Second-Line Chemotherapy With Ramucirumab +/- Paclitaxel in Elderly Advanced Gastric or Gastroesophageal Junction Cancer Patients
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 112
- Locations
- 35
- Primary Endpoint
- Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the future
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed, unresectable, locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, whatever HER2 status
- •Aged ≥ 70 years
- •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
Arms & Interventions
Ramucirumab
IV ramucirumab at 8 mg/kg on D1 and D15
Intervention: Ramucirumab (Drug)
Ramucirumab + Paclitaxel
IV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15
Intervention: Ramucirumab (Drug)
Ramucirumab + Paclitaxel
IV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15
Intervention: Paclitaxel (Drug)
Outcomes
Primary Outcomes
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the future
Time Frame: 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
Time Frame: 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
Patient survival rate at 6 months
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- Time to treatment failure(6 months)
- Progression-free survival(6 months)
- Overall survival(6 months)