Neoadjuvant Combination of Atezolizumab/Bevacizumab Versus Neoadjuvant Radiation Therapy

NCT05137899 | Terminated Phase 2 DMC

• 1 other identifier: OCOG-2021-ADVANCE HCC ML42545
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; Portal Vein Tumour Thrombosis

Keywords

Neoadjuvant Atezolizumab/Bevacizumab; Neoadjuvant Stereotactic Body Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• Hepatectomy

  Proportion of patients who undergo hepatectomy in each arm (number of patients who undergo hepatectomy divided by the number of patients randomized to each arm).

  17 Weeks

Secondary Outcomes (6)

• Response rate

  2 years

• Toxicity to SBRT

  2 years

• Postoperative complications

  90 days post operatively

• Survival Progression Free

  2 years

• Survival

  2 years

Study Arms (2)

Neoadjuvant Atezolizumab/Bevacizumab

EXPERIMENTAL

• Arm 1: neoadjuvant atezolizumab 1200 mg IV q3weeks x 4 cycles, and bevacizumab 15 mg/kg IV q3weeks x 4 cycles

Combination Product: Neoadjuvant

Neoadjuvant SBRT

EXPERIMENTAL

• 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

Interventions

Neoadjuvant COMBINATION_PRODUCT

Neoadjuvant atezolizumab/bevacizumab or neoadjuvant SBRT prior to hepatectomy

Neoadjuvant Atezolizumab/Bevacizumab; Neoadjuvant SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proven solitary HCC without biliary invasion, or metastases,
• PVTT involving the portal vein branches: Vp1-Vp3 (Japanese Classification for HCC with PVTT, see Appendix II),
• \<10 cm maximal diameter on CT or MRI,
• Child-Pugh Class A (see Appendix III), within 14 days prior to randomization. (All parameters without transfusion within 3 months).
• Age \> 18 years.

You may not qualify if:

• Abnormal laboratory parameters (within 14 days of randomization):
• Hemoglobin \< 90 g/L
• Platelet count \< 75 x 109/L without transfusion
• INR \>1.25
• Serum creatinine \> 1.5 x ULN
• Urine dipstick for proteinuria \> 2 (unless a 24-hour urine collection demonstrates \< 1.5 g of protein in 24 hours.
• Previous therapy for HCC:
• Systemic therapy, surgery or radiation therapy,
• Local therapy to the liver (e.g., ablation or embolization) within 28 days prior to randomization.
• ECOG performance status \> 2 (see Appendix IV).
• Non-healing wound, skin ulcers, or incompletely healed bone fracture.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy.
• History of bleeding from esophageal and/or gastric varices or high risk of bleeding from varices seen on endoscopy (normal EGD required within 6 months of randomization).
• History of GI perforation, abdominal fistulae, or intra-abdominal abscess.
• Significant cardiovascular disease:

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Hoffmann-La Roche: collaborator

Study Sites (7)

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V5C2, Canada

Location

Ottawa Regional Cancer Centre

Ottawa, Ontario, K1H8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

8. Centre the recherche du Centre hospitalier de l'Université de Montréal - CHUM

Montreal, Quebec, Canada

Location

McGill Cedars Cancer Centre

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Brandon Meyers, MD

  principle investigator

  PRINCIPAL INVESTIGATOR

• Jim Wright, MD

  OCOG Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Neoadjuvant Atezolizumab/Bevacizumab versus neoadjuvant SBRT in patients with biopsy proven solitary HCC with PVTT involving the portal vein branches.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 30, 2021
• Study Start: October 18, 2022
• Primary Completion: February 26, 2025
• Study Completion: February 26, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)