A Prospective, Single-arm, Single-center Phase II Clinical Study of Hepatic Artery Infusion Chemotherapy (FOLFOX) Combined With Durvalumab (MEDI4736), Bevacizumab, and Stereotactic Body Radiotherapy in Sequential Treatment of Potentially Resectable Locally Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Conversion rate
Overview
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 .
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
Exclusion Criteria
- •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.
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •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.
Arms & Interventions
TREATMENT
therapy of durvalumab in combination with bevacizumab, combined with HAIC followed by SBRT
Intervention: Durvalumab (Drug)
TREATMENT
therapy of durvalumab in combination with bevacizumab, combined with HAIC followed by SBRT
Intervention: Bevacizumab (Drug)
TREATMENT
therapy of durvalumab in combination with bevacizumab, combined with HAIC followed by SBRT
Intervention: HAIC of FOLFOX (Drug)
Outcomes
Primary Outcomes
Conversion rate
Time Frame: 3 MONTH
Secondary Outcomes
- 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)