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Gastro-Oesophageal CancerPhase 3INTEGRATEIIaNCT02773524

A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer

A Phase 3 study testing Regorafenib in people with Gastro-Oesophageal Cancer, run by Australasian Gastro-Intestinal Trials Group at 60 sites in 7 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

A randomised phase III, double-blind, placebo-controlled trial with 2:1 (regorafenib : placebo) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastro-Oesophageal Cancer
What is being tested?
Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
250 participants
Where
60 sitesin 7 countries
Study dates
Nov 2016to Dec 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer which:
  • has arisen in any primary gastro-oesophageal site (oesophago-gastric junction (GOJ) or stomach); and
  • is of adenocarcinoma or undifferentiated carcinoma histology , and
  • 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
  • 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.
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  • HER2-positive participants must have received trastuzumab.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Ability to swallow oral medication.
  • Adequate bone marrow function (Platelets ≥100x109/L; Absolute Neutrophil Count (ANC) ≥1.5x109/L and Haemoglobin ≥ 9.0g/dL).
  • 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).
  • 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.
  • Adequate cardiac function (Left Ventricular Ejection Fraction (LVEF) ≥ 50% or above the lower limit of normal (LLN) for the Institution (whichever is lower). Cardiac function should be assessed within 3 months prior to randomisation, but after completion of any anthracycline-containing chemotherapy.
  • Willing and able to comply with all study requirements, including treatment, timing, and/or nature of required assessments and follow-up.
  • 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).
  • Signed, written informed consent.

Who cannot join

  • Known allergy to the investigational product drug class or excipients in the regorafenib.
  • Poorly-controlled hypertension (systolic blood pressure >140mmHg or diastolic pressure> 90mmHg despite optimal medical management).
  • Participants with known, uncontrolled malabsorption syndromes.
  • 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.
  • Treatment with any previous drug therapy within 2 weeks prior to first dose of study treatment. This includes any investigational therapy.
  • Use of biological response modifiers, such as granulocyte colony stimulating factor (G-CSF), within 3 weeks prior to randomisation.
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  • Concurrent treatment with strong CYP3A4 inhibitors or inducers.
  • 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 V4.03.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization.
  • Arterial thrombotic or ischaemic events, such as cerebrovascular accident, within 6 months prior to randomization.
  • Venous thrombotic events and pulmonary embolism within 3 months prior to randomization.
  • Any haemorrhage or bleeding event ≥ Grade 3 according to CTCAE v4.03 within 4 weeks prior to randomization.
  • Non-healing wound, ulcer, or bone fracture.
  • Interstitial lung disease with ongoing signs and symptoms.
  • 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.
  • Persistent proteinuria of ≥ Grade 3 according to CTCAE v4.03 (equivalent to > 3.5g of protein over 24 hours, measured on either a random specimen or 24 hour collection).
  • Uncontrolled metastatic disease to the central nervous system. To be eligible, 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.
  • History of another malignancy within 2 years prior to randomization. Participants with the following are eligible for this study:
  • curatively treated cervical carcinoma in situ,
  • non-melanomatous carcinoma of the skin,
  • superficial bladder tumours (T1a [Non-invasive tumour], and Tis[Carcinoma in situ]),
  • treated thyroid papillary cancer
  • 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.
  • Serious medical or psychiatric condition(s) that might limit the ability of the patient to comply with the protocol.
  • 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.

Trial locations and contacts

60 sites in 7 countries.

60 sites in 7 countries

Australia26 sites

  • Border Medical Oncology

    Albury, New South Wales, 2640

  • Ashford Cancer Centre Research

    Ashford, South Australia, 5035

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Canberra Hospital

    Canberra, Australian Capital Territory

  • Monash Medical Centre

    Clayton, New South Wales, 3168

  • Coffs Harbour Health Campus

    Coffs Harbour, New South Wales, 2450

  • Concord Repatriation General Hospital

    Concord, New South Wales, 2139

  • St Vincent's Public Hospital

    Darlinghurst, New South Wales, 2010

  • The Townsville Hospital

    Douglas, Queensland, 4814

  • Gosford Hospital

    Gosford, New South Wales, 2250

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Brisbane and Womens Hospital

    Herston, Queensland, 4029

  • Royal Hobart Hospital

    Hobart, Tasmania, 700

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Newcastle Private Hospital

    New Lambton Heights, New South Wales, 2035

  • Port Macquarie Base Hospital

    Port Macquarie, New South Wales, 2444

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Royal North Shore Hospital

    Saint Leonards, New South Wales

  • St John of God Hospital Subiaco

    Subiaco, Western Australia, 6008

  • Sunshine Coast University Hospital

    Sunshine Coast, Queensland, 4560

  • Royal Darwin Hospital

    Tiwi, Northern Territory, 0810

  • The Tweed Hospital

    Tweed Heads, New South Wales, 2485

  • Ballarat Oncology and Haematology Services

    Wendouree, New South Wales, 3355

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

South Korea15 sites

  • Hallym University Sacred Heart Hospital

    Anyang

  • Dong-A University Hospital

    Busan

  • Chonbuk National University Hospital

    Jeonju

  • Gyeongsang National University Hospital

    Jinju

  • Chung-Ang University Hospital

    Seoul

  • Korea University Anam Hospital

    Seoul

  • Korea University Guro Hospital

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Bundang Hospital

    Seoul

  • Seoul National University Hospital

    Seoul

  • SMG-SNU Boramae Medical Center

    Seoul

  • The Catholic University of Korea - Seoul St. Mary's Hospital

    Seoul

  • The Catholic University of Korea - Yeouido St. Mary's Hospital

    Seoul

  • Yonsei University Health System - Gangnam Severance Hospital

    Seoul

  • Yonsei University Health System - Severance Hospital

    Seoul

Other trials in South Korea

Canada7 sites

  • PEI Cancer Treatment Centre, Queen Elizabeth Hospital

    Charlottetown

  • Queen Elizabeth II Health Sciences Centre

    Nova Scotia

  • Ottawa Hospital Research Institute

    Ottawa

  • The Research Institute of the McGill University Health Centre

    Québec

  • Allan Blair Cancer Centre

    Regina

  • Saskatoon Cancer Centre

    Saskatoon

  • University Health Network Princess Margaret Cancer Centre

    Toronto

Other trials in Canada

Taiwan5 sites

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • National Cheng Kung University Hospital

    Taipei

  • National Taiwan University Hospital (NTUH)

    Taipei

  • Taipei Veterans General Hospital (TPVGH)

    Taipei

Other trials in Taiwan

United States4 sites

  • USC Norris

    Los Angeles, California, 90001

  • Bon Secours Cancer Institute

    Midlothian, Virginia, 76065

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85054

  • Carle Cancer Center NCI Community Oncology Research Program

    Urbana, Illinois, 61801

Other trials in United States

Japan2 sites

  • National Cancer Centre Hospital East

    Chiba, Kashiwa

  • Hokkaido University Hospital

    Sapporo, Kita

Other trials in Japan

New Zealand1 site

  • Auckland Hospital

    Auckland, 1023

Other trials in New Zealand

About this study

Official title: A Randomised Phase III Double-Blind Placebo-Controlled Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

A randomised phase III, double-blind, placebo-controlled trial with 2:1 (regorafenib : placebo)

Read the detailed description

Purpose:

The purpose of this Phase III study is to determine if regorafenib improves overall survival in patients with Advanced Gastro-Oesophageal Carcinoma.

Who is it for:

You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with advanced (metastatic or locally recurrent) Gastro-Oesophageal Carcinoma which has not responded to a minimum of 2 lines of prior anti-cancer therapy.

Trial Details:

Participants will be randomly (by chance) allocated to one of two groups: regorafenib or placebo in 2:1 ratio respectively and will not be aware of their group allocation. Regorafenib or matching placebo will be self-administered by participants orally once daily on days 1-21 of each 28 days cycle. Treatment will continue until disease progression or prohibitive toxicity. Participants will be followed up every 2-4 weeks in order to evaluate their progress on the study.

Being tested
Regorafenib, Placebo
Keywords
Metastatic, Locally recurrent, Oesophago-gastric junction, Stomach, Adenocarcinoma, Undifferentiated Carcinoma
Medical subject headings
Neoplasm Metastasis, Adenocarcinoma, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RegorafenibDrug

    Also called Stivarga

    Regorafenib is the experimental intervention in this study. Regorafenib will be self-administered by participants at 160mg (4 x 40mg tablets) orally once daily on days 1-21 of each 28 day cycle plus best supportive care until progression or prohibitive toxicity as defined by the protocol.

  • PlaceboOther

    Placebo (matching in appearance to regorafenib) made of microcrystalline cellulose, will be self-administered by participants at 160mg (4 x 40mg tablets) orally once daily on days 1-21 of each 28 day cycle plus best supportive care until progression or prohibitive toxicity as defined by the protocol.

Study groups in NCT02773524
Study groupRoleWhat they receive
RegorafenibExperimentalRegorafenib 160mg (4 x 40 mg tablets) orally, once daily on days 1-21 of each 28 day cycle + best supportive care until progression
Receives: Drug: Regorafenib
PlaceboPlacebo comparatorPlacebo 160mg (4 x 40 mg tablets) orally, once daily on days 1-21 of each 28 day cycle + best supportive care until progression
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    The interval from the date of randomisation to date of death from any cause, or the date last known alive.

    Measured: From time of patient randomisation until date last known alive (up to 12 months following end of treatment).

Secondary outcomes (4)

  1. Progression Free Survival

    The interval from the date of randomisation to the date of first evidence of disease progression or death, whichever occurs first.

    Measured: From time of patient randomisation until first evidence of disease progression or death (up to 12 months following randomisation).

  2. Objective Tumour Response Rate

    The OTRR will be calculated by summing the number of participants in a given arm that are assessed as having a complete or partial response (as per RECIST criteria), and dividing this by the total number of participants in the corresponding arm of the analysis set.

    Measured: From time of patient randomisation until evidence of complete or partial response (up to 12 months following randomisation).

  3. Evaluation of health states experienced by participants

    Questionnaire used to assess quality of life

    Measured: From time of commencement of treatment until first evidence of disease progression (up to 12 months following commencement of treatment).

  4. Rates of Adverse Events

    A descriptive analysis of the adverse events (AE) data will be prepared for participants in the safety population. The number and percentage of participants who experience AEs will be tabulated according to CTCAE term/category, grade, and seriousness.

    Measured: From time dose of study treatment until 30 days after last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionJan 2022 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
250 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02773524
Sponsor's protocol ID
AG0315OG
Acronym
INTEGRATEIIa
Status last verified
Jan 2022
First submitted
4 May 2016
Last updated
13 Jan 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • Soon YY, Sjoquist K, Marschner IC, Schou IM, Pavlakis N, Goldstein D, Shitara K, Stockler MR, Simes J, Martin AJ. INTEGRATE pooled phase 2/3 results are robust to postprogression switching and the winner's curse. JNCI Cancer Spectr. 2025 Jul 1;9(4):pkaf053. doi: 10.1093/jncics/pkaf053.

    PubMed 40455046

  • Pavlakis N, Shitara K, Sjoquist K, Martin A, Jaworski A, Tebbutt N, Bang YJ, Alcindor T, O'Callaghan C, Strickland A, Rha SY, Lee KW, Kim JS, Bai LY, Hara H, Oh DY, Yip S, Zalcberg J, Price T, Simes J, Goldstein D. INTEGRATE IIa Phase III Study: Regorafenib for Refractory Advanced Gastric Cancer. J Clin Oncol. 2025 Feb;43(4):453-463. doi: 10.1200/JCO.24.00055. Epub 2024 Oct 4.

    PubMed 39365958

  • Lam LL, Pavlakis N, Shitara K, Sjoquist KM, Martin AJ, Yip S, Kang YK, Bang YJ, Chen LT, Moehler M, Bekaii-Saab T, Alcindor T, O'Callaghan CJ, Tebbutt NC, Hague W, Chan H, Rha SY, Lee KW, Gebski V, Jaworski A, Zalcberg J, Price T, Simes J, Goldstein D. INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG). BMC Cancer. 2023 Feb 22;23(1):180. doi: 10.1186/s12885-023-10642-7.

    PubMed 36814222

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Regorafenib in people with Gastro-Oesophageal Cancer, run by Australasian Gastro-Intestinal Trials Group at 60 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in Australia, South Korea, Canada, Taiwan, United States and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: From time of patient randomisation until date last known alive (up to 12 months following end of treatment).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02773524, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2022.

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