A Randomised Phase II Double-Blind Study of Regorafenib or Placebo in Refractory Advanced Oesophago-Gastric Cancer (AOGC)
- Conditions
- Advanced (metastatic or locally recurrent) oesophago-gastric cancer.Cancer - Oesophageal (gullet)Cancer - Stomach
- Registration Number
- ACTRN12612000239864
- Lead Sponsor
- The Australasian Gastro-Intestinal Trials Group (AGITG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 150
1.Adults (18 years or over) with metastatic or locally recurrent oesophago-gastric cancer which:
i)has arisen in any primary oesophago-gastric site (oesophago-gastric junction (OGJ) or stomach); and
ii)is of adenocarcinoma or undifferentiated carcinoma histology, and
iii)is measurable according to Response Evaluation Criteria in Solid Tumours (RECIST Version 1.1) criteria 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
iv)has been treated with a maximum of 2 lines of chemotherapy for recurrent/metastatic disease; to be eligibile all participants should have received or been intolerant of one or more platinum agents and one or more fluoropyrimidine analogues.
Note: Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy will be considered as first line treatment where people have relapsed or progessed 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.
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 Neurophil Count (ANC) >=1.5x109/L and Haemoglobin >= 9.0g/dL).
5.Adequate renal function (Creatinine clearance >50 ml/min based on the Cockcroft-Gault formula, 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, 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 of randomisation.
10.Signed, written informed consent.
1.Known allergy to the investigational product drug class or excipients in the regorafenib formulation.
2.Poorly controlled hypertension (systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
3.Participants with known malabsorption syndromes.
4.Any prior anti-VEGF targeted therapy (e.g. bevacizumab) or treatment with small molecule VEGF TKIs.
5.Treatment with any investigational agent within 4 weeks prior to randomisation. For the purposes of this study trastuzumab is not considered an investigational agent.
6.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 V4.0.
7.Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before prior to randomisation.
8.Arterial thrombotic or ischaemic events, such as cerebrovascular accident or pulmonary embolism within 6 months prior to randomisation.
9.Venous thrombotic events within 3 months prior to randomisation.
10. Any hemorrhage or bleeding event CTCAE V4.0 >= Grade 3 within 4 weeks prior to the date of randomisation.
11.Non-healing wound, ulcer, or bone fracture.
12.Interstitial lung disease with ongoing signs and symptoms.
13.Life expectancy of less than 12 weeks.
14.Abnormal thyroid function (TSH outside normal range).
15.Persistent proteinuria of CTCAE V4.0 >= Grade 3 (>3.5g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample).
16.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, with no deterioration in neurological symptoms during this time.
17.History of another malignancy within 5 years prior to randomisation. Participants with curatively treated cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or superficial bladder tumours (T1a [Non-invasive tumor], and Tis [Carcinoma in situ]), or participants who have been free of other malignancies for >= 5 years prior to randomisation are eligible for this study.
18.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.
19.Serious medical or psychiatric condition(s) that might limit the ability of the patient to comply with the protocol.
20.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 randomisation. Men must have been surgically sterilised or use a barrier method of contraception.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate progression free survival (disease progression or death)[Tumour response will be assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines via CT scan within 21 days prior to randomisation, and then every 4 weeks for the first 12 weeks and then every 6 weeks for a further 12 weeks and then every 8 weeks thereafter until disease progression.]
- Secondary Outcome Measures
Name Time Method