Study Title: Peri-operative Immuno-Chemotherapy in Operable Oesophageal and Gastric Cancer (ICONIC)
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|ClinicalTrials.gov Identifier: NCT03399071|
Recruitment Status : Recruiting
First Posted : January 16, 2018
Last Update Posted : February 12, 2018
A single centre phase II trial of peri-operative chemo-immunotherapy in operable gastro-oesophageal adenocarcinoma (GOA). This trial is designed to evaluate the safety and efficacy of administering Avelumab, an anti-PD-L1 monoclonal antibody, with cytotoxic FLOT chemotherapy for patients with operable GOA treated according to a peri-operative protocol.
This trial is in 2 stages: the first stage will establish the safe and tolerated maximum administered dose (MAD) of Avelumab in combination with FLOT and the second stage will assess the efficacy of this combination therapy in achieving pathological complete response (pCR) and peri-operative safety.
|Condition or disease||Intervention/treatment||Phase|
|Gastric Adenocarcinoma Oesophageal Adenocarcinoma||Drug: FLOT-A||Phase 2|
Patients will receive chemo-immunotherapy consisting of FLOT chemotherapy (Folinic acid 200mg/m2 iv infusion day 1, Oxaliplatin 85mg/m2 iv infusion day 1, Docetaxel 50mg/m2 iv day 1, Fluorouracil 2600mg/m2 over 24 hours iv) and the PD-L1 inhibiting monoclonal antibody Avelumab. The safe dose of Avelumab in combination with FLOT will be established in a safety run-in phase with a standard 3+3 design, starting with the recommended dose of 10mg/kg iv Avelumab (dose level 0) in which a dose reduction to 7mg/kg iv (dose level -1) may occur. Four cycles of two-weekly chemo-immunotherapy will be administered before surgery and four further cycles post-operatively in patients who are fit enough to receive further chemo-immunotherapy after surgery. Resectional surgery will take place 4-8 weeks following the last dose of chemo-immunotherapy in patients who remain fit.
To evaluate the safety, efficacy and toxicities and to explore biomarkers of peri-operative chemo-immunotherapy with Avelumab and FLOT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||All patients will receive chemo-immunotherapy consisting of FLOT chemotherapy and the PD-L1 inhibiting monoclonal antibody Avelumab. Four cycles of two-weekly chemo-immunotherapy will be administered before surgery and four further cycles post-operatively in patients who are fit enough to receive further chemo-immunotherapy after surgery. Resectional surgery will take place 4-8 weeks following the last dose of chemo-immunotherapy in patients who remain fit.|
|Masking:||None (Open Label)|
|Official Title:||Study Title: Peri-operative Immuno-Chemotherapy in Operable Oesophageal and Gastric Cancer (ICONIC Trial)|
|Actual Study Start Date :||July 31, 2017|
|Estimated Primary Completion Date :||April 15, 2021|
|Estimated Study Completion Date :||August 15, 2025|
Experimental: FLOT plus Avelumab (FLOT-A)
Avelumab 10mg/kg (or Maximum Administered Dose established in safety run-in) iv infusion over 1 hour.
Followed by FLOT: Oxaliplatin 85mg/m2 iv infusion day 1 over 2 hours, Folinic acid 200mg/m2 iv infusion day 1 over 2 hours, Docetaxel 50mg/m2 iv day 1 over 1 hour, Fluorouracil 2600mg/m2 over 24 hours iv
This is a single-arm study with all patients receiving combination FLOT-A
- Pathological complete response rate of combination FLOT-A [ Time Frame: Within 2 years of study opening ]
The primary objective is to assess the efficacy of FLOT-A in the peri-operative setting in patients with operable GOAs. We aim to increase the pCR rate after peri-operative treatment from 10% (minimum expected path CR rate for peri-operative FLOT chemotherapy), to a superior pCR rate of >25%, by adding Avelumab to FLOT.
Complete histopathologic response is defined by no vital tumour cells neither in the oesophagus, the stomach nor in the regional lymph nodes. In cases of residual tumour, the response assessment will follow criteria described by Mandard et al.
- Number of participants with grade 3 or 4 treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Within 2 years ]Safety of peri-operative FLOT-A will be assessed by summarising grade 3-4 toxicity and DLT rates as proportions.
- Radiological response rate using RECIST 1.1 criteria [ Time Frame: Within 3 years ]Radiological response rate assessed at the pre-operative scan using RECIST 1.1 criteria. Radiological tumour response before surgery will be defined as partial response or complete response.
- Median progression free survival by Kaplan Meir method [ Time Frame: Within 5 years ]PFS will be summarised using Kaplan Meier methods, presenting median survival with 95% confidence intervals. PFS is defined as time from registration to clinical/radiological progression or death from any cause. Patients event free at time of analysis will be censored at last follow-up date.
- Median overall survival by Kaplan Meir method [ Time Frame: Within 5 years ]OS will be summarised using Kaplan Meier method, presenting median survival with 95% confidence intervals. OS is defined as time from registration to date of death of any cause. Patients event free at time of analysis will be censored at last follow-up date.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399071
|Contact: Marco Gerlinger, MD, FRCPfirstname.lastname@example.org|
|The Royal Marsden Hospital||Recruiting|
|London, United Kingdom, SW3 6JJ|
|Contact: Marco Gerlinger, MD, FRCP 02071535234 email@example.com|