INTEGRATE IIb

Protocol Title

INTEGRATE II: Randomised Phase III Controlled Trials of Regorafenib containing regimens versus standard care in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

Purpose of the Study

Advanced Gastro-oesophageal Carcinoma (AGOC) has a poor prognosis, and there is no established standard treatment following failure of first- and second-line chemotherapy. Regorafenib is an investigational oral multi-targeted inhibitor. Regorafenib was shown to prolong progression free survival in INTEGRATE.  The INTEGRATE II trial is currently a randomised phase III, controlled trial aiming to determine if regorafenib improves overall survival in refractory AGOC.

With the shift in practice in AGOC resulting in use of multiple lines of therapy, the use of new immunotherapy agents, and the promising activity of RegoNivo, this amended trial is proposed to compare the effectiveness of RegoNivo in pre-treated patients with AGOC to the current standard therapy.

The aim of INTEGRATE IIb is to determine if the regorafenib and nivolumab combination (RegoNivo) improves overall survival compared with current standard chemotherapy options in refractory AGOC.

Eligibility Criteria

Inclusion Criteria

• 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.
  • 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
• Adequate renal function
• 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
• 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
• Participants with known, uncontrolled malabsorption syndromes
• Treatment with any previous drug therapy within 2 weeks prior to first dose of study treatment. This includes any investigational therapy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
• Interstitial lung disease with ongoing signs and symptoms
• Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV.
• Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
• 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.

Contact Email

INTEGRATEII@ctc.usyd.edu.au

Study Chairs

Professor Nick Pavlakis
Professor Kohei Shitara
Professor David Goldstein

DETAILED INFORMATION AVAILABLE

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) please click here

Funding

Bayer HealthCare Pharmaceuticals Inc

Patients Recruited

Click here to access the table and view recruitment data on all AGITG open trials:

Open Trial Recruitment Table