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

Study Overview
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Brief Summary
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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

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

Conditions
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Stomach Cancer, Stomach Neoplasm, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ramucirumab, elderly patient, second line therapy