Second-Line Chemotherapy With Ramucirumab +/- Paclitaxel in Elderly Advanced Gastric or Gastroesophageal Junction Cancer Patients (SOCRATE)

The primary objective is to evaluate six months survival rate and quality of life at 4 months of ramucirumab alone or in combination with paclitaxel in patients aged 70 years or more who have stomach or GEJ adenocarcinoma and whose first line of fluoropyrimidine- and platinumcontaining treatment has failed.

The co-primary endpoints are the following:

• Six months survival rate
• Quality of life at 4 months as assessed by the following three target dimensions of the EORTC QLQ-ELD14 questionnaire: mobility, illness burden and worries about the future

Study Overview

• Status: Active, not recruiting
• Conditions: Stomach Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; Stomach Neoplasm
• Intervention / Treatment: Drug: Ramucirumab; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Flore GEILLON; Phone Number: +33 3 80 39 34 83; Email: flore.geillon@u-bourgogne.fr
• Study Contact Backup: Name: Marie MOREAU; Phone Number: +33 3 80 39 34 04; Email: marie.moreau@u-bourgogne.fr

Study Locations

• France
  • Abbeville, France
    • CH -
  • Albi, France
    • CH - Albi
  • Amiens, France
    • PRIVEE - L'Europe
  • Angers, France
    • CAC - ICO Site Paul Papin
  • Antony, France
    • Privee - Hopital Prive
  • Argenteuil, France
    • Ch - Victor Dupouy
  • Ars-Laquenexy, France
    • Ch - Metz Thionville Mercy
  • Auxerre, France
    • Ch - Ght Unyon Auxerre
  • Avignon, France
    • Privee - Institut Du Cancer Avignon Provence
  • Bayonne, France
    • CH - Côte Basque
  • Beauvais, France
    • Ch - Beauvais Ch
  • Besançon, France
    • Chu - Jean Minjoz
  • Bordeaux, France
    • Privee - Tivoli
  • Boujan-sur-Libron, France
    • PRIVEE - Polyclinique Saint Privat
  • Boulogne-sur-Mer, France
    • Ch - Duchenne
  • Bourgoin-Jallieu, France
    • Ch - Pierre Oudot
  • Brest, France
    • Privee - Pasteur Lanroze
  • Caen, France
    • Chu - Côte de Nacre
  • Caen, France
    • Cac - François Baclesse
  • Cahors, France
    • Ch - Jean Rougier
  • Caluire-et-Cuire, France
    • Privee - Infirmerie Protestante
  • Carcassonne, France
    • CH -
  • Castres, France
    • Ch - Castres Mazamet Chi
  • Challes-les-Eaux, France
    • Privé - Médipole de Savoie
  • Chalon-sur-Saône, France
    • Prive - Sainte Marie
  • Cholet, France
    • CH -
  • Colmar, France
    • Hôpitaux Civils de Colmar
  • Colmar, France
    • Ch - Hôpitaux Civils de Colmar
  • Colombes, France
    • Chu - Louis Mourier
  • Compiègne, France
    • Prive - Saint Côme
  • Cornebarrieu, France
    • Prive - Cédres
  • Créteil, France
    • CHU - Henri Mondor
  • Dechy, France
    • Prive - Centre Leonard de Vinci
  • Dijon, France
    • Cac - Gf Leclerc
  • Dijon, France
    • Chu - Francois Mitterrand
  • Dunkerque, France
    • CH -
  • Elbeuf, France
    • CHI - Elbeuf Louviers Val de Reuil
  • Plérin, France
    • Clinique privée - CENTRE CARIO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed, unresectable, locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, whatever HER2 status
• Aged ≥ 70 years
• WHO < 2
• Estimated life expectancy > 3 months
• Measurable or non-measurable disease according to RECIST 1.1 criteria
• Documented progression during first-line fluoropyrimidine- and platinum- or irinotecan containing chemotherapy (with or without anthracycline), or during the 4 months following the last cycle of such chemotherapy administered for metastatic or locally advanced disease, or during the 6 months following the last dose of adjuvant therapy containing fluoropyrimidine and platinium (treatment by immunotherapy is allowed)

• Adequate hepatic, renal and hematologic function:

  • ANC ≥ 1 500 / mm3, platelets ≥ 100 000 / mm3, hemoglobin ≥ 9 g/dL
  • Blood creatinine ≤ 1.5 x ULN and creatinine clearance (MDRD formula) ≥ 40 mL/min
  • Total bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN (≤ 5 x ULN if hepatic metastasis)
  • INR ≤ 1.5 or INR ≤ 3 for patients taking AVK and PTT ≤ 5 seconds above the ULN
  • Dipstick proteinuria ≤ 1+ or 24 hour proteinuria < 1 g in total
• EORTC QLQ-C30 + QLQ-ELD14, completed and faxed to the Randomization, Management and Analysis Center of the FFCD
• IADL geriatric questionnaire, completed and faxed to Randomization Management and Analysis Center of FFCD
• Signed informed consent

Exclusion Criteria:

• Known cerebral metastasis
• Prior treatment by taxanes
• Prior treatment with an antiangiogenic
• Neuropathy of grade ≥ 2 (NCI-CTCAE 4.0)
• Unresolved partial or total bowel obstruction, inflammatory bowel disease (such as Crohn's disease or ulcerative colitis) or extensive gastrointestinal (GI) resection combined with chronic diarrhea
• GI perforation and/or fistulae in the 6 months preceding randomization.
• GI bleeding within the last 3 months of grade ≥ 3 (NCI-CTCAE 4.0)
• Chronic use of antiplatelet drugs (including aspirin, but a daily intake of ≤ 325 mg/day is accepted), non-steroidal anti-inflammatory drugs (ibuprofen, naproxen), dipyridamole, clopidogrel or similar agents
• Any arterial thromboembolic event (such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack) in the 6 months preceding randomization
• A life-threatening episode of pulmonary embolism in the 6 months preceding randomization
• Deep-vein thrombosis, pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant" during the 3 months prior to first dose of protocol therapy
• Uncompensated congestive heart failure or uncontrolled arrhythmia
• Uncontrolled hypertension (≥ 140/90 mm Hg for > 4 weeks) despite properly observed antihypertensive therapy
• Cirrhosis at a level of Chilg-Pugh B or C; or cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Serious or unhealed wound, peptic ulcer or fracture within 28 days of randomization
• Radiotherapy or major surgery within 28 days of prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior the first dose of protocol therapy
• Known allergy to paclitaxel or ramucirumab
• Another concomitant cancer or a history of cancer in the last 5 years, except cervical carcinoma in situ, cutaneous basal-cell or squamous-cell carcinoma, or any other carcinoma in situ deemed to be successfully treated
• Lack of effective contraception in patients (man and/or women) of childbearing age, and/or their
• Persons deprived of liberty or under supervision
• Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramucirumab; IV ramucirumab at 8 mg/kg on D1 and D15	Drug: Ramucirumab; IV ramucirumab at 8 mg/kg on D1 and D15; Other Names: Cyramza
Active Comparator: Ramucirumab + Paclitaxel; IV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15	Drug: Ramucirumab; IV ramucirumab at 8 mg/kg on D1 and D15; Other Names: Cyramza; Drug: Paclitaxel; IV paclitaxel at 80 mg/m² on D1, D8 and D15; Other Names: Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient survival rate at 6 months	Rate of patients alive	at 6 months
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: mobility	Derived from items 31,33 and 34of the ELD14 questionnaire. The score is from 0 to 100. The endpoint is defined as the difference of at least 10 points (clinical significance) between baseline score and 4-months score.	at 4 months
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the future	Derived from items 31,33 and 34of the ELD14 questionnaire. The score is from 0 to 100. The endpoint is defined as the difference of at least 10 points (clinical significance) between baseline score and 4-months score.	at 4 months
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: illness burden	Derived from items 43 and 44of the ELD14 questionnaire. The score is from 0 to 100. The endpoint is defined as the difference of at least 10 points (clinical significance) between baseline score and 4-months score	at 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as time to death (whatever cause is) or for patients alive time to last news.	6 months
Time to treatment failure	Time between randomization and disease progression, treatment interruption or death	6 months
Progression-free survival	Progression-free survival (clinical and/or radiological) determined by the investigator based on RECIST V1.1	6 months

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Astrid Lièvre, Pr, CHU de Pontchaillou - Rennes

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: second line therapy; elderly patient; ramucirumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Ramucirumab
• Other Study ID Numbers: PRODIGE 55 - SOCRATE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No