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Clinical Trial Evaluating FOLFIRI + Durvalumab vs FOLFIRI + Durvalumab and Tremelimumab in Second-line Treatment of Patients With Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma

NCT03959293

Description:

Gastric adenocarcinoma is the 4th most frequent cancer and the 2nd leading cause of cancer mortality. Most of the patients have metastatic, locally advanced or recurrent unresectable disease. So, systemic treatment remains an important issue especially since chemotherapy improves survival and quality of life (compared to best supportive care alone). Second-line chemotherapy-based treatment improves overall survival (OS) as compared to best supportive care alone in patients with an acceptable general condition (performance status 0-2). Indeed, with docetaxel monotherapy there was a significant difference in overall survival for the chemotherapy arm with a median of 5.2 versus 3.6 months in best supportive care alone arm (HR=0.67, p=0.01). Irinotecan monotherapy also significantly improves overall survival compared to supportive care alone in a phase III study (4.0 versus 2.4 months; HR=0.48, 95%CI 0.25-0.92; p=0.012). Based on a phase III trial FOLFIRI (5-FU plus irinotecan) is one most used regimen in second-line in European countries, especially in France. FFCD 0307 trial, a phase III comparing FOLFIRI-ECX (epirubicin-cisplatin-capecitabine) to the reverse sequence (ECX-FOLFIRI), showed that both sequences are possible. Preliminary results in metastatic gastric cancer with anti-PD1 mAbs are highly promising. In a trial with pembrolizumab, only PD-L1 positive tumors were eligible to the treatment with a cut off at 1%. Thirty-nine patients were enrolled and 67% had received at least two prior chemotherapy regimens. The overall response rate was 22%. The median PFS and OS were 1.9 months and 11.4 months, respectively. KEYNOTE-059 Phase 2 multicohort study with pembrolizumab monotherapy in advanced gastric cancer treatment has been presented at ASCO 2017 meeting. Among 259 patients included in the trial response rate was 11.6%. OS was 5.6 months. Response rates were 15.5% in PDL1+ tumors versus 6.4% in PDL1- tumors and 57.1% in MSI tumors versus 9% in MSS tumors. Up until now, overlap between microsatellite instability and PD-L1 expression is unknown in gastric cancer. An anti-PD-L1 mAb (avelumab) was evaluated in a phase Ib expansion study (n=20, Japanese patients), with 15% of objective response rate and 11.9 weeks for progression-free survival. A second cohort with avelumab included 55 patients for maintenance therapy after first-line chemotherapy, with 7.3% of objective response rate and 14 weeks of PFS. Phase I/II CheckMate-032 evaluated nivolumab (anti-PD-1) ± ipilimumab (anti-CTLA4) at different doses in advanced gastric cancer (17). The overall response rate was between 8% to 24% and the median OS between 4.8 to 6.9 months according to treatment arm. Others anti-PD1/anti-PD-L1/anti-CTLA4 mAbs are also currently under investigation in gastric cancer alone or in combination with chemotherapy. Nevertheless, up until now there is no published data concerning ICI plus chemotherapy in gastric cancer. The present randomized multicentric non-comparative phase II study aimed to assess the rate of patients alive and without progression at 4 months with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma, pre-treated with fluoropyrimidine + platinum +/- taxane, with two arms Folfiri plus durvalumab versus Folfiri plus durvalumab plus tremelimumab. Indeed, most patients in the French multicentric first-line GASTFOX trial (506 patients planned between 2017 and 2020) can be included in the second-line setting in the DURIGAST trial. Due to the lack of data concerning Folfiri plus durvalumab plus tremelimumab combination, a safety run-in phase will be performed at the beginning of the DURIGAST trial.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial Evaluating FOLFIRI + Durvalumab vs FOLFIRI + Durvalumab and Tremelimumab in Second-line Treatment of Patients With Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma
  • Official Title: A Randomized Phase II Study Evaluating FOLFIRI + Durvalumab vs FOLFIRI + Durvalumab and Tremelimumab in Second-line Treatment of Patients With Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: PRODIGE 59 - DURIGAST
  • SECONDARY ID: FFCD 1707
  • SECONDARY ID: 2018-002014-13
  • NCT ID: NCT03959293

Conditions

  • Gastric Adenocarcinoma
  • Gastric Cancer

Interventions

DrugSynonymsArms
DurvalumabFOLFIRI plus durvalumab
TremelimumabFOLFIRI plus durvalumab plus tremelimumab
FOLFIRI ProtocolFOLFIRI plus durvalumab

Purpose

Gastric adenocarcinoma is the 4th most frequent cancer and the 2nd leading cause of cancer mortality. Most of the patients have metastatic, locally advanced or recurrent unresectable disease. So, systemic treatment remains an important issue especially since chemotherapy improves survival and quality of life (compared to best supportive care alone). Second-line chemotherapy-based treatment improves overall survival (OS) as compared to best supportive care alone in patients with an acceptable general condition (performance status 0-2). Indeed, with docetaxel monotherapy there was a significant difference in overall survival for the chemotherapy arm with a median of 5.2 versus 3.6 months in best supportive care alone arm (HR=0.67, p=0.01). Irinotecan monotherapy also significantly improves overall survival compared to supportive care alone in a phase III study (4.0 versus 2.4 months; HR=0.48, 95%CI 0.25-0.92; p=0.012). Based on a phase III trial FOLFIRI (5-FU plus irinotecan) is one most used regimen in second-line in European countries, especially in France. FFCD 0307 trial, a phase III comparing FOLFIRI-ECX (epirubicin-cisplatin-capecitabine) to the reverse sequence (ECX-FOLFIRI), showed that both sequences are possible. Preliminary results in metastatic gastric cancer with anti-PD1 mAbs are highly promising. In a trial with pembrolizumab, only PD-L1 positive tumors were eligible to the treatment with a cut off at 1%. Thirty-nine patients were enrolled and 67% had received at least two prior chemotherapy regimens. The overall response rate was 22%. The median PFS and OS were 1.9 months and 11.4 months, respectively. KEYNOTE-059 Phase 2 multicohort study with pembrolizumab monotherapy in advanced gastric cancer treatment has been presented at ASCO 2017 meeting. Among 259 patients included in the trial response rate was 11.6%. OS was 5.6 months. Response rates were 15.5% in PDL1+ tumors versus 6.4% in PDL1- tumors and 57.1% in MSI tumors versus 9% in MSS tumors. Up until now, overlap between microsatellite instability and PD-L1 expression is unknown in gastric cancer. An anti-PD-L1 mAb (avelumab) was evaluated in a phase Ib expansion study (n=20, Japanese patients), with 15% of objective response rate and 11.9 weeks for progression-free survival. A second cohort with avelumab included 55 patients for maintenance therapy after first-line chemotherapy, with 7.3% of objective response rate and 14 weeks of PFS. Phase I/II CheckMate-032 evaluated nivolumab (anti-PD-1) ± ipilimumab (anti-CTLA4) at different doses in advanced gastric cancer (17). The overall response rate was between 8% to 24% and the median OS between 4.8 to 6.9 months according to treatment arm. Others anti-PD1/anti-PD-L1/anti-CTLA4 mAbs are also currently under investigation in gastric cancer alone or in combination with chemotherapy. Nevertheless, up until now there is no published data concerning ICI plus chemotherapy in gastric cancer. The present randomized multicentric non-comparative phase II study aimed to assess the rate of patients alive and without progression at 4 months with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma, pre-treated with fluoropyrimidine + platinum +/- taxane, with two arms Folfiri plus durvalumab versus Folfiri plus durvalumab plus tremelimumab. Indeed, most patients in the French multicentric first-line GASTFOX trial (506 patients planned between 2017 and 2020) can be included in the second-line setting in the DURIGAST trial. Due to the lack of data concerning Folfiri plus durvalumab plus tremelimumab combination, a safety run-in phase will be performed at the beginning of the DURIGAST trial.

