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Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02625623
First Posted: December 9, 2015
Last Update Posted: September 27, 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 plus best supportive care (BSC) versus physician's choice (chosen from a pre-specified list of therapeutic options) plus BSC.

Condition Intervention Phase
Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Gastric Cancer Third Line Drug: Avelumab Drug: Irinotecan Drug: Paclitaxel Other: Best Supportive Care (BSC) 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 Avelumab (MSB0010718C) as a Third-line Treatment of Unresectable, Recurrent, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 years) ]
    Time (in months) from randomization to the date of death, regardless of the actual cause of the subject's death


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 years) ]
    PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS will be assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD is defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Best Overall Response (BOR) [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 years) ]
    BOR will be determined according to RECIST 1.1 and as adjudicated by an Independent Review Committee (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 disease progression 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 sum of the longest diameter (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 percent (%) 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 (EQ-5D-5L) Health Outcome Questionnaire [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 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) Global Health Status [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 years) ]
    EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer subjects. 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 GHS/QoL score ranges from 0 to 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 the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC STO22) Questionnaire Scores [ Time Frame: Until 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized (assessed up to 2 years) ]
    The QLQ-STO22 is a gastric cancer quality of life 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.


Enrollment: 376
Actual Study Start Date: December 28, 2015
Estimated Study Completion Date: September 20, 2022
Estimated Primary Completion Date: March 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avelumab+Best Supportive Care (BSC) Drug: Avelumab
Avelumab will be administered as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with best supportive care (BSC).
Other Names:
  • MSB0010718C
  • Anti PD-L1
Other: Best Supportive Care (BSC)
BSC is defined as treatment administered with the intent to maximize Quality of life without a specific antineoplastic regimen and is based on investigator's discretion. BSC will be administered once every 3 weeks.
Active Comparator: Physician's choice chemotherapy+BSC or BSC alone

Physician's choice chemotherapy comprises of the following:

Paclitaxel or

Irinotecan

Subjects who are not deemed eligible to receive Paclitaxel or Irinotecan at the dose and schedule specified will receive BSC as per investigator discretion and visit the clinic once every 3 weeks.

Drug: Irinotecan
Irinotecan will be administered at a dose of 150 mg/m ^2 on Day 1 and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.
Drug: Paclitaxel
Paclitaxel will be administered at a dose of 80 mg/m^2 on Day 1, 8, and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.
Other: Best Supportive Care (BSC)
BSC is defined as treatment administered with the intent to maximize Quality of life without a specific antineoplastic regimen and is based on investigator's discretion. BSC will be administered once every 3 weeks.

  Eligibility

Information from the National Library of Medicine

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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
  • Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
  • Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue
  • Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry
  • Adequate hematological, 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
  • Major surgery
  • 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 less than [<] 10 mg prednisone daily).
  • All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, 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 of grade >2 related to prior therapy except alopecia
  • Neuropathy Grade greater than or equal (>=) 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 within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  • Legal incapacity or limited legal capacity
  • Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization
  • Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call
  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): NCT02625623


  Show 75 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02625623     History of Changes
Other Study ID Numbers: EMR 100070-008
2015-003301-42 ( EudraCT Number )
First Submitted: December 4, 2015
First Posted: December 9, 2015
Last Update Posted: September 27, 2017
Last Verified: September 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Avelumab
Gastric cancer
Gastroesophageal junction adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Paclitaxel
Irinotecan
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs