Assessment of Ramucirumab Plus Paclitaxel as Switch MANteInance Versus Continuation of First-line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers

NCT02934464 | Unknown Phase 3

• 1 other identifier: INT 103-16
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, multicenter phase III trial of ramucirumab plus paclitaxel, given as switch maintenance, versus continuation of first-line chemotherapy, given as per standard clinical practice, in subjects with unresectable locally advanced or metastatic HER-2 negative gastric or GEJ cancer, without disease progression following 3 months of first-line doublet chemotherapy. The acceptable first-line or lead-in chemotherapy will be:

• FOLFOX4:Oxaliplatin 85 mg/m2. l-Leucovorin 100 mg/m2 5-fluorouracil 400/600 mg/m2. Cycle length is 2 weeks +/- 3 days.
• ModifiedFOLFOX6: Oxaliplatin a 85 mg/m2. l-Leucovorin 200 mg/m2. 5-fluorouracil 400 mg/m2 and 2400 mg/m2 46-hours continous infusion. Cycle length is 2 weeks +/- 3 days.
• XELOX:Oxaliplatin130 mg/m2.Capecitabine will be 2000 mg/m2 for 14 days. Cycle length is 3 weeks +/- 3 days.

Conditions

Stomach Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS)

  3 years

Secondary Outcomes (9)

• Overall Survival (OS)

  3 years

• Time-to-treatment failure

  3 years

• Overall response rate

  3 years

• Duration of response

  3 years

• Percentage of patients in second line therapy

  3 years

Study Arms (2)

ARM A

EXPERIMENTAL

* RAMUCIRUMAB 8 mg/kg on Days 1 and 15 of every 28-day cycle * PACLITAXEL 80 mg/m2 on Days 1, 8, and 15 of every 28-day cycle until progressive disease, unacceptable toxicity, informed consent withdrawal or patient's death.

Drug: RAMUCIRUMAB; Drug: Paclitaxel

ARM B

ACTIVE COMPARATOR

* FOLFOX4: Oxaliplatin 85 mg/m2 + l-Leucovorin 100 mg/m2 + 5-fluorouracil 400/600 mg/m2. Cycle length is 2 weeks +/- 3 days. * mFOLFOX6: Oxaliplatin a 85 mg/m2+ l-Leucovorin 200 mg/m2 + 5-fluorouracil 400 mg/m2 and 2400 mg/m2 46-hours continous infusion. Cycle length is 2 weeks +/- 3 days. * XELOX:Oxaliplatin130 mg/m2 + Capecitabine will be 2000 mg/m2 for 14 days. Cycle length is 3 weeks +/- 3 days.

Drug: FOLFOX 4; Drug: mFOLFOX 6; Drug: XELOX

Interventions

RAMUCIRUMAB DRUG

Also known as: Cyramza

ARM A

Paclitaxel DRUG

Paclitaxel

ARM A

FOLFOX 4 DRUG

Also known as: Oxaliplatino + l-leucovorin + 5 Fluorouracile

ARM B

mFOLFOX 6 DRUG

Also known as: Oxaliplatino + l-leucovorin + 5 Fluorouracile

ARM B

XELOX DRUG

Also known as: Oxaliplatino + Capecitabina

ARM B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria for study entry:
• Written informed consent prior to performance of any study procedure;
• Age ≥18 years;
• ECOG Performance Status 0-1 (Appendix I);
• Life expectancy of at least 12 weeks in the opinion of the Investigator;
• Unresectable locally advanced or metastatic, histopathologically confirmed, HER-2 negative adenocarcinoma of gastric or GEJ cancer with measurable and/or evaluable disease based on RECIST, v1.1
• Must have received lead-in chemotherapy in the first-line setting using one of the fluoropyrimidines- and oxaliplatin-based doublet combinations as specified in Section 7 and continued for three months (i.e. 6 administrations for bi-weekly cycles regimens or 4 administrations for three-weekly cycles regimens). Patients who had received adjuvant cisplatin/oxaliplatin plus fluoropyrimidine-based doublet chemotherapy and had recurrence beyond 12 months from its completion are eligible.
• Must have radiological evidence of clinical benefit following the last dose of the lead-in chemotherapy (either CR, PR or SD by RECIST v1.1 criteria in case of measurable disease, or absence of progressive disease in case of non-measurable disease).
• Laboratory requirements:
• The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1000/µL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/µL.
• The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases).
• The patient has adequate renal function as defined by a serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed). The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol).
• Coagulation: The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to randomization
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center.
• Archival tumor tissue is required for exploratory research at enrollment.

You may not qualify if:

• Exclude a patient from this study if any of the following conditions are observed:
• HER2 positive status, or the patient has squamous cell.
• Prior malignancy, active within 3 years from study entry, except for locally curable cancers that have been apparently cured and need no subsequent therapy, such as non-melanoma skin cancers, superficial bladder cancer or cancer in situ of the breast or cervix.
• Has a serious illness or medical condition(s) including, but not limited to the following:
• Known brain metastasis or leptomeningeal metastasis.
• Active infection (ie, body temperature ≥38°C due to infection).
• Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
• Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder.
• Uncontrolled diabetes.
• The patient has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
• The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C.
• Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy.
• l.Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results.
• m.The patient has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Maria Di Bartolomeo

Milan, 20133, Italy

RECRUITING

Related Publications (2)

• Randon G, Lonardi S, Fassan M, Palermo F, Tamberi S, Giommoni E, Ceccon C, Di Donato S, Fornaro L, Brunetti O, De Vita F, Bittoni A, Chini C, Spallanzani A, Nappo F, Bethaz V, Strippoli A, Latiano T, Cardellino GG, Giuliani F, Morano F, Niger M, Raimondi A, Prisciandaro M, Pircher CC, Sciortino C, Marchesi S, Garattini SK, Airo G, Miceli R, Di Bartolomeo M, Pietrantonio F. Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer (ARMANI): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 Dec;25(12):1539-1550. doi: 10.1016/S1470-2045(24)00580-1. Epub 2024 Nov 15.

  PMID: 39557058 DERIVED

• Di Bartolomeo M, Niger M, Morano F, Corallo S, Antista M, Tamberi S, Lonardi S, Di Donato S, Berardi R, Scartozzi M, Cardellino GG, Di Costanzo F, Rimassa L, Luporini AG, Longarini R, Zaniboni A, Bertolini A, Tomasello G, Pinotti G, Scagliotti G, Tortora G, Bonetti A, Spallanzani A, Frassineti GL, Tassinari D, Giuliani F, Cinieri S, Maiello E, Verusio C, Bracarda S, Catalano V, Basso M, Ciuffreda L, De Vita F, Parra HS, Fornaro L, Caporale M, de Braud F, Pietrantonio F. Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial. BMC Cancer. 2019 Mar 29;19(1):283. doi: 10.1186/s12885-019-5498-3.

  PMID: 30922323 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Ramucirumab; Paclitaxel; Oxaliplatin; Leucovorin; XELOX; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• MARIA DI BARTOLOMEO

  Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MARIA DI BARTOLOMEO, MD

CONTACT

+390223902882; maria.dibartolomeo@istitutotumori.mi.it

Filippo Pietrantonio, MD

CONTACT

+390223903807; filippo.pietrantonio@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 17, 2016
• Study Start: December 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 13, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)