Detailed Description

      Gastric adenocarcinoma is the fourth most frequent cancer and the second leading cause of
      cancer mortality. Advanced gastric adenocarcinoma has a poor prognosis with short overall
      survival (ranging from 10% to 15% at 5-years) even after surgical complete resection and
      despite the progress in therapeutic approaches. Most of the patients have metastatic, locally
      advanced or recurrent unresectable disease. So, systemic treatment remains an important issue
      especially since chemotherapy improves survival and quality of life (compared to best
      supportive care alone). First-line chemotherapy depends on HER2 status, which also influenced
      overall survival (14 months for HER2 positive versus 10 months for HER2 negative tumors). In
      HER2 negative tumors standard first-line regimen is a doublet of fluoropyrimidine
      (5-fluorouracil or capecitabine) plus a platinum salt (cisplatin or oxaliplatin).
      5-fluorouracil (5-FU) and capecitabine as also cisplatin and oxaliplatin have similar
      efficacy but different toxicities.

      In patients whose tumor overexpresses the HER2 receptor adding trastuzumab to
      fluoropyrimidine/cisplatin regimen increased overall survival compared to chemotherapy alone.
      In HER2 negative tumors the addition of docetaxel to cisplatin/fluoropyrimidine regimen
      increased overall survival but its use remains limited in clinical practice because of its
      high toxicity. Preliminary results demonstrated a high efficacy with less toxicities of
      docetaxel-oxaliplatin-fluoropyrimidine combination, also called TFOX/FLOT regimen. Indeed, in
      France a large phase III trial comparing TFOX versus FOLFOX in first-line treatment of
      patients with advanced gastric or gastro-oesophageal junction adenocarcinoma is ongoing
      (GASTFOX, trial NCT03006432). Primary endpoint is progression-free survival (PFS) and 506
      patients are planned between 2017 and 2020 (actually at the date of January 30, 2018, 65
      patients are included).

      Second-line chemotherapy improves overall survival (OS) as compared to best supportive care
      alone in patients with an acceptable general condition (performance status 0-2). Indeed, with
      docetaxel monotherapy there was a significant difference in overall survival for the
      chemotherapy arm with a median of 5.2 versus 3.6 months in best supportive care alone arm
      (HR=0.67, p=0.01). Weekly paclitaxel monotherapy is also used because of its good
      efficacy-toxicity ratio. Irinotecan monotherapy also significantly improves overall survival
      compared to supportive care alone in a phase III study (4.0 versus 2.4 months; HR=0.48, 95%CI
      0.25-0.92; p=0.012). Recently ramucirumab monotherapy demonstrated its efficacy on overall
      survival in a randomized, placebo-controlled second-line metastatic study. In a randomized
      phase 3 trial ramucirumab also showed its efficacy in combination with paclitaxel versus
      paclitaxel monotherapy with a median overall survival of 9.6 versus 7.4 months, respectively
      (p=0.017; HR=0.81). However, the "amelioration du service medical rendu" (ASMR) assessed by
      the French "Haute Autorité de Santé" (HAS) consider an insufficient benefit to a
      reimbursement of ramucirumab in France. The HAS gave a moderate ASMR opinion (ASMR IV).

      Docetaxel is more and more frequently used in first-line chemotherapy then in this setting
      taxane (alone or combined with others drugs) cannot be used as second-line regimen. Indeed,
      based on a phase III trial FOLFIRI (5-FU plus irinotecan) is one most used regimen in
      second-line in European countries, especially in France. FFCD 0307 trial, a phase III
      comparing FOLFIRI-ECX (epirubicin-cisplatin-capecitabine) to the reverse sequence
      (ECX-FOLFIRI), showed that both sequences are possible.

      Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping
      immunosurveillance. For instance, interaction between PD1 (Program Death 1) and PD-L1
      (Program Death 1 ligand) will lead the activated T cell to a state of anergy. PD-L1 is up
      regulated on a wide range of cancers. Anti-PD1 and anti-PD-L1 monoclonal antibodies (mAbs),
      called immune checkpoint inhibitors (ICIs), have consequently been designed to restore T cell
      activity. Others ICIs are investigated, notably cytotoxic T-lymphocyte-associated protein 4
      (CTLA-4) inhibitors. CTLA-4 transmits an inhibitory signal to T cells to prevent early
      excessive T cell activation. CTLA4 blockade may stimulate a more robust antitumor response by
      sustaining activation and proliferation of T lymphocytes and may overcome immune suppression
      mediated by regulatory T cells. ICIs have been recently tested in many cancers with promising
      results, especially in tumors with microsatellite instability (MSI) and/or PD-L1
      overexpression.

      Preliminary results in metastatic gastric cancer with anti-PD1 mAbs are highly promising. In
      a trial with pembrolizumab, only PD-L1 positive tumors were eligible to the treatment with a
      cut off at 1%. Thirty-nine patients were enrolled and 67% had received at least two prior
      chemotherapy regimens. The overall response rate was 22%. The median PFS and OS were 1.9
      months and 11.4 months, respectively. KEYNOTE-059 Phase 2 multicohort study with
      pembrolizumab monotherapy in advanced gastric cancer treatment has been presented at ASCO
      2017 meeting. Among 259 patients included in the trial response rate was 11.6%. OS was 5.6
      months. Response rates were 15.5% in PDL1+ tumors versus 6.4% in PDL1- tumors and 57.1% in
      MSI tumors versus 9% in MSS tumors. Up until now, overlap between microsatellite instability
      and PD-L1 expression is unknown in gastric cancer. An anti-PD-L1 mAb (avelumab) was evaluated
      in a phase Ib expansion study (n=20, Japanese patients), with 15% of objective response rate
      and 11.9 weeks for progression-free survival. A second cohort with avelumab included 55
      patients for maintenance therapy after first-line chemotherapy, with 7.3% of objective
      response rate and 14 weeks of PFS. Phase I/II CheckMate-032 evaluated nivolumab (anti-PD-1) ±
      ipilimumab (anti-CTLA4) at different doses in advanced gastric cancer (17). The overall
      response rate was between 8% to 24% and the median OS between 4.8 to 6.9 months according to
      treatment arm.

      Others anti-PD1/anti-PD-L1/anti-CTLA4 mAbs are also currently under investigation in gastric
      cancer alone or in combination with chemotherapy. Nevertheless, up until now there is no
      published data concerning ICI plus chemotherapy in gastric cancer. Finally, immunogenic cell
      death induced by chemotherapy may enhance efficacy of ICIs. Durvalumab (MEDI4736) is a human
      monoclonal antibody directed against PD-L1 in development for the treatment of many cancers.
      A phase I study included 16 patients with advanced gastric cancer and the objective response
      rate was 25%. Tremelimumab is a fully human monoclonal antibody against CTLA-4. Durvalumab
      plus tremelimumab combination showed a manageable tolerability profile, with antitumour
      activity irrespective of PD-L1 status in non-small cell lung cancer (NSCLC). Durvalumab alone
      or combined with tremelimumab is evaluated in phase III studies in NSCLC (e.g NEPTUNE and
      MYSTIC), small cell lung cancer (CASPIAN), hepatocellular carcinoma (HIMALAYA), bladder
      cancer (DANUBE) and head and neck cancer (EAGLE and KESTREL).

      Concerning safety of anti-PD1 plus anti-CTLA4 combination, in the randomized phase I/II
      CheckMate-032 study, that included 160 patients, there was no unexpected toxicity signal.
      Grade 3 and 4 treatment-related adverse events were 17%, 47%, and 27%, respectively. These
      rates of grade 3 and 4 treatment-related adverse events are those usually found with the
      anti-PD1 plus anti-CTLA4 combination in other tumors, observed approximately in 40% of
      patients. Up until now, there is no published data concerning combination of ICIs plus
      irinotecan. Nevertheless, in all trial combining chemotherapy plus anti-PD1 and/or anti-CTLA4
      chemotherapy drugs were used at full-dose (5FU, oxaliplatin, cisplatin…). An Italian trial
      just started and combined full-dose FOLFOXIRI (5-FU 3200 mg/m2 plus irinotecan 165 mg/m2 and
      oxaliplatin 85 mg/m2) with bevacizumab (5 mg/kg) and atezolizumab (anti-PD-L1, 840 mg) in
      metastatic colorectal cancers as first-line treatment. FOLFOXIRI is a triplet chemotherapy
      more "toxic" than FOLFIRI doublet chemotherapy and this trial is a randomized phase II
      (FOLFOXIRI plus bevacizumab and atezolizumab versus FOLFOXIRI plus bevacizumab). There is,
      however, a preliminary safety phase in 6 patients, once they have all received at least 2
      cycles of treatment, the latter being administered at full dose (AtezoTRIBE trial,
      NCT03721653).

      The present randomized multicentric non-comparative phase II study aimed to assess the rate
      of patients alive and without progression at 4 months with advanced gastric or
      gastro-oesophageal junction (GEJ) adenocarcinoma, pre-treated with fluoropyrimidine +
      platinum +/- taxane, with two arms Folfiri plus durvalumab versus Folfiri plus durvalumab
      plus tremelimumab. Indeed, most patients in the French multicentric first-line GASTFOX trial
      (506 patients planned between 2017 and 2020) can be included in the second-line setting in
      the DURIGAST trial. Due to the lack of data concerning Folfiri plus durvalumab plus
      tremelimumab combination, a safety run-in phase will be performed at the beginning of the
      DURIGAST trial.
    

Trial Arms

NameTypeDescriptionInterventions
FOLFIRI plus durvalumabExperimentalDurvalumab: 1500 mg by 1-hour IV infusion. Every 4 weeks until progression FOLFIRI (1 course every 2 weeks, until progression): Irinotecan: 180 mg/m² by 2-hour IV infusion, Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) by 2-hours IV infusion, 5-FU bolus: 400 mg/m² by 10-minutes IV bolus, Continuous 5-FU: 2400 mg/m² by 46-hour IV infusion
  • Durvalumab
  • FOLFIRI Protocol
FOLFIRI plus durvalumab plus tremelimumabExperimentalDurvalumab: 1500 mg by 1-hour IV infusion - Every 4 weeks. Tremelimumab: 75 mg by 1-hour IV infusion - Every 4 weeks (for only 4 cycles). FOLFIRI (1 course every 2 weeks, until progression): Irinotecan: 180 mg/m² by 2-hour IV infusion Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) by 2-hours IV infusion 5-FU bolus: 400 mg/m² by 10-minutes IV bolus Continuous 5-FU: 2400 mg/m² by 46-hour IV infusion
  • Durvalumab
  • Tremelimumab
  • FOLFIRI Protocol

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years.

          -  Body weight > 30kg.

          -  Histologically proven advanced-stage unresectable adenocarcinoma of the stomach or the
             GEJ (Siewert II or III).

          -  Known MSS/MSI status or tumor tissue available (frozen or paraffin-embedded, primary
             tumors or metastases) in order to allow determination of MSS/MSI status. The
             investigator needs to ensure that tumor tissues will be sent after patient
             randomization.

          -  Failure to platinium-based 1st line therapy with or without trastuzumab, or early
             recurrent disease after surgery with neo-adjuvant and/or adjuvant platinium-based
             chemotherapy (within 6 months of the end of chemotherapy) or progression during
             neo-adjuvant and/or adjuvant platinium-based chemotherapy.

