5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).

Background

For selected patients with oligometastatic colorectal cancer (mCRC), local treatment of metastases is standard of care based on retrospective reports showing long term survival rates. Local treatment of metastases is technically feasible in an increasing number of patients with multi-organ mCRC. It is unknown whether patients with extensive disease will benefit from tumor debulking when added to first line palliative chemotherapy.

The aim of the ORCHESTRA trial (NCT01792934) is to improve overall survival (OS) with at least six months by maximal tumor debulking in combination with systemic therapy in patients with multi-organ mCRC.

Trial design

Patients with multi-organ mCRC are eligible if ≥ 80% tumor debulking is deemed feasible by resection, radiotherapy and/or thermal ablative therapy. All patients receive 5FU and oxaliplatin based chemotherapy ± bevacizumab. In case of response or stable disease at first evaluation (+/- 2 months), patients are randomized to continuation of chemotherapy or maximal tumor debulking followed by continuation of chemotherapy. A total of 478 patients will be included to meet the primary endpoint (≥ 6 months OS benefit, power 80%, 5% type I error rate two sided). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Quality of life is an important secondary endpoint of the trial. Tissue and blood specimen are collected for translational research. Currently, 290 patients are included in 27 participating Dutch hospitals. Several centers in the United Kingdom will soon participate in the trial.

Clinical trial identification

NCT01792934.

Editorial acknowledgement

Legal entity responsible for the study

Amsterdam University Medical Center, Location VUmc.

Funding

The ORCHESTRA trial is financially supported by KWF (Dutch Cancer Foundation), Blokker-Verwer foundation and Roche.

Disclosure

All authors have declared no conflicts of interest.