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

NCT ID: NCT05535569

Last Updated: 2022-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-17
• Study Completion Date: 2021-11-22

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.

Detailed Description

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.

Patients who are EBV-related, MSI-high, or PD-L1 positive will be confirmed by immunohistochemistry (IHC) in a central laboratory (Yonsei Cancer Center), and who meet all eligibility criteria will be enrolled to this study and receive treatment with nivolumab and paclitaxel until progressive disease is confirmed or at least 1 discontinuation criterion is met. It was assumed that about 15% of screened patients will be categorized EBV-related, MSI-high, or PD-L1 positive gastric cancer based on previously reported study results. Part 1>> Phase Ib Phase Ib: 6-12 (The actual number of subjects will be determined by the number of dose escalations to identify MTD and RP2D) Part 2>> Phase II - At the RP2D dose level in phase I part, we will expand phase 2 study for a total of 50 patients. Patients will be treated until the time of disease progression, intolerable toxicities, patient's refusal or consent withdrawal. Tumor assessment will be done every 6 weeks.

Conditions

Recurrent/Metastatic Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Group Type: EXPERIMENTAL

Nivolumab, Paclitaxel

Intervention Type: 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.

Interventions

Nivolumab, Paclitaxel

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Has provided digned written informed Consent

2. Is male or female ≥19 years of age

3. Has a histologically or cytologically confirmed diagnosis of advanced gastric adenocarcinoma

4. Has documented EBV-related, MSI-high, or PD-L1 positive tumor in primary or metastatic tumor tissue

5. Has a life expectancy of at least 3 months

6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Has measurable or evaluable disease as determined by RECIST 1.1.

8. Is able to swallow and retain orally administered medication

9. 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.

Exclusion Criteria

1. Has HER2-positive or indeterminate gastric cancer

2. Have multiple cancers

3. Have a current or past history of severe hypersensitivity to any other antibody products

4. Have concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease

5. Have a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging (preferably CT) or clinical findings

6. Have brain or meninx metastases. Patients may be randomized for the study if they are asymptomatic and require no treatment.

7. Have pericardial fluid, pleural effusion, or ascites requiring treatment

8. Have a history of uncontrollable or significant cardiovascular disease

9. Have systemic infection requiring treatment

10. Are contraindicated for paclitaxel

11. Has had prior treatment with:

• Require or, within 28 days before treatment, have received systemic corticosteroids or immunosuppressants

12. Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment

13. Have received radiotherapy for gastric cancer within 28 days before treatment or radiotherapy for bone metastases within 14 days before treatment

14. Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody,

15. Hepatitis B surface protein (HBs) antigen and HBV titer >2000 IU/ml (10,000 copy/ml), or hepatitis C virus (HCV) antibody positive result

16. Are pregnant or breastfeeding, or possibly pregnant

17. Has any unresolved ≥Grade 2 (per CTCAE v4.0) toxicity from previous anti-cancer therapy at the time of enrollment such as neuropathy, except alopecia or anemia

18. Have previously received nivolumab, anti-programmed cell death-1 (PD-1) antibody, anti-PD-L1 antibody, anti-programmed cell death-ligand 2 (PD-L2) antibody, anti-CD137 antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody, or other therapeutic antibodies or pharmacotherapies for the regulation of T-cells

19. Are incapable of providing consent for specific reasons, such as concurrent dementia

20. Are otherwise inappropriate for this study in the investigator's or subinvestigator's opinion.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

SUN YOUNG RHA

Role: PRINCIPAL_INVESTIGATOR

Yonsei Cancer Center, Yonsei University College of Medicine

Locations

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2017-0277

Identifier Type: -

Identifier Source: org_study_id