Clinical Trials /

A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer

NCT02773524

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Undifferentiated Gastric Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AG0315OG
  • NCT ID: NCT02773524

Conditions

  • Gastro-Oesophageal Cancer

Interventions

DrugSynonymsArms
RegorafenibRegorafenib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RegorafenibExperimentalRegorafenib 160mg (4 x 40 mg tablets) orally, once daily on days 1-21 of each 28 day cycle + best supportive care until progression
  • 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

    Eligibility Criteria

            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.
    
              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
    
              1. Known allergy to the investigational product drug class or excipients in the
                 regorafenib.
    
              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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival
    Time Frame:From time of patient randomisation until date last known alive (up to 12 months following end of treatment).
    Safety Issue:
    Description:The interval from the date of randomisation to date of death from any cause, or the date last known alive.

    Secondary Outcome Measures

    Measure:Progression Free Survival
    Time Frame:From time of patient randomisation until first evidence of disease progression or death (up to 12 months following randomisation).
    Safety Issue:
    Description:The interval from the date of randomisation to the date of first evidence of disease progression or death, whichever occurs first.
    Measure:Objective Tumour Response Rate
    Time Frame:From time of patient randomisation until evidence of complete or partial response (up to 12 months following randomisation).
    Safety Issue:
    Description: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.
    Measure:Evaluation of health states experienced by participants
    Time Frame:From time of commencement of treatment until first evidence of disease progression (up to 12 months following commencement of treatment).
    Safety Issue:
    Description:Questionnaire used to assess quality of life
    Measure:Rates of Adverse Events
    Time Frame:From time dose of study treatment until 30 days after last dose of study treatment
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Australasian Gastro-Intestinal Trials Group

    Trial Keywords

    • Metastatic
    • Locally recurrent
    • Oesophago-gastric junction
    • Stomach
    • Adenocarcinoma
    • Undifferentiated Carcinoma

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