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

Gastric Cancer Clinical Trial

— SOCRATE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03760822
• Other study ID #: PRODIGE 55 - SOCRATE
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 16, 2018
• Est. completion date: September 2024

Study information

• Verified date: August 2023
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: September 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Stomach Cancer
• Stomach Neoplasm
• Stomach Neoplasms

Intervention

Drug:
• Ramucirumab
IV ramucirumab at 8 mg/kg on D1 and D15
• Paclitaxel
IV paclitaxel at 80 mg/m² on D1, D8 and D15

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive	Eli Lilly and Company

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient survival rate at 6 months	Rate of patients alive	at 6 months
Primary	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
Primary	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
Primary	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	Overall survival	Defined as time to death (whatever cause is) or for patients alive time to last news.	6 months
Secondary	Time to treatment failure	Time between randomization and disease progression, treatment interruption or death	6 months
Secondary	Progression-free survival	Progression-free survival (clinical and/or radiological) determined by the investigator based on RECIST V1.1	6 months