          -  Eligible for a second-line treatment with irinotecan and 5-FU.

          -  Measurable or non-measurable lesion according to the Response Evaluation Criteria in
             Solid Tumors (RECIST 1.1).

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          -  Adequate organ function: ANC ≥ 1.5 x 109/L, haemoglobin ≥ 9 g/dL, platelets ≥ 100 x
             109/L, AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastase(s)), GGT ≤ 3 x ULN (≤ 5
             x ULN in case of liver metastase(s)), bilirubin ≤ 1.5 x ULN, creatinin clearance > 40
             mL/min (MDRD).

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients.

          -  Man and woman who childbearing potential agrees to use two methods (one for the
             patient and one for the partner) of medically acceptable forms of contraception during
             the study and for 6 months after the last treatment intake.

          -  Patient is able to understand, sign, and date the written informed consent form at the
             screening visit prior to any protocol-specific procedures performed.

        Exclusion Criteria:

          -  - Concurrent enrolment in another clinical study - unless it is an observational study
             or during the follow-up period of an interventional study.

          -  Receipt of the last dose of anticancer therapy ≤ 2 weeks prior to the first dose of
             study drug.

          -  Radiotherapy within 4 weeks prior to the first dose of treatment.

          -  History of chronic inflammatory bowel disease (IBD).

          -  Current or prior bowel obstruction within 28 days before the first dose of study
             drugs.

          -  Any unresolved significant toxicity NCI CTCAE v4.0 ≥ grade 2 from previous anticancer
             therapy.

          -  Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable

          -  Major surgical procedure (e.g. exploratory laparoscopy is not considered as a major
             surgical procedure) within 28 days prior to the first dose of treatment.

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation.

          -  Active or prior documented autoimmune or inflammatory disorders (patients with
             alopecia, vitiligo, controlled hypo or hyperthyroidism, any chronic skin condition not
             requiring immunosuppressant therapy are eligible). Patients without active disease in
             the last 5 years may be included.

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring AEs or compromise the ability of the patient to give written
             informed consent.

          -  Severe cardiac disorders within 6 months.

          -  Severe liver dysfunction

          -  History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing
             pneumonia, or evidence of active pneumonitis on screening chest CT-scan.

          -  History of leptomeningeal carcinomatosis. Patients whose brain metastases have been
             treated may participate provided they show radiographic stability. In addition, any
             neurologic symptoms that developed either as a result of the brain metastases or their
             treatment must have resolved or be stable either, without the use of steroids, or are
             stable on a steroid dose of ≤10mg/day of prednisone or its equivalent for at least 14
             days prior to the start of treatment

          -  Positive test for HIV, active hepatitis B or hepatitis C, active tuberculosis.

          -  History of active primary immunodeficiency

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of study drugs (excepted: intranasal, inhaled, topical steroids or local steroid
             injection -at physiologic dose does not exceed 10 mg/day of prednisone or its
             equivalent - steroids as premedication for hypersensitivity reactions).

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of treatment

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients. In order to check all the contraindications of each drugs, please refer to
             the updated versions of the SmPCs presented in Appendix 9.

          -  Current or prior use of St. John's Wort within 14 days before the first dose of study
             drugs (St. John's Wort is not allowed during participation in the trial).

          -  Treatment with sorivudine or analogs (brivudine).

          -  Treatment with phenytoin or analogs.

          -  Prior treatment with irinotecan, anti-PD1, anti PD-L1, anti-CLTA4 or other
             immunotherapy for cancer treatment

          -  Known Uridine Diphosphate Glucuronyltransferase (UGT1A1) or Dihydropyrimidine
             Dehydrogenase (DPD) enzyme deficiencies.

          -  Active infection requiring intravenous antibiotics at the time of Day 1 of Cycle 1.

          -  Other malignancy within 5 years prior to study enrolment, except for localized cancer
             in situ, basal or squamous cell skin cancer.

