Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Gastric Adenocarcinoma Clinical Trial

— GAMMA-1  

Official title:

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-5745 Combined With mFOLFOX6 as First Line Treatment in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02545504
• Other study ID #: GS-US-296-1080
• Secondary ID: 2015-001526-42
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2015
• Est. completion date: May 15, 2019

Study information

• Verified date: May 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the efficacy of andecaliximab (GS-5745) versus placebo in combination with modified fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (OXA) (mFOLFOX6) as measured by overall survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 432
• Est. completion date: May 15, 2019
• Est. primary completion date: May 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy

• Adequate hematologic, liver, coagulation and kidney function

• Eastern Cooperative Oncology Group (ECOG) = 1

• Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1

Key Exclusion Criteria:

• Previous chemotherapy for locally advanced or metastatic gastric cancer.

• Human Epidermal Growth Factor Receptor 2 (HER2)-positive gastric cancer

• HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection

• Pregnant or breast feeding women

• Individuals with known or suspected central nervous system metastases or individuals requiring chronic daily treatment with oral corticosteroids

• Grade = 2 peripheral neuropathy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma

Intervention

Drug:
• Andecaliximab
800 mg administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• Placebo
Administered intravenously on Days 1 and 15 of each treatment cycle
• Leucovorin
Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
• 5-fluorouracil
Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
• Oxaliplatin
Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	The Canberra Hospital	Garran	Australian Capital Territory
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Ashford Cancer Centre	Kurralta Park	South Australia
Australia	Epworth Healthcare	Richmond	Victoria
Australia	Western Health Sunshine Hospital	St Albans	Victoria
Australia	The Tweed Hospital	Tweed Heads
Australia	Sydney Adventist Hospital	Wahroonga
Australia	The Crown Princess Mary Cancer Centre	Westmead	New South Wales
Belgium	University Hospital Gent Department of Gastroenterology	Gent
Belgium	Centre Hospitalizer De L'Ardenne	Libramont	Chevigny
Chile	Instituto Nacional Del Cancer	Santiago
Chile	Instituto Clinico Oncologico del Sur	Temuco
Chile	Hospital Clinico Vina Del Mar	Vina del Mar
Colombia	Dundacion Oftalmologica de Santander Clinica Ardila Lulle La Foscal	Floridablanca
Colombia	Hospital Pablo Tobon Uribe	Medellin
Colombia	Oncomedica S.A	Monteria	Cordoba
Colombia	Centro Medico Imbanaco de Cali S.A	Valle
Czechia	Fakultni Nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	University Hospital - Czech	Olomouc
Czechia	Thomayer Hospital	Prague 4
Czechia	Oblastni Nemocnice Pribram	Pribram
France	CHU Jean Minjoz	Besancon
France	CHRU de Brest, Hopital Morvan, Institut de Cancerologie et d'Hematologie	Brest Cedex
France	Hôpitaux Civils de Colmar	Colmar
France	Institut Paoli Calmettes	Marseille Cedex 9
France	CHU de Nice-l Archet	Nice Cedex 3
France	CH Annecy-Gennevois	Pringy Cedex
Germany	DRK Klinken Berlin Abteilungsleiter Chiurgische Okologie	Berlin
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Kliniken Essen Mitte Studiensekretariat Onkologie Evang. Huyssens-Stiftung	Essen
Germany	Krankenhaus Nordwest gGmbH Institut für Klinisch Onkologische Med Klinik II	Frankfurt
Germany	Cancer Center Heilbronn-Franken, SLK-Kliniken	Heilbronn
Germany	Staedtisches Klinikum Muenchen Bogenhausen	Muenchen
Germany	Klinikum rechts der Isar Technical University of Ismaninger	Munich	Bayern
Germany	Zentrum fur Innere Medizin Stauferklinikum Schwab	Mutlangen
Germany	Universitatsklinikum Ulm	Ulm
Germany	Kliniken Nordoberpfalz AG	Weiden	Bavaria
Hungary	Egyesített Szent István és Szent László Kórház -Rendelointézet	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Hungary	Human Klinikai Vizsgalatok Regisztracios Kozpont - HKVRK	Gyor
Hungary	Pandy Kalman Hospital	Gyula
Hungary	Borsod County Hospital Clinical Oncological and Radiotheraputic Center	Miskolc
Hungary	Zala Megyei Korhaz Pozva Diabetes Kulsokorhaz	Zalaegerszeg
Italy	Ente Ospedaliero Ospedali Galliera	Genova
Italy	IRCCS A.O.U. San Martino	Genova
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Ospedale San Raffaele	Milano
Italy	University Hospital Company of Pisana	Pisa	PI
Italy	S.C. Oncologia Medica Azienda Ospedaliera Valtellina e Valchiavenna Presidio Ospedaliero di Sondrio	Sondrio
Italy	Azienda Ospedaliera Treviglio Caravaggio U.O. Oncologia Medica	Treviglio
Peru	Centro Medico monte Carmelo	Arequipa
Peru	Centro de Investigacion Instituto de oncologia y Radiotherpia de la Clinica	San Isidro	Lima
Peru	Clinica Anglo Americana Calle Alfredo Salazar	San Isidro
Poland	Beskidzkie Oncology Center	Bielsko-Biala
Poland	Wojewodzki Szpital Zespolony w Elblagu Oddzial Onkologiczny	Elblag
Poland	Wielkopolskie Centrum Onkologii	Poznan
Poland	Mrukmed Lekarz Beata Madej Mruk i Partner Spolka Partnerska Oddzial Nr 1 w Rzeszowie	Rzeszow
Poland	Wojewodzki Szpital Zespolony im L Rydygiera w Toruniu	Torun
