Clinical Study of Regorafenib and Nivolumab Plus Chemotherapy

NCT05394740 | Completed Phase 1

• 1 other identifier: EPOC2104
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, single-center Phase Ib/II study to exploratorily evaluate the tolerability, safety, and efficacy of regorafenib and nivolumab plus chemotherapy in patients with unresectable advanced/recurrent gastric/ gastroesophageal junction/esophageal adenocarcinoma.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma

Keywords

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma; Regorafenib; Nivolumab; CapeOX; FOLFOX

Outcome Measures

Primary Outcomes (2)

• Incidence of DLTs in Phase Ib part

  The incidence of DLTs in each cohort will be calculated for the DLT evaluable population.

  4weeks

• ORR in Phase II part

  ORR is defined as the proportion of subjects whose best overall response based on the RECIST guideline version 1.1 is either CR or PR.

  1 year

Secondary Outcomes (5)

• PFS

  1 year

• DoR

  1 year

• DCR

  1 year

• OS

  2 years

• Incidence of adverse events

  up to 30 days after the last dose

Other Outcomes (1)

• Biomarkers in the PhIb and PhII cohort

  1 year

Study Arms (1)

Regorafenib, Nivolumab+CapeOX/FOLFOX

EXPERIMENTAL

Regorafenib and Nivolumab+CapeOX (Cohort A) / Nivolumab+FOLFOX (Cohort B)

Drug: Regorafenib; Drug: Nivolumab; Drug: CapeOX; Drug: FOLFOX regimen

Interventions

Regorafenib DRUG

90 mg administered orally, once daily for 21 consecutive days followed by 7 days off \*Repeat every 4 weeks as Regorafenib therapy

Also known as: Stivarga

Regorafenib, Nivolumab+CapeOX/FOLFOX

Nivolumab DRUG

CohotA:360 mg administered intravenously, every 3 weeks \*Administered on the same day as CapeOX therapy Cohort B: 240 mg administered intravenously, every 2 weeks \*Administered on the same day as FOLFOX therapy

Also known as: Opdivo

Regorafenib, Nivolumab+CapeOX/FOLFOX

CapeOX DRUG

For Cohort A only * Capecitabine 1,000 mg/m\^2 administered orally, twice daily (Days 1 to 14 continuous dosing of CapeOX therapy) * Oxaliplatin 130 mg/m\^2 administered intravenously (Day 1 of CapeOX therapy) \*Repeat every 3 weeks as CapeOX therapy

Also known as: XELOX, Capecitabine and Oxaliplatin

Regorafenib, Nivolumab+CapeOX/FOLFOX

FOLFOX regimen DRUG

For Cohort B only * Leucovorin 400 mg/m\^2 administered intravenously (Day 1 of FOLFOX therapy) * Fluorouracil 400 mg/m\^2 administered intravenously (Day 1 of FOLFOX therapy) and 1,200 mg/m2 administered intravenously (Days 1 to 2 of FOLFOX therapy) * Oxaliplatin 85 mg/m\^2 administered intravenously (Day 1 of FOLFOX therapy) \*Repeat every 2 weeks as FOLFOX therapy

Also known as: Leucovorin, Fluorouracil and Oxaliplatin

Regorafenib, Nivolumab+CapeOX/FOLFOX

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed gastric/ gastroesophageal junction/esophageal adenocarcinoma that is confirmed to be unresectable/recurrent disease
• At least 1 measurable lesion as defined by RECIST guideline version 1.1.
• Age \>= 20 years on the day informed consent is obtained
• ECOG Performance status (PS) 0 or 1
• The most recent laboratory value within 14 days prior to enrollment meets all of the following. (Examinations on the same day of the week 2 weeks prior to the day of enrollment may be utilized.) 1)Neutrophils \>= 1,200/mm\^3 2)Hemoglobin \>= 8.0 g/dL 3)Platelets \>= 75,000/mm\^3 4)Total bilirubin \<= 1.5 mg/dL 5)AST (GOT) \<= 100 IU/L If liver metastases are present: \<= 200 IU/L 6)ALT (GPT) \<= 100 IU/L If liver metastases are present: \<= 200 IU/L 7)Creatinine \<= 1.5 mg/dL 8)Urine protein: any of the following (if any of the test criteria are met, other tests may not be performed.) (i)Urine protein (dipstick) \<= 2+ (ii)Urine protein creatinine (UPC) ratio \< 3.5 (iii)Urine protein \<= 3,500 mg for 24-hour collection sample 9)PT-INR: \<= 1.5 (\<= 3.0 if on an anticoagulant)
• No transfusions within 7 days prior to enrollment. (Transfusions on the same day of the week prior to enrollment are allowed)
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment. Both men and women must agree to use adequate contraception from the time of signing the informed consent form for a period of time (9 months in women and 7 months in men) after the last dose of protocol therapy
• Oral administration is feasible
• Written informed consent to participate in the study has been obtained from the patient themselves

You may not qualify if:

• Prior chemotherapy for unresectable advanced/recurrent gastric/ gastroesophageal junction/esophageal adenocarcinoma (Note: Prior neoadjuvant or adjuvant therapy is allowed. However, treatment must have been completed at least 6 months prior to enrollment and progression must have occurred at least 6 months after the completion of the therapy)
• HER2 positive (IHC3+, or IHC2+ and FISH positive)
• Patients with hypertension that is difficult to control (systolic blood pressure \>= 160 mmHg or diastolic blood pressure \>= 90 mmHg) despite multiple antihypertensive medications
• Patients with a history of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stent placement within 6 months prior to enrollment
• Patients with a history or evidence of congestive heart failure of Class III or higher according to the New York Heart Association (NYHA) classification
• Confirmed metastases to the central nervous system (Confirmation by brain computed tomography scan or magnetic resonance imaging is required at screening only if metastases to the central nervous system are clinically suspected)
• Active double cancers with intensive treatments and possibly affect continuation of protocol treatment
• Those with serious (needing inpatient care) complications (intestinal paralysis, intestinal obstruction, pulmonary fibrosis, poorly controlled diabetes mellitus, cardiac failure, myocardial infarction, angina pectoris, renal failure, hepatic failure, psychiatric disease, cerebrovascular disorder, ulcers requiring blood transfusions, etc.)
• Those with active hepatitis
• HBs antigen positive
• HBs antibody or HBc antibody positive and HBV-DNA positive
• Active hepatitis C (e.g., qualitative detection of HCV RNA) However, those who are HBs antigen positive may be considered eligible if HBV DNA is \<1.3 log IU/mL (\<2.1 log copies/mL) after treatment with antiviral drugs, such as nucleoside analogs.
• Confirmed HIV infection
• Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease. Patients with type 1 diabetes mellitus, hypothyroidism which is manageable by hormone replacement, or skin disorders not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia) are permitted to be enrolled.
• Patients who require treatment with systemic corticosteroids (excluding temporary use for testing or prophylactic administration for allergic reactions, or for reduction of edema associated with radiotherapy), or immunosuppressants, or those treated with any of these therapies within 2 weeks prior to study enrollment

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• Bayer Yakuhin, Ltd.: collaborator

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

regorafenib; Nivolumab; XELOX; Capecitabine; Oxaliplatin; Folfox protocol; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Kohei Shitara, MD

  National Cancer Center Hospital East

  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: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastroenterology and Gastrointestinal Oncology Division

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: May 27, 2022
• Study Start: June 6, 2022
• Primary Completion: April 14, 2024
• Study Completion: August 25, 2025
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)