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

Sponsor

Federation Francophone de Cancerologie Digestive (Other)

Overall Status

Recruiting

CT.gov ID

NCT03760822

Collaborator

Eli Lilly and Company (Industry)

112

Enrollment

Locations

Arms

57.5

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Stomach Cancer Stomach Neoplasm Gastric Cancer Gastroesophageal Junction Adenocarcinoma	Drug: Ramucirumab Drug: Paclitaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 16, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Patient survival rate at 6 months [at 6 months]
Rate of patients alive
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: mobility [at 4 months]
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.
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the future [at 4 months]
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.
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: illness burden [at 4 months]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	CH -	Abbeville	France
2	CH - Albi	Albi	France
3	PRIVEE - L'Europe	Amiens	France
4	CAC - ICO Site Paul Papin	Angers	France
5	Privee - Hopital Prive	Antony	France
6	Ch - Victor Dupouy	Argenteuil	France
7	Ch - Metz Thionville Mercy	Ars-Laquenexy	France
8	Ch - Ght Unyon Auxerre	Auxerre	France
9	Privee - Institut Du Cancer Avignon Provence	Avignon	France
10	Ch - Cote Basque	Bayonne	France
11	Ch - Beauvais Ch	Beauvais	France
12	Chu - Jean Minjoz	Besançon	France
13	Privee - Tivoli	Bordeaux	France
14	PRIVEE - Polyclinique Saint Privat	Boujan-sur-Libron	France
15	Ch - Duchenne	Boulogne-sur-Mer	France
16	Ch - Pierre Oudot	Bourgoin-Jallieu	France
17	Privee - Pasteur Lanroze	Brest	France
18	Cac - François Baclesse	Caen	France
19	Chu - Côte de Nacre	Caen	France
20	Ch - Jean Rougier	Cahors	France
21	Privee - Infirmerie Protestante	Caluire-et-Cuire	France
22	CH -	Carcassonne	France
23	Ch - Castres Mazamet Chi	Castres	France
24	Prive - Médipole de Savoie	Challes-les-Eaux	France
25	Prive - Sainte Marie	Chalon-sur-Saône	France
26	CH -	Cholet	France
27	Ch - Hopitaux Civils de Colmar	Colmar	France
28	Hopitaux civils de Colmar	Colmar	France
29	Chu - Louis Mourier	Colombes	France
30	Prive - Saint Côme	Compiègne	France
31	Prive - Cédres	Cornebarrieu	France
32	Chu - Henri Mondor	Créteil	France
33	Prive - Centre Leonard de Vinci	Dechy	France
34	Cac - Gf Leclerc	Dijon	France
35	Chu - Francois Mitterrand	Dijon	France
36	CH -	Dunkerque	France
37	CHI - Elbeuf Louviers Val de Reuil	Elbeuf	France
38	Clinique privée - CENTRE CARIO	Plérin	France