Perioperative Treatment in Resectable Gastric Cancer with Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): A phase II study (GASPAR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Francois Baclesse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

6 Sep 2024 → 27 Nov 2025

Decision date (initial)

2024-09-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCa

External identifiers

EU CT number

2024-516299-13-00

EudraCT number

2020-004497-21

ClinicalTrials.gov

NCT04736485

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

To evaluate the pathologic response after pre-operative treatment

Secondary objectives 5

1. - To evaluate the impact of perioperative treatment on survival outcomes (disease-free and overall survival)
2. - To evaluate the histological R0 resection margin
3. - To establish the association between pCR and survival outcomes outcomes (disease-free and overall survival)
4. - To determine the safety profile of the combination Spartalizumab + FLOT regimen
5. - To evaluate the post-operative morbidity and mortality

Conditions and MedDRA coding

Resectable Gastric Cancer

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. - Age ≥ 18 years
2. - Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis)
3. - Histologically confirmed adenocarcinoma
4. - ECOG performance status score of 0 or 1
5. - Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block)
6. - All subjects must consent to allow the acquisition of blood samples for performance of correlative studies
7. - Screening laboratory values must meet the following criteria: o WBC ≥ 2000/ mm³ o Neutrophils ≥ 1500/ mm³ o Platelets ≥ 100 000/ mm³ o Hemoglobin ≥ 9.0 g/dL o Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN o Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula) o Potassium ≥ LLN o Magnesium ≥ LLN o Calcium ≥ LLN
8. - Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start
9. - 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
10. - Subject affiliated to a social security regimen
11. - Patient has signed informed consents obtained before any trial related activities and according to local guidelines

Exclusion criteria 25

1. - Subject with any distant metastasis
2. - Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion
3. - 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
4. - History of anterior organ transplant, including stem cell allograft
5. - Pneumonitis or interstitial lung disease
6. - History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
7. - Subject with active, known, or suspected autoimmune disease
8. - 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
9. - Known history of HIV or HBV infection
10. - Known active HCV infection
11. - Known history of active tuberculosis
12. - Vaccination with live vaccine within 30 days before the first dose of study treatment
13. - 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
14. - Recent or concomitant treatment with brivudine (herpes virostatic)
15. - Prior anticancer therapy for the current malignancy
16. - Known hypersensitivity to any of the study drugs or their excipients
17. - Chronic inflammable gastro-intestinal disease
18. - Uracilemia ≥ 16 ng/ml
19. - QT/QTc > 450 msec for men and > 470 msec for women
20. - Peripheral neuropathy ≥ Grade II
21. - Uncontrolled diabetes
22. - Active infection requiring systemic therapy
23. - Participation in another therapeutic clinical study
24. - Patient deprived of liberty or placed under the authority of a tutor
25. - Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of patients with pCR in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist

Secondary endpoints 8

1. - Disease-free survival (DFS) defined as time between inclusion and first progression according to RECIST v1.1 criteria or death whatever cause (in the absence of progression); patients without disease progression or death at the time of analysis will be censored at the time of the latest date of assessment
2. - Overall survival (OS) defined as the time between inclusion and death whatever cause; any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive
3. - 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
4. - Correlation between pCR and DFS
5. - Correlation between pCR and OS
6. - Toxicities of the combination Spartalizumab + FLOT regimen according to NCI CTCAE criteria v5.0
7. - Post-operative morbidity, defined post-operative complications grades II-V according to Clavien-Dindo classification during surgery, within 30 days after surgery or during the hospital stay
8. - Post-operative mortality, defined as the rate of patients died due to any cause during the 30 days post-surgery

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Francois Baclesse

Sponsor organisation

Centre Francois Baclesse

Address

3 Avenue Du General Harris, Cs 45026 Cs 45026

City

Caen Cedex 5

Postcode

14076

Country

France

Scientific contact point

Organisation

Centre Francois Baclesse

Contact name

LECONTE Alexandra

Public contact point

Organisation

Centre Francois Baclesse

Contact name

LECONTE Alexandra

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications