Nivolumab Adding on Gemcitabine/S-1 in Metastatic Pancreatic Cancer

NCT04377048 | Unknown Phase 2

• 1 other identifier: 202001045MIPA
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study assumes that to achieve significant therapeutic efficacy in advanced pancreatic cancer with immunotherapy, the immune system must remain relatively intact. Therefore, early use, low tumor load, adequate organ function, and slow growth of the tumor are the key points. Stage IV pancreatic adenocarcinoma patients with limited metastatic lesions and adequate organ function will be enrolled. Gemcitabine plus S-1 (GS) will be administered initially, and then CA 19-9 will be evaluated. Those fulfilling pre-defined criteria of CA 19-9 will receive nivolumab add-on therapy.

Conditions

Stage IV Pancreatic Cancer

Keywords

pancreatic adenocarcinoma; chemotherapy; nivolumab

Outcome Measures

Primary Outcomes (1)

• response rate

  overall response rate of gemcitabine/S-1/nivolumab

  6 weeks

Study Arms (1)

Nivolumab/GS

EXPERIMENTAL

Part-1: GS Induction * Patients will receive GS for 1 cycle. * S-1: 60/80/100 mg per day (based on body surface area, BSA); D1-12; 3 weeks per cycle * BSA \< 1.25 m2: 60 mg/day; 1.25 m2 ≤ BSA \< 1.5 m2: 80 mg/day; BSA ≥ 1.5 m2: 100 mg/day * Gemcitabine: 850 mg/m2; D1, 8; 3 weeks per cycle * After GS, patients fulfilling the pre-defined CA 19-9 criteria will enter the Add-On part. Part-2: Nivolumab Add-On * Nivolumab: 3 mg/kg every 2 weeks, 6 weeks per cycle * S-1: according to the individualized dose on D8 of cycle 1 in Part-1, 6 weeks per cycle * Gemcitabine: according to the individualized dose on D8 of cycle 1 in Part-1, 6 weeks per cycle The treatment will be continued until disease progression, intolerance to study treatment or death.

Drug: Nivolumab; Drug: Gemcitabine; Drug: Tegafur-Gimeracil-Oteracil

Interventions

Nivolumab DRUG

as described in "NGS Arm"

Nivolumab/GS

Gemcitabine DRUG

as described in "NGS Arm"

Nivolumab/GS

Tegafur-Gimeracil-Oteracil DRUG

as described in "NGS Arm"

Also known as: S-1

Nivolumab/GS

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically proven pancreatic adenocarcinoma
• newly diagnosed, stage IV pancreatic cancer with limited metastases and tumor burden
• no previous radiotherapy, chemotherapy, targeted therapy, curative surgery, local therapy (eg. radiofrequency ablation, irreversible electroporation, etc.), immunotherapy, cell therapy (autologous or allogenic) used for pancreatic cancer
• presence of at least one measurable lesion at the pancreas and at least one measurable metastatic lesion
• age between 20 and 75 years at registration
• ECOG performance status of 0 or 1
• adequate major organ functions
• baseline CA 19-9 \> upper limit of normal
• Glasgow prognostic score of 0 (ie. albumin ≥ 3.5 g/dL and CRP ≤ 1 mg/dL)
• ability to take study medication (S-1) orally
• no clinically significant abnormal ECG findings within 28 days prior to registration
• Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) must agree to use contraception from the time of informed consent until 5 months or more after the last dose of investigational products. Also, women must agree not to breastfeed from the time of informed consent until 5 months or more after the last dose of the investigational product.
• Men must agree to use contraception from the start of study treatment until 7 months or more after the last dose of the investigational product.
• Sign written informed consent

You may not qualify if:

• interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity within 28 days prior to registration
• presence of diarrhea ≥ CTCAE v.5.0 grade 2
• concomitant systemic infection requiring treatment
• clinically significant co-morbid medical conditions, including cardiovascular disease known autoimmune disease
• concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
• prior organ allograft or allogeneic bone marrow transplantation
• received systemic corticosteroids (except for temporary use, e.g., for examination or prophylaxis of allergic reactions) or immunosuppressants within 28 days before registration
• HBV (positive HBsAg or HBV DNA) or HCV carrier (positive anti-HCV or HCV RNA)
• known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
• moderate or severe ascites, pleural effusion, or pericardial effusion requiring treatment
• central nervous system metastasis
• prior or concurrent malignancies within the last 3 years, with the exception of carcinoma in situ of the cervix, or basal type skin cancer
• concomitant treatment with flucytosine, phenytoin or warfarin
• any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
• transfusion from 72 hours prior to registration to the first dose of study drug administration

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Ono Pharmaceutical Co. Ltd: collaborator
• ACT Genomics: collaborator
• TTY Biopharm: collaborator

Related Publications (3)

• Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. doi: 10.1200/JCO.2012.43.3680. Epub 2013 Apr 1.

  PMID: 23547081 RESULT

• Weiss GJ, Blaydorn L, Beck J, Bornemann-Kolatzki K, Urnovitz H, Schutz E, Khemka V. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018 Feb;36(1):96-102. doi: 10.1007/s10637-017-0525-1. Epub 2017 Nov 8.

  PMID: 29119276 RESULT

• Yang SH, Chen BB, Lee JC, Kuo YT, Kuo SH, Cheng AL, Yeh KH. Incorporating nivolumab with preceded gemcitabine and S-1 chemotherapy for patients of metastatic pancreatic cancer: a pilot study. Am J Cancer Res. 2025 Sep 25;15(9):4108-4120. doi: 10.62347/NJOX8790. eCollection 2025.

  PMID: 41113977 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Gemcitabine; tegafur-gimeracil-oteracil; S 1 (combination)

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Shih-Hung Yang, M.D., Ph.D.

  Department of Oncology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shu-Ling Wu

CONTACT

+886-2-23123456; shulingwu.ntuh@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon's two-stage design

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 6, 2020
• Study Start: July 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: December 31, 2022
• Last Updated: May 6, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share