RegoNivo vs Standard of Care Chemotherapy in AGOC

Summary

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

Conditions

• Gastro-Oesophageal Cancer

Interventions

DRUG

Regorafenib

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

BIOLOGICAL

Nivolumab

human IgG4 monoclonal antibody inhibitor of PD-1

DRUG

Docetaxel

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

DRUG

Paclitaxel

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

DRUG

Irinotecan

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.

DRUG

Trifluridine/Tipracil

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.

Sponsors & Collaborators

• Bayer

  collaborator INDUSTRY

• Bristol-Myers Squibb

  collaborator INDUSTRY

• University of Sydney

  collaborator OTHER

• Academic and Community Cancer Research United

  collaborator OTHER

• Taiwanese Cooperative Oncology Group

  collaborator UNKNOWN

• Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  collaborator UNKNOWN

• National Cancer Center Hospital East

  collaborator OTHER

• Syneos Health

  collaborator OTHER

• Australasian Gastro-Intestinal Trials Group

  lead NETWORK

Principal Investigators

• Nick Pavlakis, Prof · AGITG

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-01

Primary Completion

2025-07-09

Completion

2026-06-01

FDA Drug

Yes

Countries

• United States
• Australia
• Austria
• Germany
• Italy
• Japan
• South Korea
• Spain
• Taiwan

Study Locations