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

Federation Francophone de Cancerologie Digestive

Status and phase: Active, not recruiting; Phase 2

Conditions: Gastric Cancer; Stomach Neoplasm; Gastroesophageal Junction Adenocarcinoma; Stomach Cancer

Treatments: Drug: Paclitaxel; Drug: Ramucirumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03760822

PRODIGE 55 - SOCRATE

Details and patient eligibility

About

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

Enrollment: 112 patients

Sex: All

Ages: 70+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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112 participants in 2 patient groups

Ramucirumab

Experimental group

Description:

IV ramucirumab at 8 mg/kg on D1 and D15

Treatment:

Drug: Ramucirumab

Ramucirumab + Paclitaxel

Active Comparator group

Description:

IV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15

Treatment:

Drug: Ramucirumab

Drug: Paclitaxel