Poland	Wojskowy Instytut Medyczny	Warsaw
Poland	Klinka Gastroenterologii Okologicznej Centrum Okologii Instytut	Warszawa
Romania	Fundeni Clinical Institute	Bucuresti
Romania	GRAL Medical SRL	Bucuresti
Romania	Medisprof srl Oncologie P TA	Cluj-Napoca	Judet Cluj
Romania	Centrul de Oncologie Sfantul Nectarie SRL, Oncologie	Craiova
Romania	Sc Oncolab Srl	Craiova
Romania	SC Centrul de Oncologie Euroclinic SRL, Oncologie	Iasi
Romania	Spitalul Judetean De Urgenta Sf Ion Cel Nou Suceava Sectia Oncologie Medicala Bdul	Suceava
Spain	Hospital Universitario de A Coruna C	A Coruna
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Del Mar Servicio de Oncologia	Barcelona
Spain	Hospital Parc Tauli	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala de la Salut	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Morales Meseguer	Murcia
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Virgen de Valme	Sevilla
Turkey	Cukurova Universitesi	Adana
Turkey	Ankara University Medical Faculty Ibni Sina Hospital	Ankara
Turkey	Hacettepe Universitesi Tip Facultesi Cocuk Saligi ve Hastaklikleri Anabilim Dali	Ankara
Turkey	Hacettepe University	Ankara
Turkey	University of Uludag	Bursa
Turkey	Trakya University	Edirne
Turkey	Bezmialem University Hospital	Istanbul
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Istanbul
Turkey	Istanbul Universitesi Onkoloji Enstitusu Medikal Onkoloji Bilim Dali	Istanbul
Turkey	Marmara University	Kadikoy
Turkey	Izmir Universitesi Hastanesi Yeni Girne Vulvari	Karsiyaka
Turkey	Kocaeli Universty	Kocaeli
Turkey	Inonu Universitesi Turgut Ozal Tip Merkezi Elazi	Malatya
Turkey	Van Yuzuncu Yil Universitesi Tip Kaultesi Ic Hastaliklari Anabilim Dali Tibbi Okoloji Bilim Dali	Van
United Kingdom	New Queen Elizabeth Hospital	Birmingham
United Kingdom	Peterborough City Hospital Peterborough and Stamford Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Royal Marsden Hospital Mulberry House	London
United Kingdom	University College London	London
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	The Ohio State Medical Center	Columbus	Ohio
United States	Omega Research Consultants LLC	DeBary	Florida
United States	Karamanos Cancer Institute	Detroit	Michigan
United States	Duke Cancer Institute	Durham	North Carolina
United States	Parkview Hospital	Fort Wayne	Indiana
United States	Center for Cancer Blood Disorders	Fort Worth	Texas
United States	Indiana University Goshen Center for Cancer Care	Goshen	Indiana
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	HCA Healthcare	Kansas City	Missouri
United States	Scripps Green Hospital	La Jolla	California
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Edward Hospital & Health Services	Naperville	Illinois
United States	Tennessee Oncology	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Cancer Center of Central Connecticut	Plainville	Connecticut
United States	Northwest Cancer Specialists	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	Texas Oncology-Seton Williamson	Round Rock	Texas
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	New England Cancer Specialists	Scarborough	Maine
United States	Virginia Mason Seattle Main Clinic	Seattle	Washington
United States	Regional Cancer Care Associates LLC - Sparta	Sparta	New Jersey
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Prairie Lakes Health Care System INC	Watertown	South Dakota
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Chile,  Colombia,  Czechia,  France,  Germany,  Hungary,  Italy,  Peru,  Poland,  Romania,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

Shah et al A phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of andecaliximab combined with mFOLFOX6 as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma (GAMMA-1)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS was defined as the time interval from the date of randomization to death from any cause.	Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months
Secondary	Progression-free Survival (PFS)	PFS was defined as the interval of time from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause.	Andecaliximab + mFOLFOX6 median follow-up at the time of the final analysis: 18.64 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 18.74 months
Secondary	Objective Response Rate (ORR)	ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to 135.4 weeks at the time of final analysis
Secondary	Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events in a given study period that meet any of the following criteria: Any AE with onset date of on or after andecalizimab/placebo start date and no later than 30 days after permanent discontinuation of all study treatment (andecaliximab/placebo and chemotherapy) or Any AEs with onset date of on or after the andecaliximab/placebo start date and no later than 55 days after permanent discontinuation of andecaliximab/placebo or AEs leading to discontinuation of andecaliximab/placebo.	First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days
Secondary	Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to 30 days after the last dose of all study treatment, or 55 days after the last dose of andecaliximab/placebo for participants who permanently discontinued all study treatments. If the relevant baseline laboratory value is missing, then any abnormality of at least Grade 1 was considered treatment-emergent.	First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days