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Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT) (GASPAR)

Primary Purpose

Gastric Cancer by AJCC V8 Stage, Resectable Carcinoma

Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
perioperative treatment
Sponsored by
Centre Francois Baclesse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer by AJCC V8 Stage focused on measuring perioperative, spartalizumab, PDR001, Gastric Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis)
  • Histologically confirmed adenocarcinoma
  • ECOG performance status score of 0 or 1
  • Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block)
  • All subjects must consent to allow the acquisition of blood samples for performance of correlative studies

  • Screening laboratory values must meet the following criteria:

    • WBC ≥ 2000/ mm³
    • Neutrophils ≥ 1500/ mm³
    • Platelets ≥ 100 000/ mm³
    • Hemoglobin ≥ 9.0 g/dL
    • Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN
    • Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula)
    • Potassium ≥ LLN
    • Magnesium ≥ LLN
    • Calcium ≥ LLN
  • Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start
  • Subject in reproductive age must be willing to use adequate contraception during the study and at least 9 months in men and 12 months in women after the last dose of investigational drug. In addition, given the toxicities observed on the male reproductive system, a conservation of gametes will be proposed for men, as usually in routine practice
  • Subject affiliated to a social security regimen
  • Patient has signed informed consents obtained before any trial related activities and according to local guidelines

Exclusion Criteria:

Subject with any distant metastasis

  • Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion
  • Documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as NYHA III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis
  • History of anterior organ transplant, including stem cell allograft
  • Pneumonitis or interstitial lung disease
  • History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
  • Subject with active, known, or suspected autoimmune disease
  • Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment GASPAR Protocol - EUDRACT number: 2020-004497-21 - version 1.3 / 2021-01-18 Page 8 sur 44
  • Known history of HIV or HBV infection
  • Known active HCV infection
  • Known history of active tuberculosis
  • Vaccination with live vaccine within 30 days before the first dose of study treatment
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Recent or concomitant treatment with brivudine (herpes virostatic)
  • Prior anticancer therapy for the current malignancy
  • Known hypersensitivity to any of the study drugs or their excipients
  • Chronic inflammable gastro-intestinal disease
  • Uracilemia ≥ 16 ng/ml
  • QT/QTc > 450 msec for men and > 470 msec for women
  • Peripheral neuropathy ≥ Grade II
  • Uncontrolled diabetes
  • Active infection requiring systemic therapy
  • Participation in another therapeutic clinical study
  • Patient deprived of liberty or placed under the authority of a tutor
  • Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Sites / Locations

  • CHU Besançon
  • Centre François Baclesse
  • Centre Georges Francois Leclerc
  • Chru Lille
  • APHM Marseille
  • Institut Régional Cancer
  • APHP St Louis
  • Institut Mutualiste Montsouris
  • CHU Poitiers
  • CHU Robert Debré
  • Centre Eugène Marquis
  • ICO St Herblain
  • CH St Malo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FLOT regimen plus Spartalizumab

Arm Description

Standard FLOT regimen Docetaxel 50 mg/m² IV infusion on D1 Oxaliplatine 85 mg/m² IV infusion on D1 Leucovorin 200 mg/m² IV infusion on D1 Fluorouracile 2600 mg/m² 24 h IV infusion on D1 with Spartalizumab PDR001 Patients will received the fixed dose of 400 mg per IV infusion on D1 every four weeks (q4w) for 2 pre-operative cycles (8 weeks) and 2 post-operative cycles (8 weeks)

Outcomes

Primary Outcome Measures

Pathologic response after pre-operative treatment
Proportion of patients with pCR (pathologic complete response) in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist

Secondary Outcome Measures

Evaluate the impact of perioperative treatment on disease-free survival
Disease-free survival (DFS) defined as time between inclusion and first disease progression
Evaluate the impact of perioperative treatment on overall survival
Overall survival (OS) defined as the time between inclusion and death whatever cause;
The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival)
Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed
Treatment-Related Adverse Events
Type, grade and number of Adverse Events as Assessed by CTCAE v5.0

Full Information

First Posted
January 26, 2021
Last Updated
December 22, 2022
Sponsor
Centre Francois Baclesse
Collaborators
National Cancer Institute, France
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1. Study Identification

