be presented using the median, range (minimum, maximum) and inter-quartile range as well as the mean and standard deviation.
Safety: Safety analyses will be performed on the Safety population. The worst toxicity grade per patient over the treatment period according to the CTCAE criteria version 4.0 will be displayed. 54 months from first patient in Safety analyses will be performed on the Safety population. The worst toxicity grade per patient over the treatment period according to the CTCAE criteria version 4.0 will be displayed.
Best overall response rate of lesions not treated by ablation/radiotherapy including or not the extrahepatic lesions according to RECIST v1.1 (with response confirmation) 36 months from first patient in BOR rate of lesions not treated by ablation/radiotherapy including or not the extrahepatic lesions according to RECIST v1.1 (with response confirmation) will be displayed (point estimate) with their exact two-sided 95% confidence intervals.
Progression free survival according to iRECIST and to RECIST v1.1 54 months from first patient in Progression free survival according to iRECIST and RECIST v1.1 curve will be estimated using the Kaplan-Meier technique. Medians will be displayed with their two-sided 95% confidence intervals.
Trial Locations
- Locations (10)
Radboud University Medical Center Nijmegen
🇳🇱Nijmegen, Netherlands
Inselspital
🇨ðŸ‡Bern, Switzerland
Institut Bergonie
🇫🇷Bordeaux, France
Universitaetsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Medical University Vienna - General Hospital AKH
🇦🇹Vienna, Austria
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie
🇨ðŸ‡Geneva, Switzerland
UniversitaetsSpital Zurich
🇨ðŸ‡Zürich, Switzerland
Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden
🇩🇪Leipzig, Germany
Karolinska University Hospital - Karolinska Institutet - Danderyds Hospital
🇸🇪Stockholm, Sweden