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

Phase 2
Active, not recruiting
Conditions
Stomach Neoplasm
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Stomach Cancer
Interventions
Registration Number
NCT03760822
Lead Sponsor
Federation Francophone de Cancerologie Digestive
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

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
112
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
RamucirumabRamucirumabIV ramucirumab at 8 mg/kg on D1 and D15
Ramucirumab + PaclitaxelRamucirumabIV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15
Ramucirumab + PaclitaxelPaclitaxelIV ramucirumab at 8 mg/kg on D1 and D15 IV paclitaxel at 80 mg/m² on D1, D8 and D15
Primary Outcome Measures
NameTimeMethod
Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the futureat 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 burdenat 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 monthsat 6 months

Rate of patients alive

Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: mobilityat 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 Outcome Measures
NameTimeMethod
Time to treatment failure6 months

Time between randomization and disease progression, treatment interruption or death

Progression-free survival6 months

Progression-free survival (clinical and/or radiological) determined by the investigator based on RECIST V1.1

Overall survival6 months

Defined as time to death (whatever cause is) or for patients alive time to last news.

Trial Locations

Locations (35)

CH - Albi

🇫🇷

Albi, France

Privee - Hopital Prive

🇫🇷

Antony, France

CH -

🇫🇷

Dunkerque, France

Ch - Jean Rougier

🇫🇷

Cahors, France

Ch - Metz Thionville Mercy

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Ars-Laquenexy, France

Ch - Ght Unyon Auxerre

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Auxerre, France

PRIVEE - L'Europe

🇫🇷

Amiens, France

CAC - ICO Site Paul Papin

🇫🇷

Angers, France

Ch - Victor Dupouy

🇫🇷

Argenteuil, France

Privee - Institut Du Cancer Avignon Provence

🇫🇷

Avignon, France

Ch - Cote Basque

🇫🇷

Bayonne, France

Ch - Beauvais Ch

🇫🇷

Beauvais, France

Privee - Tivoli

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Bordeaux, France

Chu - Jean Minjoz

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Besançon, France

PRIVEE - Polyclinique Saint Privat

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Boujan-sur-Libron, France

Ch - Duchenne

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Boulogne-sur-Mer, France

Ch - Pierre Oudot

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Bourgoin-Jallieu, France

Ch - Hopitaux Civils de Colmar

🇫🇷

Colmar, France

Prive - Saint Côme

🇫🇷

Compiègne, France

Chu - Côte de Nacre

🇫🇷

Caen, France

Privee - Pasteur Lanroze

🇫🇷

Brest, France

Cac - François Baclesse

🇫🇷

Caen, France

Privee - Infirmerie Protestante

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Caluire-et-Cuire, France

Chu - Henri Mondor

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Créteil, France

Prive - Médipole de Savoie

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Challes-les-Eaux, France

Ch - Castres Mazamet Chi

🇫🇷

Castres, France

Prive - Sainte Marie

🇫🇷

Chalon-sur-Saône, France

Hopitaux civils de Colmar

🇫🇷

Colmar, France

Prive - Cédres

🇫🇷

Cornebarrieu, France

Chu - Louis Mourier

🇫🇷

Colombes, France

Chu - Francois Mitterrand

🇫🇷

Dijon, France

Prive - Centre Leonard de Vinci

🇫🇷

Dechy, France

Cac - Gf Leclerc

🇫🇷

Dijon, France

Clinique privée - CENTRE CARIO

🇫🇷

Plérin, France

CHI - Elbeuf Louviers Val de Reuil

🇫🇷

Elbeuf, France

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