FOLFOX Combined With Durvalumab (MEDI4736), Bevacizumab, and Stereotactic Body Radiotherapy in Sequential Treatment of Potentially Resectable Locally Advanced Hepatocellular Carcinoma

NCT07012798 | Not Yet Recruiting Phase 2

• 1 other identifier: DB-HERO
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Study Design: This is a pilot study with a single arm in a single centre assessing safety and efficacy of durvalumab in combination with bevacizumab and HAIC followed by SBRT. This study will be conducted in selected patients with intermediate or advanced stage HCC not amenable to curative therapy. Approximately 30 patients will be enrolled and receive treatments. Primary Objectives: To evaluate the possibility of HAIC plus durvalumab and bevacizumab followed by SBRT as conversion therapy for HCC. Secondary Objective(s): To evaluate the efficacy of HAIC plus durvalumab and bevacizumab followed by SBRT for HCC. To evaluate the safety of HAIC plus durvalumab and bevacizumab followed by SBRT for HCC. Exploratory Objective(s): Evaluate the consistency of imaging CR and pathological CR in resected patients, and explore biomarkers associated with prognosis .

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Durvalumab; HAIC; SBRT; Conversion Therapy

Outcome Measures

Primary Outcomes (1)

• Conversion rate

  3 MONTH

Secondary Outcomes (4)

• Overall response rate (ORR) measured by RECIST v1.1, mRECIST.

  6 MONTH

• Pathological complete response (pCR) for patients received resection.

  6 MONTH

• Major pathologic response (MPR) for patients received resection.

  6 MONTH

• AE

  6 MONTH

Study Arms (1)

TREATMENT

EXPERIMENTAL

therapy of durvalumab in combination with bevacizumab, combined with HAIC followed by SBRT

Drug: Durvalumab; Drug: Bevacizumab; Drug: HAIC of FOLFOX

Interventions

Durvalumab DRUG

1120mg, iv, q3w

TREATMENT

Bevacizumab DRUG

15mg/kg, iv, q3w

TREATMENT

HAIC of FOLFOX DRUG

HAIC (FOLFOX): oxaliplatin 100mg/m2, 4h, day 1 + leucovorin 300mg/m2, 2h, day 1 + fluorouracil 500mg/m2, 20min, day 1 + fluorouracil 1500mg/m2, 20h, q3w

TREATMENT

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years.
• Have a HCC diagnosis confirmed by radiology, histology, or cytology.
• HCC newly diagnosed or recurrent with a history of surgery or ablation, not amenable to curative surgery or transplantation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to screening.
• Tumours were classified as unresectable after a multidisciplinary team review because either:
• R0 resection was not feasible
• Sum of tumor diameters ≥5cm
• A maximum of three tumour lesions
• For patients with tumors located in bilateral hepatic lobes, the study requires that the number of tumors in the contralateral hepatic lobe of the larger tumor be less than 3, and the maximum tumor diameter should not exceed 3 cm.
• Child-Pugh liver function score A.
• Intrahepatic vascular invasion includes intrahepatic portal vein branch invasion, left or right portal vein invasion was allowed.
• Patients with oligometastasis, defined as having a single metastatic organ with three or fewer metastases, each less than 3cm in size were permitted.
• No prior radiotherapy or radioembolization to the liver or upper abdomen was allowed. Prior local therapies, such as surgery, radiofrequency ablation, percutaneous ethanol injection or cryoablation, are allowed if the index lesion(s) remain outside of the treatment field or have progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan.

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or infiltrative-type HCC.
• Intrahepatic or Extrahepatic vascular involvement: main hepatic vein invasion (VP3) or main portal vein (VP4).
• Prior radiotherapy to the liver or upper abdomen.
• Participation in another clinical study with an investigational product.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the systematic anticancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, monoclonal antibodies) prior to the first dose of study drug.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Cancer Hospital Airport Hospital

Tianjin, Tianjin Municipality, 300308, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; Bevacizumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Huikai Li

CONTACT

18622228633; tjchlhk@126.com

Study Design

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

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 10, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-05

Locations

CN (1)