RegoNivo vs Standard of Care Chemotherapy in AGOC (INTEGRATEIIb)

February 27, 2024 updated by: Australasian Gastro-Intestinal Trials Group

A Randomised Phase III Open Label Study of Regorafenib + Nivolumab vs Standard Chemotherapy in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this international study is to determine if the combination of regorafenib and nivolumab is more effective than standard chemotherapy in prolonging overall survival in a broad group of participants with AGOC, who have progressed after treatment with standard anti-cancer therapy.

In the INTEGRATE study, regorafenib alone was shown to be effective in prolonging the progression-free period in people with AGOC following standard anti-cancer therapy (i.e. it delayed tumour growth), and demonstrated a potential benefit on long term survival. Recent research has shown the early results from this combination of regorafenib & nivolumab may improve outcomes for cancer patients. INTEGRATE IIb will investigate this effect further in a larger group of participants with AGOC.

The study aims to determine:

i. Whether the combination of regorafenib/nivolumab is likely to help patients with AGOC live longer; ii. The effects of this treatment on progression-free survival; iii. The numbers of participants responding to the treatment iv. The effects of this treatment on quality of life v. The side effects and tolerability of this treatment vi. Molecular differences (e.g. variations in genes or proteins) that may account for the effects of this treatment vii. Differences in the costs of care for people on this treatment.

The Investigators plan to enrol 450 participants in the study from, but not limited to; Australia, New Zealand, South Korea, Japan, Taiwan, Canada, USA, Germany, Belgium, Spain, France, Switzerland, Netherlands and Italy.