          -  Pregnant or breastfeeding female patient.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients alive and without progression at 4 months
Time Frame:4 months
Safety Issue:
Description:Progression free survival (PFS) median is defined as the time between date of randomization and date of the first radiological progression (according to RECIST 1.1) or death (from any cause), whichever occurs first. Patients alive without progression will be censored at date of last news.

Secondary Outcome Measures

Measure:Percentage of patients alive and without progression at 4 months according to centralized review
Time Frame:4 months
Safety Issue:
Description:Progression free survival (PFS) median is defined as the time between date of randomization and date of the first radiological progression (according to RECIST 1.1) or death (from any cause), whichever occurs first. Patients alive without progression will be censored at date of last news.
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death (whatever the cause). Alive patients will be censured at date of last news.
Measure:Time to strategy failure
Time Frame:An average of 6 months
Safety Issue:
Description:Is defined as the time between randomization date and date of death (from any cause) or the date of first radiological progression in the FOLFIRI + durvalumab arm or date of the second radiological progression after re-introduction of tremelimumab in the FOLFIRI plus durvalumab plus tremelimumab arm or date of definitive discontinuation. In case a treatment is stopped for toxicity reason but re-introduced later for progression, then this progression will not be considered for this endpoint.
Measure:Adverse event frequency estimation according to NCI-CTCAE v4.0 classifications
Time Frame:An average of 6 months
Safety Issue:
Description:Toxicities will be graded according to the NCI-CTCAE v4.0 classifications.
Measure:Time to progression (TTP) (according to iRECIST)
Time Frame:An average of 1 year
Safety Issue:
Description:TTP : Time to progression (TTP): Is defined as the time between date of randomization and the date of first radiological progression (according to iRECIST). Patients without progression will be censored at date of last news or date of death. The death will not be considered as an event.
Measure:Progression-free survival (median PFS) (according to iRECIST)
Time Frame:An average of 1 year
Safety Issue:
Description:Progression free survival (PFS) median: Is defined as the time between date of randomization and date of the first radiological progression (according to iRECIST) or death (from any cause), whichever occurs first. Patients alive without progression will be censored at date of last news.
Measure:Best objective response rate (BRR) (according to iRECIST)
Time Frame:An average of 1 year
Safety Issue:
Description:Best Objective Response rate (BRR): Is defined as complete or partial response at the best response evaluation during the treatment according to iRECIST.
Measure:Disease control rate (DCR) (according to iRECIST)
Time Frame:An average of 1 year
Safety Issue:
Description:Disease control rate (DCR) at each timepoint: Is defined as complete or partial response or stable disease at the best response evaluation according to iRECIST.
Measure:Time to progression (TTP) (according to RECIST V1.1)
Time Frame:An average of 1 year
Safety Issue:
Description:TTP : Time to progression (TTP): Is defined as the time between date of randomization and the date of first radiological progression (according to RECIST v1.1). Patients without progression will be censored at date of last news or date of death. The death will not be considered as an event.
Measure:Progression-free survival (median PFS) (according to RECIST V1.1)
Time Frame:An average of 1 year
Safety Issue:
Description:Progression free survival (PFS) median: Is defined as the time between date of randomization and date of the first radiological progression (according to RECIST 1.1) or death (from any cause), whichever occurs first. Patients alive without progression will be censored at date of last news.
Measure:Best objective response rate (BRR) (according to RECIST V1.1)
Time Frame:An average of 1 year
Safety Issue:
Description:Best Objective Response rate (BRR): Is defined as complete or partial response at the best response evaluation during the treatment according to RECIST v1.1.
Measure:Disease control rate (DCR) (according to RECIST V1.1)
Time Frame:An average of 1 year
Safety Issue:
Description:Disease control rate (DCR) at each timepoint: Is defined as complete or partial response or stable disease at the best response evaluation according to RECIST v1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Federation Francophone de Cancerologie Digestive

Last Updated

October 14, 2020