Clinical trial NCT03760822: Second-Line Chemotherapy With Ramucirumab +/- Paclitaxel in Elderly Advanced Gastric or Gastroesophageal Junction Cancer Patients
Official title: Second-Line Chemotherapy With Ramucirumab +/- Paclitaxel in Elderly Advanced Gastric or Gastroesophageal Junction Cancer Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stomach Cancer
Stomach Neoplasm
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Keywords: ramucirumab
elderly patient
second line therapy
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2018-11-30
Enrollment: 112
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Patient survival rate at 6 months
timeFrame: at 6 months
measure: Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: mobility
timeFrame: at 4 months
measure: Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: worries about the future
timeFrame: at 4 months
measure: Quality of life at 4 months as assessed by the following dimension of the EORTC QLQ-ELD14 questionnaire: illness burden
timeFrame: at 4 months
Secondary outcomes:
measure: Overall survival
timeFrame: 6 months
measure: Time to treatment failure
timeFrame: 6 months
measure: Progression-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Abbeville
country: France
facility: CH -
city: Albi
country: France
facility: CH - Albi
city: Amiens
country: France
facility: PRIVEE - L'Europe
city: Angers
country: France
facility: CAC - ICO Site Paul Papin
city: Antony
country: France
facility: Privee - Hopital Prive
city: Argenteuil
country: France
facility: Ch - Victor Dupouy
city: Ars-Laquenexy
country: France
facility: Ch - Metz Thionville Mercy
city: Auxerre
country: France
facility: Ch - Ght Unyon Auxerre
city: Avignon
country: France
facility: Privee - Institut Du Cancer Avignon Provence
city: Bayonne
country: France
facility: Ch - Cote Basque
city: Beauvais
country: France
facility: Ch - Beauvais Ch
city: Besançon
country: France
facility: Chu - Jean Minjoz
city: Bordeaux
country: France
facility: Privee - Tivoli
city: Boujan-sur-Libron
country: France
facility: PRIVEE - Polyclinique Saint Privat
city: Boulogne-sur-Mer
country: France
facility: Ch - Duchenne
city: Bourgoin-Jallieu
country: France
facility: Ch - Pierre Oudot
city: Brest
country: France
facility: Privee - Pasteur Lanroze
city: Caen
country: France
facility: Cac - François Baclesse
city: Caen
country: France
facility: Chu - Côte de Nacre
city: Cahors
country: France
facility: Ch - Jean Rougier
city: Caluire-et-Cuire
country: France
facility: Privee - Infirmerie Protestante
city: Carcassonne
country: France
facility: CH -
city: Castres
country: France
facility: Ch - Castres Mazamet Chi
city: Challes-les-Eaux
country: France
facility: Prive - Médipole de Savoie
city: Chalon-sur-Saône
country: France
facility: Prive - Sainte Marie
city: Cholet
country: France
facility: CH -
city: Colmar
country: France
facility: Ch - Hopitaux Civils de Colmar
city: Colmar
country: France
facility: Hopitaux civils de Colmar
city: Colombes
country: France
facility: Chu - Louis Mourier
city: Compiègne
country: France
facility: Prive - Saint Côme
city: Cornebarrieu
country: France
facility: Prive - Cédres
city: Créteil
country: France
facility: Chu - Henri Mondor
city: Dechy
country: France
facility: Prive - Centre Leonard de Vinci
city: Dijon
country: France
facility: Cac - Gf Leclerc
city: Dijon
country: France
facility: Chu - Francois Mitterrand
city: Dunkerque
country: France
facility: CH -
city: Elbeuf
country: France
facility: CHI - Elbeuf Louviers Val de Reuil
city: Plérin
country: France
facility: Clinique privée - CENTRE CARIO
Study officials:
affiliation: CHU de Pontchaillou - Rennes
name: Astrid Lièvre, Pr
role: PRINCIPAL_INVESTIGATOR
References: