INTEGRATE II

The purpose of INTEGRATE II is to determine whether Regorafenib is effective in prolonging survival in patients with Advanced Gastro-Oesophageal Carcinoma (AGOC).

There currently exist few effective treatment options for patients with Advanced Gastro‐Oesophageal Cancer (AOGC) that has returned after surgery or where it is incurable (metastatic) at diagnosis.  INTEGRATE II is a phase III clinical trial to determine if Regorafenib is an effective new treatment option for patients with advanced gastro-oesophageal cancer.

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Trial Status

Open

Cancer Type

Stomach Cancer

If you think this trial is relevant to your situation, please contact your Cancer Specialist to discuss further.

Aim

The aim of the study is to further examine the findings of the previous INTEGRATE clinical trial.  The purpose of INTEGRATE II is to determine whether Regorafenib is effective in prolonging survival in patients with Advanced Gastro-Oesophageal Carcinoma (AGOC).

Summary

INTEGRATE II is a phase III clinical trial to determine if Regorafenib is an effective new treatment option for patients with advanced gastro-oesophageal cancer. The trial is designed for patients who have metastatic or locally recurrent gastro-oesophageal cancer (in the gastro-oesophageal junction or stomach), which has progressed after conventional treatment.

Treatment options are often limited for patients with advanced stage gastro-oesophageal cancer, especially when the cancer has returned after surgery or if the cancer has become resistant to chemotherapy.

Regorafenib is a medication that targets different signals in the cell responsible for causing the cancer to grow and possibly spread. In a previous clinical trial (INTEGRATE) Regorafenib was found to be effective in suppressing growth of  gastro-oesophageal cancer. Specifically, participants experienced a longer period where their cancer did not grow, and that the drug was no more toxic in participants with AGOC than in patients with other types of cancer. The purpose of INTEGRATE II is to confirm and further examine these results in a larger group of participants. The trial will be conducted over two years.

Regorafenib is taken as an oral tablet daily.

The results from this study have the potential to provide definitive evidence for Regorafenib as a new standard of care after other treatments no longer benefit patients with this type of cancer.

Participating Centres

Australian Capital Territory
Canberra Hospital
New South Wales
Concord Repatriation General Hospital
Gosford Hospital
Newcastle Private Hospital
NCCI – Coffs Harbour Health Campus
Port Macquarie Base Hospital/NCCI
Royal North Shore Hospital
St Vincents Public Hospital
The Tweed Hospital
Westmead Hospital
St George Hospital
Border Medical Oncology
Prince of Wales Hospital
Northern Territory
Royal Darwin Hospital
Queensland
Royal Brisbane and Womens Hospital
Townsville Hospital
Sunshine Coast University Hospital
South Australia
Ashford Cancer Centre
Flinders Medical Centre
Queen Elizabeth Hospital
Tasmania
Royal Hobart Hospital
Victoria
Ballarat Oncology & Haematology Services
Monash Medical Centre
Austin Health
Western Australia
St John of God Hospital, Subiaco
Sir Charles Gairdner Hospital
New Zealand
Auckland City Hospital
Korea
Seoul National University Hospital
Samsung Medical Centre
Yonsei University Health System-Severence Hospital
Korea University Anam Hospital
The Catholic University of Korea-Seoul St Marys Hospital
SMG-SNU Boramae Medical Center
Hallym University Sacred Heart Hospital
Chonbuk National University Hospital
Korea University Guro Hospital
Chung-Ang University Hospital
Taiwan
National Taiwan University Hospital (NTUH)
Taipei Veterans General Hospital (NCKUH)
Kaohsiung Medical University Chung-Ho Memorial Hospital
China Medical University Hospital (CMUH)
Canada
Ottawa Health Research Institute
UHN, Princess Margaret Hospital
Saskatoon Cancer Centre
Allan Blair Cancer Centre
QEII Health Sciences Centre Capital District Health Authority
The Research Institute of the McGill University Health Centre

Trial Status

Open

Cancer Type

Stomach Cancer

If you think this clinical trial may be relevant to your patient or to discuss further, please contact the Clinical Trial team.

Protocol Title

A Randomised Phase III Double-Blind Placebo-Controlled Study of regorafenib in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

Publication Reference

None to date

Conference Presentation Reference

Sjoquist KM, Pavlakis N, Martin AJ, Tsobanis E, Yip S, Bang YJ, Alcindor T, O’Callaghan CJ, Shitara K, Bekaii-Saab TS, Grothey A, Chen LT, Simes J, Zalcberg R, Goldstein D. Integrate II: A randomised phase 3 double-blind placebo-controlled study of regorafenib in refractory advanced gastro-oesophageal cancer—an international study organized by the Australasian Gastrointestinal Trials Group. American Society of Oncology Annual Meeting; 2–6 Jun 2017; Chicago.

Aim

This study follows the success of the Phase II INTEGRATE study, which demonstrated a positive signal with regorafenib. The purpose of INTEGRATE II is to determine whether Regorafenib improves overall survival as a third line therapy in refractory AGOC. The primary objective is overall survival, while secondary objectives include progression free survival, objective response rates, safety, quality of life, and investigation in patient populations from different geographic regions.

Background

INTEGRATE II is a phase III international multi-centre clinical trial to determine whether Regorafenib is effective in prolonging survival in patients with Advanced Gastro-Oesophageal Carcinoma.

The purpose of this clinical trial is to confirm the activity seen in a previous clinical trial (INTEGRATE), which demonstrated the efficacy of Regorafenib in Advanced Gastro-Oesophageal cancer.

Currently, there are few treatment options for patients with advanced gastro-oesophageal carcinoma that has progressed after first and second line chemotherapy.

Regorafenib is being explored as a possible alternative treatment option. Regorafenib is a multi-targeted therapy that targets a number of signals in the cancer cell that cause it to grow and produce blood vessels. Regorafenib has been proven to have a benefit when other drugs have ceased to work in other cancers, such as colon cancer, liver cancer and gastrointestinal stromal tumours (GIST).

CLINICAL TRIAL DESIGN

INTEGRATE II is a randomised phase III, double-blind, controlled trial with 2:1 randomisation with stratification by the location of tumour, geographic region and prior VEGF inhibitors.

Participants in the trial will be randomly allocated to one of two groups: to receive either Regorafenib or a placebo tablet. The Regorafenib/placebo will be taken once per day for the first 21 days, every four weeks.

Participants will be followed up every 2-4 weeks to evaluate how they are responding to treatment. The effectiveness of the treatment will be evaluated by CT scan every 8 weeks.  Throughout the trial the participant’s medical oncologist will determine whether the participant in suitable for ongoing therapy. Treatment will continue until there is cancer progression or adverse events that prohibit the study from progressing.

There will also be follow up with the patient every 2 months to determine survival.

Participants will not know whether they are taking Regorafenib or the placebo until after the trial is completed. It is planned that the trial will be conducted over two years.

Translational studies will also be conducted to see which patients may benefit the most from this treatment. This will be done by detecting certain biomarkers and drug levels in tumour tissue and blood samples of patients who give consent to participate in these studies.

Patients Recruited

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

Open Trial Recruitment Table

Participating Centres

Australian Capital Territory
Canberra Hospital
New South Wales
Concord Repatriation General Hospital
Gosford Hospital
Newcastle Private Hospital
NCCI – Coffs Harbour Health Campus
Port Macquarie Base Hospital/NCCI
Royal North Shore Hospital
St Vincents Public Hospital
The Tweed Hospital
Westmead Hospital
St George Hospital
Border Medical Oncology
Prince of Wales Hospital
Northern Territory
Royal Darwin Hospital
Queensland
Royal Brisbane and Womens Hospital
Townsville Hospital
Sunshine Coast University Hospital
South Australia
Ashford Cancer Centre
Flinders Medical Centre
Queen Elizabeth Hospital
Tasmania
Royal Hobart Hospital
Victoria
Ballarat Oncology & Haematology Services
Monash Medical Centre
Austin Health
Western Australia
St John of God Hospital, Subiaco
Sir Charles Gairdner Hospital
New Zealand
Auckland City Hospital
Korea
Seoul National University Hospital
Samsung Medical Centre
Yonsei University Health System-Severence Hospital
Korea University Anam Hospital
The Catholic University of Korea-Seoul St Marys Hospital
SMG-SNU Boramae Medical Center
Hallym University Sacred Heart Hospital
Chonbuk National University Hospital
Korea University Guro Hospital
Chung-Ang University Hospital
Taiwan
National Taiwan University Hospital (NTUH)
Taipei Veterans General Hospital (NCKUH)
Kaohsiung Medical University Chung-Ho Memorial Hospital
China Medical University Hospital (CMUH)
Canada
Ottawa Health Research Institute
UHN, Princess Margaret Hospital
Saskatoon Cancer Centre
Allan Blair Cancer Centre
QEII Health Sciences Centre Capital District Health Authority
The Research Institute of the McGill University Health Centre

Key Eligibility Criteria

Please note that the information below contains only the most important inclusion and exclusion criteria and is not a comprehensive list.

Key inclusion criteria:

  • Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer
  • Patients who have failed or have been intolerant to 2 prior courses of chemotherapy for advanced gastro-oesophageal cancer
  • Ability to swallow oral medication
  • Adequate kidney, bone marrow, renal, liver and cardiac function

Key exclusion criteria:

  • Known allergy to Regorafenib or its excipients
  • Patients with significant active infection, which include chronic active hepatitis B, C or HIV
  • Poorly controlled hypertension (blood pressure)
  • Known uncontrolled malabsorption syndromes
  • Had treatment with any drug therapies within the 28 days prior to randomisation
  • Patients who have had major surgery, open biopsy or major traumatic injury within the 28 days prior to randomisation
  • Pregnancy.

Visit ANZTCR for more detailed information on inclusion/exclusion criteria and eligibility.

Study Chairs

Associate Nick Pavlakis (Royal North Shore Hospital, Sydney)
Conjoint Professor David Goldstein (Prince of Wales Hospital, Sydney)

Principal Investigator

Associate Professor Nick Pavlakis

Detailed Information Available on

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

Funding

Bayer HealthCare Pharmaceuticals Inc