A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer
NCT ID: NCT02773524
Last Updated: 2022-01-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
250 participants
INTERVENTIONAL
2016-11-30
2022-12-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Regorafenib
Regorafenib 160mg (4 x 40 mg tablets) orally, once daily on days 1-21 of each 28 day cycle + best supportive care until progression
Regorafenib
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.
Placebo
Placebo 160mg (4 x 40 mg tablets) orally, once daily on days 1-21 of each 28 day cycle + best supportive care until progression
Placebo
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.
Interventions
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Regorafenib
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.
Placebo
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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.
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. 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.
8. Willing and able to comply with all study requirements, including treatment, timing, and/or nature of required assessments and follow-up.
9. 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).
10. Signed, written informed consent.
Exclusion Criteria
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. Treatment with any previous drug therapy within 2 weeks prior to first dose of study treatment. This includes any investigational therapy.
6. Use of biological response modifiers, such as granulocyte colony stimulating factor (G-CSF), within 3 weeks prior to randomisation.
7. Concurrent treatment with strong CYP3A4 inhibitors or inducers.
8. 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.
9. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization.
10. Arterial thrombotic or ischaemic events, such as cerebrovascular accident, within 6 months prior to randomization.
11. Venous thrombotic events and pulmonary embolism within 3 months prior to randomization.
12. Any haemorrhage or bleeding event ≥ Grade 3 according to CTCAE v4.03 within 4 weeks prior to randomization.
13. Non-healing wound, ulcer, or bone fracture.
14. Interstitial lung disease with ongoing signs and symptoms.
15. 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.
16. 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).
17. 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.
18. 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
19. 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.
20. Serious medical or psychiatric condition(s) that might limit the ability of the patient to comply with the protocol.
21. 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.
18 Years
ALL
No
Sponsors
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Canadian Cancer Trials Group
NETWORK
Academic and Community Cancer Research United
OTHER
National Health and Medical Research Council, Australia
OTHER
Australasian Gastro-Intestinal Trials Group
NETWORK
Responsible Party
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Principal Investigators
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Nick Pavlakis, Prof
Role: STUDY_CHAIR
AGITG
Locations
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Mayo Clinic Arizona
Scottsdale, Arizona, United States
USC Norris
Los Angeles, California, United States
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, United States
Bon Secours Cancer Institute
Midlothian, Virginia, United States
Canberra Hospital
Canberra, Australian Capital Territory, Australia
Border Medical Oncology
Albury, New South Wales, Australia
Monash Medical Centre
Clayton, New South Wales, Australia
Coffs Harbour Health Campus
Coffs Harbour, New South Wales, Australia
Concord Repatriation General Hospital
Concord, New South Wales, Australia
St Vincent's Public Hospital
Darlinghurst, New South Wales, Australia
Gosford Hospital
Gosford, New South Wales, Australia
St George Hospital
Kogarah, New South Wales, Australia
Newcastle Private Hospital
New Lambton Heights, New South Wales, Australia
Port Macquarie Base Hospital
Port Macquarie, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
The Tweed Hospital
Tweed Heads, New South Wales, Australia
Ballarat Oncology and Haematology Services
Wendouree, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Royal Darwin Hospital
Tiwi, Northern Territory, Australia
The Townsville Hospital
Douglas, Queensland, Australia
Royal Brisbane and Womens Hospital
Herston, Queensland, Australia
Sunshine Coast University Hospital
Sunshine Coast, Queensland, Australia
Ashford Cancer Centre Research
Ashford, South Australia, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
St John of God Hospital Subiaco
Subiaco, Western Australia, Australia
PEI Cancer Treatment Centre, Queen Elizabeth Hospital
Charlottetown, , Canada
Queen Elizabeth II Health Sciences Centre
Nova Scotia, , Canada
Ottawa Hospital Research Institute
Ottawa, , Canada
The Research Institute of the McGill University Health Centre
Québec, , Canada
Allan Blair Cancer Centre
Regina, , Canada
Saskatoon Cancer Centre
Saskatoon, , Canada
University Health Network Princess Margaret Cancer Centre
Toronto, , Canada
National Cancer Centre Hospital East
Chiba, Kashiwa, Japan
Hokkaido University Hospital
Sapporo, Kita, Japan
Auckland Hospital
Auckland, , New Zealand
Hallym University Sacred Heart Hospital
Anyang, , South Korea
Dong-A University Hospital
Busan, , South Korea
Chonbuk National University Hospital
Jeonju, , South Korea
Gyeongsang National University Hospital
Jinju, , South Korea
Chung-Ang University Hospital
Seoul, , South Korea
Korea University Anam Hospital
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul National University Bundang Hospital
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
SMG-SNU Boramae Medical Center
Seoul, , South Korea
The Catholic University of Korea - Seoul St. Mary's Hospital
Seoul, , South Korea
The Catholic University of Korea - Yeouido St. Mary's Hospital
Seoul, , South Korea
Yonsei University Health System - Gangnam Severance Hospital
Seoul, , South Korea
Yonsei University Health System - Severance Hospital
Seoul, , South Korea
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, , Taiwan
China Medical University Hospital
Taichung, , Taiwan
National Cheng Kung University Hospital
Taipei, , Taiwan
National Taiwan University Hospital (NTUH)
Taipei, , Taiwan
Taipei Veterans General Hospital (TPVGH)
Taipei, , Taiwan
Countries
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References
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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.
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.
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.
Other Identifiers
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AG0315OG
Identifier Type: -
Identifier Source: org_study_id
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