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Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02625610
First Posted: December 9, 2015
Last Update Posted: December 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
  Purpose
The purpose of this study is to demonstrate superiority of treatment with avelumab versus continuation of first-line chemotherapy.

Condition Intervention Phase
Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction Drug: Avelumab Drug: Oxaliplatin Drug: 5-Fluorouracil Drug: Leucovorin Drug: Capecitabine Other: Best supportive care Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Open-label, Multicenter Trial of Maintenance Therapy With Avelumab (MSB0010718C) Versus Continuation of First-line Chemotherapy in Subjects With Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro-esophageal Junction

Resource links provided by NLM:


Further study details as provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Primary Outcome Measures:
  • Overall Survival (OS) Time [ Time Frame: From the date of randomization up to 30 months ]
    OS is defined as the time (in months) from randomization to the date of death, regardless of the actual cause of the subject's death.

  • Progression-Free Survival (PFS) Time [ Time Frame: From the date of randomization up to 30 months ]
    PFS is defined as time (in months) from date of randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause in the absence of documented PD (whichever occurs first). PFS will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as adjudicated by an independent review committee (IRC). PD is defined as at least a 20 percent (%) increase in the sum of longest diameters (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.


Secondary Outcome Measures:
  • Best overall response (BOR) [ Time Frame: From the date of randomization up to 22 months ]
    BOR will be determined according to RECIST 1.1 and as adjudicated by an IRC. BOR is defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until PD or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Change from baseline in European Quality Of Life 5-dimensions-5 levels (EQ-5D-5L) Health Outcome Questionnaire [ Time Frame: From baseline and Weeks 4, 7, 13 and then every 6 weeks until 12 weeks after last treatment, assessed up to 3 years ]
    The EQ-5D-5L Health Outcome Questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest is 1.00 (no problems in all 5 dimensions).

  • Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) [ Time Frame: From baseline and Weeks 4, 7, 13 and then every 6 weeks until 12 weeks after last treatment, assessed up to 3 years ]
    The European Organization for Research and Treatment of Cancer (EORTC) Core QoL questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 Global Health Status/QoL scale is scored between 0 and 100. High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

  • Change from baseline in European Organization for Research and Treatment of Cancer Gastric Cancer Module QLQ-STO22 [ Time Frame: From baseline and Weeks 4, 7, 13 and then every 6 weeks until 12 weeks after last treatment, assessed up to 3 years ]
    The QLQ-STO22 is a gastric cancer quality of life (QoL) questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). For the symptom scales or single items, participants will be assessed using a 4-point scale (1=not at all; 2=a little; 3=quite a bit; 4=very much). All scales and single-item scores ranged from 0 to 100. For the symptom scales or single items, a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.

  • Number of subjects with Treatment-Emergent Adverse Events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [ Time Frame: From the first dose of study drug administration up to 28 days after the last dose of study drug administration, assessed up to 3 years ]
    TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 28 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.


Estimated Enrollment: 466
Actual Study Start Date: December 24, 2015
Estimated Study Completion Date: March 11, 2024
Estimated Primary Completion Date: March 13, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avelumab

Induction Phase: Subjects will be administered with oxaliplatin and either 5-Fluorouracil (5-FU) or capecitabine for 12 weeks.

Maintenance Phase: Subjects will be administered with IV infusion of avelumab once every 2 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation

Drug: Avelumab
Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Drug: Oxaliplatin
Oxaliplatin will be administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks.
Drug: 5-Fluorouracil
Induction Phase: 5-Fluorouracil will be administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks.
Drug: Leucovorin
Induction Phase: Leucovorin will be administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.
Drug: Capecitabine
Induction Phase: Capecitabine will be administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.
Active Comparator: Oxaliplatin-fluoropyrimidine doublet

Induction Phase: Subjects will be administered with oxaliplatin and either 5-FU or capecitabine for 12 weeks.

Maintenance Phase: Subjects will continue the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5-FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Subjects who are not deemed eligible to receive further chemotherapy will receive best supportive care (BSC) alone with no active therapy.

Drug: Oxaliplatin
Induction Phase: Oxaliplatin will be administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks. Maintenance Phase: Subjects will continue the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Drug: 5-Fluorouracil
Induction Phase: 5-Fluorouracil will be administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks. Maintenance Phase: Subjects will continue the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Drug: Leucovorin

Induction Phase: Leucovorin will be administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.

Maintenance Phase: Subjects will continue the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.

Drug: Capecitabine

Induction Phase: Capecitabine will be administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.

Maintenance Phase: Subjects will continue the same regimen of chemotherapy as they received during the Induction Phase every 3 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.

Other: Best supportive care
Treatment administered with the intent to maximize Quality of Life (QoL) without a specific antineoplastic regimen. These may include for example antibiotics, analgesics, antiemetics, thoracentesis, paracentesis, blood transfusions, nutritional support (including jejunostomy), and focal external-beam radiation for control of pain, cough, dyspnea, or bleeding. Best supportive care will be administered per institutional guidelines and subjects will visit the clinic every 3 weeks.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged greater than or equal to (>=) 18 years
  • Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  • Subjects with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
  • Estimated life expectancy of more than 12 weeks
  • Adequate haematological, hepatic and renal functions defined by the protocol
  • Negative blood pregnancy test at Screening for women of childbearing potential
  • Highly effective contraception for both male and female subjects if the risk of conception exists
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
  • Concurrent anticancer treatment or immunosuppressive agents
  • Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
  • Tumor shown to be human epidermal growth factor 2 plus (HER2+)
  • Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
  • Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to <= 10 mg prednisone daily).
  • All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
  • Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
  • Prior organ transplantation, including allogeneic stem-cell transplantation
  • Significant acute or chronic infections
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
  • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
  • Persisting toxicity related to prior therapy except alopecia
  • Neuropathy Grade > 3
  • Pregnancy or lactation
  • Known alcohol or drug abuse
  • History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
  • Clinically significant (i.e., active) cardiovascular disease
  • All other significant diseases might impair the subject's tolerance of trial treatment
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
  • Vaccination with live or live/attenuated viruses within 55 days of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  • Legal incapacity or limited legal capacity
  • Patients will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
  • Other protocol defined exclusion criteria could apply
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02625610


  Show 202 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc. a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02625610     History of Changes
Other Study ID Numbers: EMR 100070-007
2015-003300-23 ( EudraCT Number )
First Submitted: December 4, 2015
First Posted: December 9, 2015
Last Update Posted: December 1, 2017
Last Verified: November 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Avelumab
Cancer
Unresectable
Locally advanced
Metastatic
Adenocarcinoma of the stomach
Gastro-esophageal junction

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Capecitabine
Fluorouracil
Oxaliplatin
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs