Phase Ib/II Study to Evaluate the Safety and Efficacy of Nivolumab in Combination With Paclitaxel in Epstein-Barr Virus(EBV)-Related, or Microsatellite Instability-High (MSI-H), or Programmed Cell Death Ligand 1 (PD-L1) Positive Advanced Gastric Cancer

NCT05535569 | Completed Phase 1 DMC

• 1 other identifier: 4-2017-0277
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib/II study to identify the recommended dose of paclitaxel and nivolumab for further study, and to assess the safety and clinical efficacy of this combined treatment in EBV-related, MSI-high, or PD-L1 positive advanced gastric cancer after first line treatment.

Conditions

Recurrent/Metastatic Gastric Cancer

Keywords

Epstein-Barr Virus(EBV)-Related, or Microsatellite Instability-High (MSI-H), or Programmed Cell Death Ligand 1 (PD-L1) Positive Advanced Gastric Cancer; Nivolumab

Outcome Measures

Primary Outcomes (3)

• (Phase Ib) Maximum Tolerated dose (MTD)

  Maximum Tolerated dose (MTD) as determined by Dose limiting Toxicity (DLT).

  424 weeks

• (Phase Ib) Recommended phase 2 dose

  Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).

  424 weeks

• (Phase II) PFS

  Progression-free survival (PFS): Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria. PFS is defined as the interval between the date of first dose and the earliest date of disease progression or death due to any cause.

  424 weeks

Secondary Outcomes (4)

• OS

  24 weeks

• ORR

  24 weeks

• DCR

  24 weeks

• PFS

  24 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

Drug: Nivolumab, Paclitaxel

Interventions

Nivolumab, Paclitaxel DRUG

Increasing dose levels of paclitaxel (70 mg/m2 or 80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle) in combination with a fixed dose of nivolumab (3 mg/kg on Days 1 and 15 of a 28-day treatment cycle) will be explored using a 3+3 design to evaluate the safety and tolerability and to determine a MTD.

Experimental

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided digned written informed Consent
• Is male or female ≥19 years of age
• Has a histologically or cytologically confirmed diagnosis of advanced gastric adenocarcinoma
• Has documented EBV-related, MSI-high, or PD-L1 positive tumor in primary or metastatic tumor tissue
• Has a life expectancy of at least 3 months
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has measurable or evaluable disease as determined by RECIST 1.1.
• Is able to swallow and retain orally administered medication
• Has an adequate baseline organ function defined as:
• White blood cells ≥3000/mm3 and neutrophils ≥1500/mm3
• Platelets ≥100000/mm3
• Hemoglobin ≥9.0 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)
• Total bilirubin ≤2.0 × ULN
• Creatinine≤1.5 × ULN or creatinine clearance (either measured value or estimated value using the Cockcroft-Gault equation) \>60ml/min.

You may not qualify if:

• Has HER2-positive or indeterminate gastric cancer
• Have multiple cancers
• Have a current or past history of severe hypersensitivity to any other antibody products
• Have concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease
• Have a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging (preferably CT) or clinical findings
• Have brain or meninx metastases. Patients may be randomized for the study if they are asymptomatic and require no treatment.
• Have pericardial fluid, pleural effusion, or ascites requiring treatment
• Have a history of uncontrollable or significant cardiovascular disease
• Have systemic infection requiring treatment
• Are contraindicated for paclitaxel
• Has had prior treatment with:
• \- Require or, within 28 days before treatment, have received systemic corticosteroids or immunosuppressants
• Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment
• Have received radiotherapy for gastric cancer within 28 days before treatment or radiotherapy for bone metastases within 14 days before treatment
• Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody,

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; Paclitaxel

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

Study Officials

• SUN YOUNG RHA

  Yonsei Cancer Center, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 10, 2022
• Study Start: July 17, 2017
• Primary Completion: November 22, 2021
• Study Completion: November 22, 2021
• Last Updated: September 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)