RegoNivo vs Standard of Care Chemotherapy in AGOC

Conditions

• Gastro-Oesophageal Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Regorafenib — DRUG
  Oral multi-targeted tyrosine kinase inhibitor (TKI) which targets angiogenic (VEGF, TIE-2), stromal (PDGF-β), and oncogenic (RAF, RET and KIT) receptor tyrosine kinases
• Nivolumab — BIOLOGICAL
  human IgG4 monoclonal antibody inhibitor of PD-1
• Docetaxel — DRUG
  Docetaxel is taxane-derivative chemotherapy drug, used in the treatment of early, locally advanced and metastatic breast cancer. It is an anti-microtubule agent. Other uses are in the treatment of non-small cell lung cancer, advanced stomach cancer, head and neck cancers, soft tissue sarcoma, ovarian cancer, metastatic prostate cancer, etc. microtubules, and simultaneously promotes assembly and inhibits disassembly of them
• Paclitaxel — DRUG
  Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs, such as colchicine, that inhibit microtubule assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks the progression of mitosis and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G0-phase of the cell cycle without cell division
• Irinotecan — DRUG
  Camptothecin, one of the four major structural classifications of plant-derived anti-cancerous compounds, is a cytotoxic alkaloid which consists of a pentacyclic ring structure containing a pyrrole (3, 4 β) quinoline moiety, an S-configured lactone form, and a carboxylate form. Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.
• Trifluridine/Tipracil — DRUG
  The drug consists of the cytotoxin trifluridine and the thymidine phosphorylase inhibitor (TPI) tipiracil. Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth. Trifluridine (TFT) is incorporated into DNA by phosphorylation by thymidylate kinase (TK) to TF-TMP; TF-TMP then covalently binds to tyrosine 146 of the active site of thymidylate synthase (TS) inhibiting the enzyme's activity. TS is vital to the synthesis of DNA because it is an enzyme involved in the synthesis of the deoxynucleotide, thymidine triphosphate (dTTP). Inhibition of TS depletes the cell of dTTP and causes accumulation of deoxyuridine monophosphate (dUMP), which increases the likelihood that uracil gets misincorporated into the DNA.

Study Details

To determine if the regorafenib and nivolumab combination (RegoNivo) improves overall survival compared with current standard chemotherapy options in refractory AGOC.

Key Dates

Start date

May 5, 2021

Status verified

Jun 2026

Primary completion

Jan 14, 2025

Completion

Apr 30, 2025

Study Design

Enrollment

462 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: RegoNivo
  Participants in the RegoNivo arm will; 1. self-administer 90mg (3x30mg) of regorafenib days 1-21 of each 28-day treatment cycle and; 2. receive intravenous nivolumab 240 mg day 1 of each 14 day cycle until disease progression or prohibitive adverse events as per protocol, given in hospital by infusion. After 2 months, patients whose disease is controlled may have nivolumab administered 480 mg every 28 days.
• Active Comparator: Standard of Care
  Participants in the control arm will receive investigator choice chemotherapy with any of the following agents * taxane (paclitaxel or docetaxel) * irinotecan or * oral trifluridine/tipiracil (TAS102) All treatment groups will receive Best Supportive Care (BSC).

Primary Outcome Measure

O/S [ Time Frame: From the date of randomisation to date of death from any cause or the date last known alive, assessed up to approximately 44 months. ]

Locations (6)

Related coverage on Hipa.ai

• Nivolumab (RegoNivo) Misses OS Endpoint in Advanced Gastro-Oesophageal Cancer
  Nivolumab · Jun 10, 2026 · ClinicalTrials.gov
• Nivolumab Phase 3 Trial in Gastro-Oesophageal Cancer Reaches Primary Completion
  Nivolumab · Jul 9, 2025 · ClinicalTrials.gov
• Nivolumab Combination Fails to Improve OS in Gastro-Oesophageal Cancer
  Nivolumab · Jan 14, 2025 · ClinicalTrials.gov

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