Ontario Clinical Oncology Group (OCOG)
A multicentre, parallel group, randomized controlled Phase II clinical trial evaluating neoadjuvant Atezolizumab/Bevacizumab versus neoadjuvant SBRT in patients with biopsy proven solitary HCC with PVTT involving the portal vein branches. Both arms are considered experimental, and as such, a Simon two-stage design will be initially used within both arms. Only if both arms are deemed of interest for further study will a comparison between arms, using a pick-the-winner design, be conducted. Following the completion of neoadjuvant therapy, study participants will undergo a CT scan or MRI to assess tumour response to neoadjuvant therapy. Hepatic resection will be performed for those participants who meet the surgical resection criteria.
Hepatocellular Carcinoma
Portal Vein Tumour Thrombosis
Neoadjuvant
Phase 2
Surgical resection without adjuvant therapy is the standard of care for most patients with solitary hepatocellular carcinoma (HCC). The presence of portal vein tumour thrombus (PVTT) is associated with a poor prognosis, and as a result patients usually do not undergo surgery.1 One potential strategy to improve the outcome of patients with HCC and PVTT is to administer treatment to the tumour prior to surgery, i.e. "neoadjuvant" therapy. This strategy has been proven to be effective in other types of cancer, and results in tumour downstaging and potentially eliminates micro-metastatic disease In a recent randomized controlled trial (RCT) in patients with HCC and PVTT, the addition of radiation therapy (RT) to the tumour prior to hepatic surgery was compared with surgery alone.4 There was a statistically significant improvement in survival with RT. Systemic therapy with the tyrosine kinase inhibitor Sorafenib improved survival compared to placebo in patients with advanced HCC and PVTT.5 Another recent trial in patients with advanced HCC demonstrated improved survival with the combination of Atezolizumab, an immune checkpoint inhibitor (ICI), and Bevacizumab, an antibody to vascular endothelial growth factor compared to Sorafenib alone.6 Currently, there is no standard of care for the neoadjuvant treatment of solitary HCC. Radiotherapy has not been widely adopted despite recent evidence suggesting some benefit. It is conceivable that RT will downsize the tumour increasing the surgical resection rate and reducing the shedding of tumour cells. Stereotactic Body Radiation Therapy (SBRT) is a type of RT that provides high dose, focal radiation to tumours using highly precise imaging and treatment fields, with rapid dose fall-off thereby sparing normal tissue. Based on experience in other cancers, it would seem judicious that effective systemic therapy be considered for the neoadjuvant treatment of HCC to downsize the primary tumour and eradicate occult micro-metastases.2,3 We hypothesize that treating patients with HCC and PVTT with either 1) neoadjuvant systemic therapy, or 2) neoadjuvant SBRT may lead to improved hepatic resection rates. Complete hepatic resection is being considered as a surrogate for good long-term outcomes. The aim of our randomized Phase II trial is to select the treatment arm with the most favourable outcomes based on a trade-off between resection rate and toxicity for study in a future trial.}}
Study Type : | Interventional |
Estimated Enrollment : | 70 participants |
Masking : | None (Open Label) |
Primary Purpose : | Treatment |
Official Title : | Neoadjuvant Combination of Atezolizumab/Bevacizumab Versus Neoadjuvant Radiation Therapy Prior to Hepatectomy in Hepatocellular Carcinoma With Portal Vein Tumour Thrombus (ADVANCE HCC) Hoffmann La Roche Protocol Number: ML42525 |
Actual Study Start Date : | October 18, 2022 |
Estimated Primary Completion Date : | June 30, 2026 |
Estimated Study Completion Date : | June 30, 2026 |
Arm | Intervention/treatment |
---|---|
Experimental: Neoadjuvant Atezolizumab/Bevacizumab • Arm 1: neoadjuvant atezolizumab 1200 mg IV q3weeks x 4 cycles, and bevacizumab 15 mg/kg IV q3weeks x 4 cycles |
Combination Product: Neoadjuvant |
Experimental: Neoadjuvant SBRT • Arm 2: neoadjuvant stereotactic body radiation therapy (SBRT), target volume 30 40 Gy, in 6-8 Gy per day over five days, delivered every other day |
Combination Product: Neoadjuvant |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Recruiting
Tom Baker Cancer Centre
Calgary, Alberta, Canada, I love you
Not yet recruiting
Cross Cancer Institute
Edmonton, Alberta, Canada, I will stay away
Recruiting
Juravinski Cancer Centre
Hamilton, Ontario, Canada,
Recruiting
Ottawa Regional Cancer Centre
Ottawa, Ontario, Canada,
Not yet recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, Canada,
Not yet recruiting
8. Research Center of the University of Montreal Hospital Center - CHUM
Montreal, Quebec, Canada,
Not yet recruiting
McGill Cedars Cancer Centre
Montréal, Quebec, Canada,