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Coffs Harbour, New South Wales, Australia, 2450
        • Recruiting
        • Coffs Harbour Health Campus
        • Principal Investigator:
          • Karen Briscoe
        • Contact:
      • Concord, New South Wales, Australia, 2139
        • Recruiting
        • Concord Repatriation General Hospital
        • Contact:
        • Principal Investigator:
          • Kim Tam Bui
      • Darlinghurst, New South Wales, Australia, 2010
        • Recruiting
        • St Vincent's Public Hospital
        • Contact:
        • Principal Investigator:
          • Hao-Wen Sim
      • East Albury, New South Wales, Australia, 2640
        • Recruiting
        • Border Medical Oncology Research Unit
        • Principal Investigator:
          • Craig Underhill
        • Contact:
      • Gosford, New South Wales, Australia, 2250
        • Recruiting
        • Gosford Hospital
        • Principal Investigator:
          • Matthew Wong
        • Contact:
      • Kogarah, New South Wales, Australia, 2217
        • Recruiting
        • St George Hospital
        • Contact:
        • Principal Investigator:
          • Katrin Sjoquist
      • New Lambton Heights, New South Wales, Australia, 2035
        • Recruiting
        • Newcastle Private Hospital
        • Contact:
        • Principal Investigator:
          • Antonino Bonaventura
      • Port Macquarie, New South Wales, Australia, 2444
        • Recruiting
        • Port Macquarie Base Hospital
        • Contact:
        • Principal Investigator:
          • Stephen Begbie
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Prince of Wales Hospital
        • Contact:
        • Principal Investigator:
          • David Goldstein
      • Sydney, New South Wales, Australia, 2065
        • Recruiting
        • Royal North Shore Private Hospital
        • Principal Investigator:
          • Nick Pavlakis
        • Contact:
      • Tweed Heads, New South Wales, Australia, 2485
        • Recruiting
        • The Tweed Hospital
        • Contact:
        • Principal Investigator:
          • Sumit Lumba
      • Wendouree, New South Wales, Australia, 3355
        • Recruiting
        • Ballarat Oncology and Haematology Services
        • Contact:
        • Principal Investigator:
          • George Kannourakis
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital
        • Principal Investigator:
          • Adnan Nagrial
        • Contact:
    • Northern Territory
      • Tiwi, Northern Territory, Australia, 0810
        • Recruiting
        • Royal Darwin Hospital
        • Contact:
        • Principal Investigator:
          • Narayan Karanth
    • Queensland
      • Douglas, Queensland, Australia, 4814
        • Recruiting
        • The Townsville Hospital
        • Contact:
        • Principal Investigator:
          • Nathan Bain
      • Herston, Queensland, Australia, 4029
        • Recruiting
        • Royal Brisbane and Womens Hospital
        • Contact:
        • Principal Investigator:
          • Matthew Burge
      • Sunshine Coast, Queensland, Australia, 4560
        • Recruiting
        • Sunshine Coast University Hospital
        • Contact:
        • Principal Investigator:
          • Alessandra Francesconi
    • South Australia
      • Adelaide, South Australia, Australia, 5011
        • Recruiting
        • The Queen Elizabeth Hospital
        • Principal Investigator:
          • Timothy Price
        • Contact:
      • Bedford Park, South Australia, Australia, 5042
        • Recruiting
        • Flinders Medical Centre
        • Contact:
        • Principal Investigator:
          • Chris Karapetis
    • Tasmania
      • Hobart, Tasmania, Australia, 700
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Monash Health
        • Contact:
        • Principal Investigator:
          • Andrew Strickland
      • Melbourne, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
        • Contact:
        • Principal Investigator:
          • Niall Tebbutt
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Sir Charles Gairdner Hospital
        • Contact:
        • Principal Investigator:
          • Kevin Jasas
      • Subiaco, Western Australia, Australia, 6008
        • Recruiting
        • St John of God Hospital Subiaco
        • Contact:
        • Principal Investigator:
          • Tom Van Hagen
  • Austria
      • Klagenfurt, Austria
        • Recruiting
        • Landeskrankenanstalten-Betriebsgesellschaft-KABEG
        • Principal Investigator:
          • Wolfgang Eisterer
      • Linz, Austria
        • Recruiting
        • Ordensklinikum Linz GmbH Barmherzige Schwestern
        • Principal Investigator:
          • Holger Florian Rumpold
      • Vienna, Austria
        • Not yet recruiting
        • Medizinische Universitaet Wien
        • Principal Investigator:
          • Ayseguel Ilhan-Mutlu
      • Wiener Neustadt, Austria
        • Not yet recruiting
        • Landesklinikum Wiener Neustadt
        • Principal Investigator:
          • Birgit Gruenberger
  • Germany
      • Bad Saarow, Germany
        • Recruiting
        • Helios Bad Saarow
        • Principal Investigator:
          • Daniel Pink
      • Bayreuth, Germany
        • Recruiting
        • Klinikum Bayreuth
        • Principal Investigator:
          • Alexander Kiani
      • Berlin, Germany
        • Recruiting
        • Charite Universitatsmedizin Berlin
        • Principal Investigator:
          • Peter Thuss-Patience
      • Bonn, Germany
        • Recruiting
        • Universitatsklinikum Bonn
        • Principal Investigator:
          • Maria Gonzalez-Carmona
      • Essen, Germany
        • Recruiting
        • KEM/Evang. Kliniken Essen Mitte gGmbH
        • Principal Investigator:
          • Christian Müller
      • Frankfurt, Germany
        • Recruiting
        • Institut für Klinisch Onkol Forschung am Krankenhaus Nordwest
        • Principal Investigator:
          • Thorsten Goetze
      • Greifswald, Germany
        • Not yet recruiting
        • Universitätsklinikum Greifswald
        • Principal Investigator:
          • Ali Aghdassi
      • Hamburg, Germany
        • Recruiting
        • Norddeutsches Studienzentrum für Innovative Onkologie (NIO)
        • Principal Investigator:
          • Eray Gökkurt
      • Heidelberg, Germany
        • Recruiting
        • Universitätsklinikum Heidelberg
        • Principal Investigator:
          • Georg Martin Haag
      • Jena, Germany
        • Recruiting
        • Universitätsklinikum Jena
        • Principal Investigator:
          • Udo Lindig
      • Koeln, Germany
        • Recruiting
        • Kliniken der Stadt Köln
        • Principal Investigator:
          • Stefan Angermeier
      • Leipzig, Germany
        • Recruiting
        • Universitätsklinikum Leipzig
        • Principal Investigator:
          • Gertraud Stocker
      • Leverkusen, Germany
        • Recruiting
        • Klinikum Leverkusen gGmbH
        • Principal Investigator:
          • Andrea Heider
      • Ludwigsburg, Germany
        • Recruiting
        • Klinikum Ludwigburg
        • Principal Investigator:
          • Bernhard Sibbing
      • Magdeburg, Germany
        • Recruiting
        • Klinikum Magdeburg gGmbH
        • Principal Investigator:
          • Christoph Kahl
      • Mainz, Germany
        • Recruiting
        • Universitätsklinikum Mainz
        • Principal Investigator:
          • Markus Möhler
      • Marburg, Germany
        • Recruiting
        • Philipps-Universitat Marburg
        • Principal Investigator:
          • Jorge Riera Knorrenschild
      • München, Germany
        • Recruiting
        • Klinikum rechts der Isar der TU Munchen
        • Principal Investigator:
          • Sylvie Lorenzen
      • Ravensburg, Germany
        • Recruiting
        • Studienzentrum Onkologie Ravensburg
        • Principal Investigator:
          • Tobais Dechow
      • Saarbrücken, Germany
        • Recruiting
        • Caritas Klinikum Saarbrucken St. Theresia
        • Principal Investigator:
          • Manfred P. Lutz
      • Ulm, Germany
        • Recruiting
        • Universitätsklinikum Ulm
        • Principal Investigator:
          • Thomas Ettrich
    • Nordrhein-Westfalen
      • Gütersloh, Nordrhein-Westfalen, Germany
        • Recruiting
        • Evang. Klinikum Bethel Bielefeld
        • Principal Investigator:
          • Kambiz Taghizadeh
  • Italy
      • Napoli, Italy
        • Not yet recruiting
        • Istituto Nazionale Tumori di Napoli-IRCCS Fondazione G. Pascale
        • Principal Investigator:
          • Antonio Avallone
      • Napoli, Italy
        • Not yet recruiting
        • Universitae degli studi della Campania "Luigi Vanvitelli"
        • Principal Investigator:
          • Ferdinando De Vita
      • Reggio Emilia, Italy
        • Recruiting
        • Azienda USL-IRCCS Di Reggio Emilia
        • Principal Investigator:
          • Angela Damato
      • Roma, Italy
        • Not yet recruiting
        • Universita Cattolica del Sacro Cuore, University Hospital Gemelli
        • Principal Investigator:
          • Carmelo Pozzo
      • Roma, Italy
        • Recruiting
        • San Camillo Forlanini Hospitals
        • Principal Investigator:
          • Carlo Garufi
      • San Giovanni Rotondo, Italy
        • Not yet recruiting
        • IRCCS Fondazione Casa Sollievo della Sofferenza
        • Principal Investigator:
          • Evaristo Maiello
  • Japan
      • Fukuoka, Japan
        • Completed
        • Kyushu Cancer Center
      • Matsuyama, Japan
        • Completed
        • Shikoku Cancer Center
      • Saitama, Japan
        • Active, not recruiting
        • Saitama Cancer Center
      • Shizuoka, Japan
        • Active, not recruiting
        • Shizuoka Cancer Center
    • Kashiwa
      • Chiba, Kashiwa, Japan
        • Active, not recruiting
        • National Cancer Centre Hospital East
    • Kita
      • Sapporo, Kita, Japan
        • Active, not recruiting
        • Hokkaido University Hospital
  • Korea, Republic of
      • Anyang, Korea, Republic of
        • Completed
        • Hallym University Sacred Heart Hospital
      • Busan, Korea, Republic of
        • Completed
        • Dong-A University Hospital
      • Busan, Korea, Republic of
        • Active, not recruiting
        • Haeundae Paik Hospital
      • Cheongju, Korea, Republic of
        • Active, not recruiting
        • Chungbuk National University Hospital
      • Jeonju, Korea, Republic of
        • Active, not recruiting
        • Jeonbuk National University Hospital
      • Jinju, Korea, Republic of
        • Completed
        • Gyeongsang National University Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Asan Medical Centre
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Chung-Ang University Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Kangbuk Samsung Hospital
      • Seoul, Korea, Republic of
        • Completed
        • SMG-SNU Boramae Medical Center
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • The Catholic University of Korea - Yeouido St. Mary's Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Yonsei University Health System - Gangnam Severance Hospital
      • Seoul, Korea, Republic of
        • Active, not recruiting
        • Yonsei University Health System - Severance Hospital
      • Seoul, Korea, Republic of
        • Completed
        • The Catholic University of Korea - Seoul St. Mary's Hospital
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Vall d'Hebron University Hospital
        • Principal Investigator:
          • Marc Diez
      • Pamplona, Spain
        • Recruiting
        • Hospital Universitario de Navarra
        • Principal Investigator:
          • Maria Alsina
      • Valencia, Spain
        • Recruiting
        • Hospital Clinico Universitario de Valencia
        • Principal Investigator:
          • Tania Fleitas
  • Taiwan
      • Kaohsiung, Taiwan
        • Recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
        • Principal Investigator:
          • Jaw-Yuan Wang
      • Taichung, Taiwan
        • Recruiting
        • China Medical University Hospital (CMUH)
        • Principal Investigator:
          • Li-Yuan Bai
      • Taipei, Taiwan
        • Recruiting
        • National Cheng Kung University Hospital
        • Principal Investigator:
          • Li-Tzong Chen
      • Taipei, Taiwan
        • Not yet recruiting
        • Taipei Veterans General Hospital (TPVGH)
        • Principal Investigator:
          • Yi-Ping Hung
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital (NTUH)
        • Principal Investigator:
          • Kun-Huei Yeh
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
        • Principal Investigator:
          • Mohamad B. Sonbol
    • California
      • Los Angeles, California, United States, 90001
        • Recruiting
        • USC Norris
        • Principal Investigator:
          • Syma Iqbal
    • Iowa
      • Sioux City, Iowa, United States, 51101
        • Recruiting
        • Siouxland Regional Cancer Center
        • Principal Investigator:
          • Donald Wender
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Recruiting
        • St Elizabeth Healthcare
        • Principal Investigator:
          • Minsig Choi
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Recruiting
        • Monument Health Rapid City Hospital
        • Principal Investigator:
          • Abdel-Ghani Azzouqa
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Centre - South Lake Union Clinic
        • Principal Investigator:
          • David Zhen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer which:

    1. has arisen in any primary gastro-oesophageal site (oesophago-gastric junction (GOJ) or stomach); and
    2. is of adenocarcinoma or undifferentiated carcinoma histology; and
    3. is evaluable according to Response Evaluation Criteria in Solid Tumours (RECIST Version 1.1) by computed tomography (CT) scan performed within 21 days prior to randomisation. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrolment; and
    4. has failed or been intolerant to a minimum of 2 lines of prior anti-cancer therapy for recurrent/metastatic disease which must have included at least one platinum agent and one fluoropyrimidine analogue. Note: Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy will be considered as first line treatment where people have relapsed or progressed within 6 months of completing treatment; Radiosensitising chemotherapy given solely for this purpose concurrent with palliative radiation will not be considered as a line of treatment. Ramucirumab monotherapy, or immunotherapy with a checkpoint inhibitor, will be considered a line of treatment.
    5. HER2-positive participants must have received trastuzumab
  2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 1).
  3. Ability to swallow oral medication.
  4. Adequate bone marrow function (Platelets ≥100x109/L; Absolute Neutrophil Count (ANC) ≥1.5x109/L and Haemoglobin ≥ 9.0g/dL).
  5. Adequate renal function (Creatinine clearance >50 ml/min) based on either the Cockcroft-Gault formula (Appendix 2), 24-hour urine or Glomerular Filtration Rate (GFR) scan; and serum creatinine ≤1.5 x Upper Limit of Normal (ULN).

  6. Adequate liver function (Serum total bilirubin ≤1.5 x ULN, and INR ≤ 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤2.5 x ULN (≤ 5 x ULN for participants with liver metastases)).

    Participants being treated with an anti-coagulant, such as warfarin or heparin, will be allowed to participate provided that no prior evidence of an underlying abnormality in these parameters exists.

  7. Willing and able to comply with all study requirements, including treatment, timing, and/or nature of required assessments and follow-up.
  8. Study treatment both planned and able to start within 7 days after randomisation (note: subjects randomised on a Friday should commence treatment no earlier than the following Monday)
  9. Signed, written informed consent

Exclusion Criteria:

  1. Known allergy to the investigational product drug class or excipients in the regorafenib and/or nivolumab
  2. Poorly-controlled hypertension (systolic blood pressure >140mmHg or diastolic pressure> 90mmHg despite optimal medical management).
  3. Participants with known, uncontrolled malabsorption syndromes
  4. Any prior anti-VEGF targeted therapy using small molecule VEGF TKIs (e.g. apatinib). Prior anti-VEGF targeted monoclonal antibody therapies (e.g. bevacizumab and ramucirumab) are permitted.
  5. Any prior use of more than one immune checkpoint inhibitor
  6. Treatment with any previous drug therapy within 2 weeks prior to first dose of study treatment. This includes any investigational therapy.
  7. Use of biological response modifiers, such as granulocyte colony stimulating factor (G-CSF), within 3 weeks prior to randomisation.
  8. Concurrent treatment with strong CYP3A4 inhibitors or inducers.
  9. Palliative radiotherapy, unless more than 14 days have elapsed between completion of radiation and the date of registration, and adverse events resulting from radiation have resolved to < Grade 2 according to CTCAE V5.0
  10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
  11. Arterial thrombotic or ischaemic events, such as cerebrovascular accident, within 6 months prior to randomization.
  12. Venous thrombotic events and pulmonary embolism within 3 months prior to randomization
  13. Any haemorrhage or bleeding event ≥ Grade 3 according to CTCAE v5.0 within 4 weeks prior to randomization.
  14. Non-healing wound, ulcer, or bone fracture.
  15. Interstitial lung disease with ongoing signs and symptoms
  16. Clinical hyperthyroidism or hypothyroidism. Note: non-clinically significant abnormal TFTs (abnormal TSH and abnormal T3 and/or abnormal T4) considered to be due to sick euthyroid syndrome is allowed.
  17. Persistent proteinuria of ≥ Grade 3 according to CTCAE v5.0 (equivalent to > 3.5g of protein over 24 hour measured on either a random specimen or 24 hour collection.
  18. Uncontrolled metastatic disease to the central nervous system. To be eligible, known CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomization, with no deterioration in neurological symptoms during this time.

  19. History of another malignancy within 2 years prior to randomization. Participants with the following are eligible for this study:

    1. curatively treated cervical carcinoma in situ,
    2. non-melanomatous carcinoma of the skin,
    3. superficial bladder tumours (T1a [Non-invasive tumour], and Tis [Carcinoma in situ]),
    4. treated thyroid papillary cancer
  20. Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy.
  21. Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrolment
  22. Patients with a ≥ grade 3 active infection according to CTCAE version 5.0
  23. Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
  24. Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy; if used as replacement therapy e.g. ≤ 10 mg prednisolone or dexamethasone ≤ 2 mg per day) or immunosuppressants, or who have received such a therapy < 14 days prior to randomisation
  25. Patients with a seizure disorder who require pharmacotherapy
  26. Serious medical or psychiatric condition(s) that might limit the ability of the patient to comply with the protocol.
  27. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to randomization. Men must have been surgically sterilized or use a barrier method of contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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
Other Names:
  • Stivarga
Biological: Nivolumab
human IgG4 monoclonal antibody inhibitor of PD-1
Other Names:
  • Opdivo
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).
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

Other Names:
  • Taxotere
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
Other Names:
  • Abraxane
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.
Other Names:
  • Camptosar
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.
Other Names:
  • Lonsurf

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
O/S
Time Frame: 5 years
To determine the effect of RegoNivo on overall survival (OS) (death from any cause) in the overall study population and in the Asian sub-population.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the effect of RegoNivo on; PFS
Time Frame: 5 years
Progression free survival (PFS)(disease progression or death) in the study population
5 years
Determine the effect of RegoNivo on; OTRR
Time Frame: 5 years
Objective tumour response rate (OTRR)((partial or complete response (PR or CR)) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and iRECIST on study population
5 years
Determine the effect of RegoNivo on; QoL - EORTC Quality of Life Questionnaire
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study EORTC QLQ-C30: Q1 - Q28, Min 1 Max 4, Higher Score = Worse
5 years
Determine the effect of RegoNivo on; QoL - EORTC Quality of Life Questionnaire
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study EORTC QLQ-C30: Q29 & Q30 Min 1 Max 7, Higher = Better
5 years
Determine the effect of RegoNivo on; QoL - EORTC Quality of Life Questionnaire -Stomach Cancer
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study EORTC QLQ STO22 Min 1 Max 4, Higher Score = Worse
5 years
Determine the effect of RegoNivo on; QoL - Patient D.A.T.A form (self assessment of pain on health aspect)
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study Patient D.A.T.A Form: Q1 - Q17 Min 0 Max 10, Higher Score = Worse
5 years
Determine the effect of RegoNivo on; QoL - Patient D.A.T.A form (self rating on health aspects)
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study Patient D.A.T.A Form: Q18 - Q24 Min 0 Max 10, Higher Score = Better
5 years
Determine the effect of RegoNivo on; QoL - Patient D.A.T.A form (health aspect impact self assessment)
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study Patient D.A.T.A Form: Q25 - Q47 Min 0 Max 10, Higher Score = Worse
5 years
Determine the effect of RegoNivo on; QoL - Health Questionnaire
Time Frame: 5 years
Quality of life (QoL)(scores from participant-completed questionnaires) of participants on study EQ-5D-5L Health questionnaire Min 0 Max 100, Higher Score = Better
5 years
Determine the effect of RegoNivo on; Safety
Time Frame: 5 years
Safety (rates of adverse events) of participants on study
5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prognostic biomarker identification for AGOC
Time Frame: Up to 24 months following close of study.
To identify prognostic and predictive biomarkers (tissue and circulating) for study endpoints (relating to survival, response and safety).
Up to 24 months following close of study.
Regorafenib max plasma concentration level assessment (Cmax) across geographical regions
Time Frame: Up to 24 months following close of study.
To evaluate regorafenib Cmax in patient populations from different geographical regions (regorafenib levels).
Up to 24 months following close of study.
Regorafenib levels and correlation to treatment
Time Frame: Up to 24 months following close of study.
To evaluate regorafenib levels and their correlation to outcomes in treatment
Up to 24 months following close of study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Australasian Gastro-Intestinal Trials Group

Collaborators

Bristol-Myers Squibb
Bayer
Syneos Health
University of Sydney
National Cancer Center Hospital East
Academic and Community Cancer Research United
Taiwanese Cooperative Oncology Group
Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Investigators

  • Study Chair: Nick Pavlakis, Prof, AGITG

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

February 24, 2021

First Submitted That Met QC Criteria

May 6, 2021

First Posted (Actual)

May 10, 2021

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 27, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AG0315OG/CTC0140
  • 2020-004617-12 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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