LOGICAN: Oxaliplatin in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer

Sponsor

UNICANCER (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05476796

Collaborator

Servier (Industry)

118

Enrollment

Locations

Arms

59.2

Anticipated Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Oxaliplatin in combination with trifluridine/tipiracil or 5-fluorouracile (5-FU) in frail patients with advanced, recurrent or metastatic gastric, oesophageal or gastroesophageal junction cancer.

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma Esophagus Adenocarcinoma Gastroesophageal Junction Adenocarcinoma	Drug: Trifluridine/Tipiracil Drug: Oxaliplatin Drug: FOLFOX regimen	Phase 2

Detailed Description

Randomized, open label, comparative, multicentric, phase II trial comparing trifluridine/tipiracil + oxaliplatin vs FOLFOX regimen as first-line palliative therapy in frail patients with advanced, recurrent or metastatic gastric, oesophageal or gastroesophageal junction cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

118 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Phase II Study Evaluating Trifluridine/Tipiracil Plus Oxaliplatin Versus FOLFOX in Patients With Gastric, Oesophagus or Gastroesophageal Junction Adenocarcinoma Locally Advanced, Recurrent or Metastatic, Ineligible for Triplet Chemotherapy

Anticipated Study Start Date :

Oct 24, 2022

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trifluridine/Tipiracil + Oxaliplatin Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² twice-daily [BID] for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity. Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity.	Drug: Trifluridine/Tipiracil Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² BID for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity. Other Names: Lonsurf Drug: Oxaliplatin Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity.
Active Comparator: FOLFOX Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity.	Drug: FOLFOX regimen Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity.

Arm

Intervention/Treatment

Experimental: Trifluridine/Tipiracil + Oxaliplatin

Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² twice-daily [BID] for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity. Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity.

Drug: Trifluridine/Tipiracil

Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² BID for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity.

Other Names:

Lonsurf

Drug: Oxaliplatin

Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity.

Active Comparator: FOLFOX

Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity.

Drug: FOLFOX regimen

Outcome Measures

Primary Outcome Measures

Progression free-survival [From randomization to disease progression or death up to 5 years]
The progression-free survival (PFS) is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Secondary Outcome Measures

Objective response rate [5 years]
Objective response rate (ORR) is defined as the percentage of patients with a best response during treatment being either Complete Response (CR) or Partial Response (PR).
Overall survival [From randomization to death from any cause, up to 5 years]
The overall survival (OS) is the length of time from randomization that patients enrolled in the study are still alive.
Incidence of Treatment Adverse Events [Throughout study completion, up to 5 years]
The tolerance and safety will be evaluated by toxicity (acute [<1 months after the end of the trial treatment] and late [≥1 month after the end of the trial treatment), assessed using the Common terminology criteria for adverse events version 5.0 (CTCAE v5.0). CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
Time to patient performance status deterioration >2 [From randomization to PS deterioration >2, up to 5 years]
Time to performance status (PS) deterioration >2 is defined as the time between patient randomisation and the first date when PS>2. The Eastern Cooperative Oncology Group (ECOG) PS, a simple measure of functional status, determines ability of patient to tolerate therapies. It has scores ranging from 0 to 5 (0 = "fully active", 1 = "completely ambulatory", 2 = "<50% in bed during the day", 3 = ">50% in bed, but not bedbound", 4 = "bedbound", and 5 = "death").
Quality of life questionnaire - Core 30 (QLQ-C30) [From baseline until disease progression, up to 1 year]
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of the stomach, oesophagus or gastroesophageal junction (GEJ).
No dysphagia or difficulty in swallowing.
No overexpression/amplification of HER2 (IHC 0 or 1+; if IHC is 2+, HIS must be negative). Known combined positive scor (CPS) PD-L1 score (result in % with the name of the method used). The microsatellite and mismatch repair (MMR) status of patient's tumour (MSI/MSS and pMMR/dMMR) must also be known at the time of screening (IHC and PCR tests have to be done).
At least one evaluable lesion according to RECIST v1.1 outside any previously irradiated area.
No prior palliative chemotherapy.
Age ≥18 years old.
Patient unfit for triplet chemotherapy, defined with ONE of the following criteria:

ECOG-PS=2
Age ≥70 year old PLUS one frailty criteria on Activities of Daily Living (ADL)/Instrumental Activities of Daily Living (IADL) score
Denutrition (defined by albumin <30 g/L)
Other criterion left at investigator's discretion (this later must be filled in by the investigator).

Adequate organs function:

Absolute neutrophils count ≥1.5x10⁹/L
Platelets count ≥100x10⁹/L
Haemoglobin ≥9 g/L
Serum bilirubin levels <2 times upper limit of normal (ULN), up to 2.5 times ULN in case of hepatic metastasis (biliary drainage allowed)
Transaminases <5 times ULN
Creatinine clearance >40 mL/min

No Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia <16 ng/ml)
Women of childbearing potential must have a negative serum or urine pregnancy test done within 14 days before the first study treatment.
Patients must agree to use adequate contraception methods for the duration of study treatment and within 6 months after completing treatment.
Patients must be affiliated to a Social Security System (or equivalent).
Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
Availability of archived tumour material for ancillary studies

Exclusion Criteria:

Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin treated by surgery).
Adjuvant chemotherapy or radio-chemotherapy completed for less than 6 months.
Peripheral neuropathy of NCI-CTCAE grade ≥2 at baseline.
Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients.
Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
Previous treatment with trifluridine/tipiracil.
Known Human Immunodeficiency Virus (HIV) infection.
Active Hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV).
Interstitial lung disease.
Prior pneumonitis requiring systemic corticosteroid therapy.
Active infections.
Pregnant or breastfeeding woman.
Participation in another therapeutic trial within the 30 days prior to randomisation.
Persons deprived of their liberty or under protective custody or guardianship.
Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia (for men: QTc ≥450 msec, for women: QTc ≥470 msec)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Clinique de l'Europe	Amiens	France	80000
2	Hopital Privé Arras Les Bonnettes	Arras	France	62000
3	Institut Sainte Catherine	Avignon	France	84000
4	Centre Hospitalier de Beauvais	Beauvais	France	60021
5	CHU Besançon - Hôpital Jean Minjoz	Besançon	France	25030
6	CHU Morvan	Brest	France	29200
7	Centre Jean Perrin	Clermont-Ferrand	France	63011
8	Centre Georges François Leclerc	Dijon	France	21079
9	Hôpital Nord-Ouest Villefranche-sur-Saône	Gleizé	France	69400
10	Centre Léon Bérard	Lyon	France	69373
11	Hôpital Saint Joseph	Marseille	France	13008
12	Hôpital Nord Franche Comté	Montbéliard	France	25250
13	Centre Antoine Lacassagne	Nice	France	06189
14	Hôpital Saint Louis	Paris	France	75010
15	Hopital Europeen Georges Pompidou	Paris	France	75015
16	CHU de Poitiers	Poitiers	France	86000
17	CHU - Hôpital Robert Debré	Reims	France	51092
18	Institut Jean Godinot	Reims	France	51100
19	CHU Rouen - Charles Nicolle	Rouen	France	76000
20	Institut de cancérologie Strasbourg Europe	Strasbourg	France	67033
21	CHU Nancy - Hôpital Brabois	Vandœuvre-lès-Nancy	France	54500