Prospective collection of data of patients with liver cancers being treated with proton therapy

Recruiting

• Conditions: Malignant neoplasm of liver, primary, unspecified as to type,

• Registration Number: CTRI/2020/12/030087
• Lead Sponsor: Apollo Proton Cancer Centre

Brief Summary

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|**B****ackground and Rationale**

Hepatocellular carcinomas (HCC) have traditionally been cancers with dismal prognoses and limited options for treatment. Only a small proportion of patients are eligible for receiving curative treatments such as resection or liver transplant while the majority of patients are deemed ineligible for curative treatments due to advanced stage of disease or poor liver function.  Patients with such advanced tumours are then treated with a number of other modalities including minimally invasive locally ablative therapies such as radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial bland embolization, trans-arterial chemo-embolization (TACE) or trans-arterial radioembolization (TARE) and non-invasive ablative therapies such as stereotactic radiotherapy or proton beam therapy. Similarly, the use of radiation therapy, both SBRT and proton therapy, has been described in the case of unresectable intrahepatic cholangiocarcinoma (ICC). Proton beam therapy (PBT) for the treatment of HCC and ICC has been reported from several institutions in Japan, Korea and USA.  These studies showed encouraging outcomes in terms of response to therapy and side effect profile, even for large tumours, tumours with portal vein involvement and in patients with poor liver function at baseline. On the basis of the early Phase I and Phase II studies, currently a randomized controlled trial is ongoing in the USA comparing protons and photon-based radiotherapy in unresectable hepatocellular carcinomas. As the only proton centre in South Asia and the Middle East, Apollo Proton Cancer Centre (APCC) is in a unique situation to prospectively follow up all patients with liver tumours undergoing proton beam therapy at this centre to monitor their outcomes.

|**G****eneral aim**

To determine clinical outcomes (toxicity, local control, overall survival, and patterns of recurrence) in patients with, non-metastatic primary liver tumours treated with pencil-beam scanning proton beam therapy.

|**P****rimary objective(endpoint)**

 To report the proportion of patients developing decline in liver function at 1 and 3 months after proton therapy and the patient, tumour and treatment factors influencing this.

|**S****econdary objectives(endpoints)**

- Time to progression of the treated lesion and factors affecting these.

-Local control rates of lesions undergoing proton therapy and the patient, tumour and treatment characteristics influencing this.

-Overall survival and progression-free survival of all patients.

-Acute and late toxicity according to CTCAE v5.0.

-Quality of life for all patients using EORTC-QLQ-C30 and EORTC-QLQ-HCC18  or  EORTC-QLQ-BIL21at completion of treatment and at 1, 3, 6 & 12 months after treatment completion.

|**D****esign**

Observational Prospective

|**P****opulation**

All patients with primary liver tumors (hepatocellular cancer or intrahepatic cholangiocarcinomas) treated with proton therapy at the Apollo Proton Cancer Centre who consent to the study.

|**S****t****atistical considerations**

 Descriptive statistical analysis will be applied to routine demographic data collected, expressed as frequency for categorical variables. Chi-square test and Fisher’s exact test will be used for comparisons. Kaplan Meier curves will be used to summarize the time to event endpoints over time. Log-rank test will be used to test for differences in dichotomous variables in the time-to-event analysis. Factors significant in the univariate analysis will be tested by multivariate analysis using the Cox proportional hazard model.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-30
• Last Update Posted: 2021-08-16

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Adult patients 18years or older with histological or radiologic diagnosis of hepatocellular carcinoma, intrahepatic cholangiocarcinoma or mixed histology 2.
• Patients either deemed unresectable and/or locally recurrent OR who require bridging/down staging to orthotopic liver transplant OR who have tumour recurrence in a transplanted liver OR patients with any macrovascular invasion (tumour thrombosis of main portal vein, branch portal vein, segmental portal vein or hepatic vein, inferior vena cava).
• Patients must have normal organ and marrow function as defined below: a.
• Absolute neutrophil count ≥750 cells/μL b.
• Platelets ≥ 50,000 / μL c.
• Total bilirubin ≤ 4 times the institutional upper limit of normal d.
• Serum creatinine ≤ 2 mg/dl.
• Patients who have the ability to understand and be willing to sign a written informed consent document.

Exclusion Criteria

• Patients with extra hepatic disease (M1) except oligometastatic disease and intravascular tumour thrombosis.
• Patients with more than 7 tumours, except closely conglomerated lesions/satellite lesions.
• Performance status of ECOG 3 or more.
• Patients with Child Pugh score 10 or more, i.e. Child- Pugh Class C, except if patient is on anti-coagulant like warfarin.

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To report the proportion of patients developing decline in liver function at 1 and 3 months after proton beam therapy and the patient, tumour and treatment factors influencing this.	To report the proportion of patients developing decline in liver function at 1 and 3 months after proton beam therapy and the patient, tumour and treatment factors influencing this.

Secondary Outcome Measures

Name	Time	Method
To document the trends in quality of life of all patients using site-specific questionnaires: oEORTC-QLQ-C30 , oEORTC-QLQ-HCC18 , oEORTC-QLQ-BIL21	pre-treatment, post-treatment, 3 monthly, 6 monthly, 1 year, 2 year after treatment
To estimate the time to progression of irradiated hepatic lesion according to mRECIST criteria	1 year
To assess the overall survival and progression free survival as well as rates of patients at 2 years after proton therapy	2 years after proton therapy
To report the proportion of patients with ≥ Grade 2 toxicity to stomach, duodenum, small and large bowel, chest wall, skin, fatigue, nausea as well as biochemical parameters of liver function anytime within the first year after proton beam therapy, as per CTCAE (Version 5.0)criteria.	weekly during treatment, 3 monthly, 6 monthly, 1 year, 2 year after treatment
To estimate the rate of local control of irradiated lesions at 2 years post therapy, according to mRECIST criteria and RECIST 1.1 criteria.	2 years post therapy

Trial Locations

Locations (1)

Apollo Proton Cancer Centre; 🇮🇳 Chennai, TAMIL NADU, India

Apollo Proton Cancer Centre

🇮🇳Chennai, TAMIL NADU, India

Ashwathy Susan Mathew

Principal investigator

9769593681

drashwathy_m@apollohospitals.com