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Andecaliximab as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Participants With Gastric or Gastroesophageal Junction Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT02862535
Recruitment Status : Active, not recruiting
First Posted : August 11, 2016
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to characterize the safety and tolerability of andecaliximab (GS-5745) as monotherapy and in combination with anti-cancer agents in Japanese participants with inoperable advanced or recurrent gastric or recurrent gastroesophageal junction (GEJ) adenocarcinoma.

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Drug: Andecaliximab Drug: S-1 Drug: Cisplatin Drug: Oxaliplatin Drug: Nivolumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study to Evaluate the Safety and Tolerability of Andecaliximab (GS-5745) as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Subjects With Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date : September 20, 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Andecaliximab Monotherapy (Cohort 1)
Up to 6 participants will receive andecaliximab 800 mg until disease progression. If 2 or more participants experience dose limiting toxicities (DLT) within the first 28 days, up to 6 additional participants will be enrolled to receive andecaliximab 600 mg. If 2 additional DLTs occur at 600 mg, the study will be discontinued.
Drug: Andecaliximab
Administered via intravenous (IV) infusion every 3 weeks
Other Name: GS-5745

Experimental: Combination Therapy Andecaliximab and SP (Cohort 2)
Up to 6 participants will receive andecaliximab 800 mg until disease progression in combination with S-1 plus cisplatin (SP) chemotherapy (dosage and regimen will be based on participant condition, investigator discretion, institutional practice and/or the in-country label). The dose of andecaliximab is based on safety data from cohort 1.
Drug: Andecaliximab
Administered via intravenous (IV) infusion every 3 weeks
Other Name: GS-5745

Drug: S-1
Administered orally twice daily for the first 14 days of the 21 day cycle

Drug: Cisplatin
Administered via IV infusion on Day 8 of every 5 weeks

Experimental: Combination Therapy Andecaliximab and SOX (Cohort 3)
Up to 10 participants will receive andecaliximab 1200 mg until disease progression in combination with 80 mg/day to 120 mg/day S-1 depending on body surface area (BSA) plus 100mg/m^2 oxaliplatin (SOX) chemotherapy. The dose of andecaliximab is based on safety data from cohort 1 and other ongoing phase 1 studies of andecaliximab.
Drug: Andecaliximab
Administered via intravenous (IV) infusion every 3 weeks
Other Name: GS-5745

Drug: S-1
Administered orally twice daily for the first 14 days of the 21 day cycle

Drug: Oxaliplatin
Administered via IV infusion on Day 1 of each 21-day cycle

Experimental: Combination Therapy Andecaliximab and Nivolumab (Cohort 4)
Up to 10 participants will receive andecaliximab 800 mg until disease progression in combination with 3 mg/kg nivolumab chemotherapy. The dose of andecliximab is based on safety data from cohort 1.
Drug: Andecaliximab
Administered via intravenous (IV) infusion every 3 weeks
Other Name: GS-5745

Drug: Nivolumab
Administered via IV infusion every 2 weeks




Primary Outcome Measures :
  1. Overall Safety Profile of Andecaliximab [ Time Frame: Baseline up to the last dose date plus 30 days (maximum: 6 months) ]
    The overall safety profile of andecaliximab will be assessed as the percentage of participants experiencing treatment-emergent adverse events (AE), abnormal physical examinations, abnormal 12-lead electrocardiograms (ECG), abnormal vital signs, and abnormal clinical laboratory test findings.


Secondary Outcome Measures :
  1. Plasma Concentrations of Andecaliximab [ Time Frame: Predose and 30 (±15) minutes postdose ]
  2. PK Parameter: Cmax of Andecaliximab [ Time Frame: Predose and 30 (±15) minutes postdose ]
    Cmax is defined as the maximum concentration of drug.

  3. PK Parameter: AUC of Andecaliximab [ Time Frame: Predose and 30 (±15) minutes postdose ]
    AUC is defined as the concentration of drug over time.

  4. Incidence Rate of Positive Anti-Andecaliximab Antibodies [ Time Frame: Baseline up to the last dose date plus 30 days (maximum: 6 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1
  • Must be able to trace their maternal and paternal ancestry of parents and grandparents as ethnically Japanese
  • Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the GEJ) or relapsed gastric adenocarcinoma
  • Cohorts 1, 2, and 3: Human Epidermal Growth Factor Receptor 2 (HER2)‑negative tumor (primary tumor or metastatic lesion)). Enrollment in Cohort 4 is not restricted by HER2 status (adults with HER2‑positive, HER2-negative, or unknown HER2 status are eligible)
  • Cohort 1: Prior antitumor therapy or cytotoxic chemotherapy is acceptable. Individuals who are not eligible to receive standard treatments should enroll on the study.
  • Cohorts 2 and 3: Prior antitumor therapy or cytotoxic chemotherapy for metastatic disease is not acceptable. Individuals must be chemo-naive in the metastatic setting.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Adequate baseline organ function (within 28 days prior to Day 1)
  • Coagulation: International Normalized Ratio (INR) ≤ 1.5 (unless receiving anticoagulation therapy).
  • For females of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for defined periods following the last dose of andecaliximab and/or anti-cancer agent(s)
  • For males of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of andecaliximab, throughout the study treatment period, and for protocol defined periods following the last dose of andecaliximab and/or anti-cancer agent(s)
  • Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions
  • In addition to the applicable criteria above, participants in Cohort 4 must meet additional inclusion criteria to be eligible for participation in this study:

    • Measureable gastric or GEJ adenocarcinoma
    • Must have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic disease.
    • Activated partial thromboplastin (aPTT) ≤ 1.5 times the upper limit of normal.
    • Thyroid function tests should be within normal limits.

Key Exclusion Criteria:

  • History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator and medical monitor would pose a risk to participant safety or interfere with the study evaluations, procedures, or completion
  • Pregnant or lactating. Enrollment of lactating females after discontinuation of breastfeeding is not acceptable.
  • Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids
  • Radiotherapy within 28 days of Day 1
  • Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Day 1
  • History of major surgery within 28 days of Day 1
  • Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires IV antibiotics
  • Individuals known to be positive for human immunodeficiency virus (HIV), hepatitis C infection (per local standard diagnostic criteria), or acute or chronic hepatitis B infection (per local standard diagnostic criteria)
  • In addition to the applicable criteria above, paricipants in Cohort 4 who meet any of the following exclusion criteria will not be enrolled in this study:

    • Have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
    • Prior treatment with anti-CTLA-4 agents, anti PD-1 or anti-PD-L1 agents, anti-PD-L2 agents, anti-MMP agents, or other immunomodulatory therapies

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


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): NCT02862535


Locations
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Japan
Nagoya, Japan
Osaka, Japan
Tokyo, Japan
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02862535     History of Changes
Other Study ID Numbers: GS-US-296-1884
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cisplatin
Oxaliplatin
Nivolumab
Antineoplastic Agents
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs