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Study type
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Identifiers
About
To determine if the regorafenib and nivolumab combination (RegoNivo) improves overall survival compared with current standard chemotherapy options in refractory AGOC.
Full 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 460 participants in the study from, but not limited to; Australia, South Korea, Japan, Taiwan, USA, Germany, Austria, Spain, and Italy.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer which:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 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.
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
Exclusion criteria
Known allergy to the investigational product drug class or excipients in the regorafenib and/or nivolumab
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.
Any prior use of more than one immune checkpoint inhibitor
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.
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 V5.0
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 v5.0 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 v5.0 (equivalent to > 3.5g of protein over 24 hour measured on either a random specimen or 24 hour collection.
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.
History of another malignancy within 2 years prior to randomization. Participants with the following are eligible for this study:
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.
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
Patients with a ≥ grade 3 active infection according to CTCAE version 5.0
Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
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
Patients with a seizure disorder who require pharmacotherapy
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.
Primary purpose
Allocation
Interventional model
Masking
450 participants in 2 patient groups
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Central trial contact
Clinical Project Manager
Data sourced from clinicaltrials.gov
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