Unique Protocol Identification Number
NCT04736485
Brief Title
Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)
Acronym
GASPAR
Official Title
Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT): A Phase II Study (GASPAR)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 28, 2021 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Francois Baclesse
Collaborators
National Cancer Institute, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Multicenter, open-label, non randomized, phase 2 trial in resectable gastric or gastroesophageal junction adenocarcinoma: Perioperative Treatment by Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer by AJCC V8 Stage, Resectable Carcinoma
Keywords
perioperative, spartalizumab, PDR001, Gastric Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FLOT regimen plus Spartalizumab
Arm Type
Experimental
Arm Description
Standard FLOT regimen Docetaxel 50 mg/m² IV infusion on D1 Oxaliplatine 85 mg/m² IV infusion on D1 Leucovorin 200 mg/m² IV infusion on D1 Fluorouracile 2600 mg/m² 24 h IV infusion on D1 with Spartalizumab PDR001 Patients will received the fixed dose of 400 mg per IV infusion on D1 every four weeks (q4w) for 2 pre-operative cycles (8 weeks) and 2 post-operative cycles (8 weeks)
Intervention Type
Drug
Intervention Name(s)
perioperative treatment
Intervention Description
FLOT + Spartalizumab
Primary Outcome Measure Information:
Title
Pathologic response after pre-operative treatment
Description
Proportion of patients with pCR (pathologic complete response) in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist
Time Frame
At surgery, an average 3 months after treatment initiation
Secondary Outcome Measure Information:
Title
Evaluate the impact of perioperative treatment on disease-free survival
Description
Disease-free survival (DFS) defined as time between inclusion and first disease progression
Time Frame
Through study completion, an average of 5 follow-up year
Title
Evaluate the impact of perioperative treatment on overall survival
Description
Overall survival (OS) defined as the time between inclusion and death whatever cause;
Time Frame
Up to death
Title
The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival)
Description
Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed
Time Frame
At surgery, an average 3 months after treatment initiation
Title
Treatment-Related Adverse Events
Description
Type, grade and number of Adverse Events as Assessed by CTCAE v5.0
Time Frame
Toxicities occurring up to 1 month after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis) Histologically confirmed adenocarcinoma ECOG performance status score of 0 or 1 Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block) All subjects must consent to allow the acquisition of blood samples for performance of correlative studies Screening laboratory values must meet the following criteria: WBC ≥ 2000/ mm³ Neutrophils ≥ 1500/ mm³ Platelets ≥ 100 000/ mm³ Hemoglobin ≥ 9.0 g/dL Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula) Potassium ≥ LLN Magnesium ≥ LLN Calcium ≥ LLN Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start Subject in reproductive age must be willing to use adequate contraception during the study and at least 9 months in men and 12 months in women after the last dose of investigational drug. In addition, given the toxicities observed on the male reproductive system, a conservation of gametes will be proposed for men, as usually in routine practice Subject affiliated to a social security regimen Patient has signed informed consents obtained before any trial related activities and according to local guidelines Exclusion Criteria: Subject with any distant metastasis Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion Documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as NYHA III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis History of anterior organ transplant, including stem cell allograft Pneumonitis or interstitial lung disease History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma) Subject with active, known, or suspected autoimmune disease Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment GASPAR Protocol - EUDRACT number: 2020-004497-21 - version 1.3 / 2021-01-18 Page 8 sur 44 Known history of HIV or HBV infection Known active HCV infection Known history of active tuberculosis Vaccination with live vaccine within 30 days before the first dose of study treatment Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Recent or concomitant treatment with brivudine (herpes virostatic) Prior anticancer therapy for the current malignancy Known hypersensitivity to any of the study drugs or their excipients Chronic inflammable gastro-intestinal disease Uracilemia ≥ 16 ng/ml QT/QTc > 450 msec for men and > 470 msec for women Peripheral neuropathy ≥ Grade II Uncontrolled diabetes Active infection requiring systemic therapy Participation in another therapeutic clinical study Patient deprived of liberty or placed under the authority of a tutor Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Facility Information:
Facility Name
CHU Besançon
City
Besançon
Country
France
Facility Name
Centre François Baclesse
City
Caen
Country
France
Facility Name
Centre Georges Francois Leclerc
City
Dijon
Country
France
Facility Name
Chru Lille
City
Lille
Country
France
Facility Name
APHM Marseille
City
Marseille
Country
France
Facility Name
Institut Régional Cancer
City
Montpellier
Country
France
Facility Name
APHP St Louis
City
Paris
Country
France
Facility Name
Institut Mutualiste Montsouris
City
Paris
Country
France
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Facility Name
CHU Robert Debré
City
Reims
Country
France
Facility Name
Centre Eugène Marquis
City
Rennes
Country
France
Facility Name
ICO St Herblain
City
Saint-Herblain
Country
France
Facility Name
CH St Malo
City
Saint-Malo
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35549674
Citation
Dos Santos M, Lequesne J, Leconte A, Corbinais S, Parzy A, Guilloit JM, Varatharajah S, Brachet PE, Dorbeau M, Vaur D, Weiswald LB, Poulain L, Le Gallic C, Castera-Tellier M, Galais MP, Clarisse B. Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR). BMC Cancer. 2022 May 12;22(1):537. doi: 10.1186/s12885-022-09623-z.
Results Reference
derived

Learn more about this trial

Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)

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