Second-line Regimen Combined With Radiotherapy Versus Without Radiotherapy in Patients With Locally Advanced/Oligometastatic ICC After Failure of First-line Treatment：an Open-label, Randomized, Controlled Phase II Clinical Study

NCT06946849 | Not Yet Recruiting Phase 2

• 2 other identifiers: KY2025087KY2025XXX
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Second-line regimen with or without consolidative radiotherapy in patients with oligometastatic/locally advanced unresectable intrahepatic cholangiocarcinoma: an open-label, randomised, controlled study.

Conditions

Intrahepatic Cholangiocarcinoma (Icc)

Keywords

Intrahepatic Cholangiocarcinoma, Radiotherapy, Second-line regimen

Outcome Measures

Primary Outcomes (1)

• PFS

  PFS is will be measured from the randomization to progression or death from any cause. Progression includes enlargement of target lesions and development of new distant metastases and will be assessed using RECIST 1.1.

  Up to 2 years

Secondary Outcomes (3)

• OS

  Up to 2 years

• LCR

  Up to 2 years

• AEs

  Up to 2 years

Study Arms (2)

2L SoC+RT

EXPERIMENTAL

2L SoC regimen combined with radiotherapy

Radiation: radiotherapy; Drug: FOLFIRI or FOLFOX or Regorafenib

2L-SoC

ACTIVE COMPARATOR

Drug: FOLFIRI or FOLFOX or Regorafenib

Interventions

radiotherapy RADIATION

Radiotherapy

2L SoC+RT

FOLFIRI or FOLFOX or Regorafenib DRUG

FOLFIRI or FOLFOX or Regorafenib

2L SoC+RT; 2L-SoC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) Advanced or metastatic intrahepatic cholangiocarcinoma confirmed by histopathology that cannot be surgically removed.
• (2) Failed to receive first-line standard treatment. (3) Definition of oligometastatic/locally advanced unresectable BTC disease: not a candidate for surgical resection at all sites: surgery to all sites not recommended by multidisciplinary team, or unfit or declining surgery.
• (4) Definition of oligometastatic disease: patients with distant organ metastasis or nonregional lymph node metastasis, or distant organ/nonregional lymph node metastasis and regional lymph node metastasis, as defined by the American Joint Committee on Cancer, 8th edition. The total number of metastases is ≤5 and the number of metastases in any single organ system (e.g., lung, liver) is ≤3.
• (4) All sites of disease must be amenable to radiotherapy and can be safely treated. Each lesion is counted separately at the time of registration and contributes to the total number of metastases. For regional lymph nodes metastases, all positive regional lymph nodes are counted together as one lesion. For nonregional lymph node metastases, adjacent metastatic lymph nodes can be treated as one lesion. Lesions that have subsided during previous treatment (i.e., are no longer visible on CT scan or have eliminated affinity on positron emission tomography \[PET\]-CT) are not included in the total number. At least one metastatic lesion meets the RECIST v1.1 criteria for assessable lesions. Bone metastases without soft tissue involvement can be included but are not considered assessable lesions. However, if bone metastases have soft tissue involvement and meet the criteria for assessable lesions, they are considered measurable lesions.
• (5) Primary tumor lesions and all metastases of current diagnosis have not received local treatment, such as radiotherapy, surgery or radiofrequency ablation, prior to enrollment.
• (6) The patient is over 18 years old and has an Eastern Cooperative Oncology Group score of 0-1; (7) Life expectancy is greater than 12 weeks. (8) Vital organ function meets the following requirements: absolute neutrophil count ≥1.5 × 109/l; platelet count ≥100 × 109/l; hemoglobin ≥9 g/dl; serum albumin ≥2.8 g/dl; total bilirubin ≤1.5 × upper limit of normal (ULN) and alanine transaminase, aspartate aminotransferase and/or alkaline phosphatase ≤2.5 × ULN (if there is liver metastasis, alanine transaminase and/or aspartate aminotransferase ≤5 × ULN; if there is liver metastasis or bone metastasis, alkaline phosphatase ≤5 × ULN); serum creatinine ≤1.5 × ULN or creatinine clearance \>60 ml/min. For patients with pulmonary lesions or previous lung irradiation who are known or suspected to have impaired lung function, the forced expiratory volume for 1 second of lung function must be above 1 l.
• (9) Female subjects of childbearing age must have a negative urine or serum pregnancy test within 72 h prior to randomization. Subjects must agree to adequate contraception during the trial.
• (10) Each patient is voluntarily enrolled, and the informed consent form is signed by the patient or their legal representative.

You may not qualify if:

• (1) Histology includes components of mixed hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or biliary adenocarcinoma.
• (2) Complete response to four cycles of first-line systemic treatment (i.e. no measurable target for radiotherapy).
• (3) There is new metastasis during the four cycles of first-line systemic treatment and the number of metastases is more than five.
• (4) Patient has uncontrolled brain metastases or vertebral body metastasis with spinal cord compression symptoms.
• (6) Patient has uncontrolled pleural, pericardial or pelvic effusion that requires repeated drainage.
• (7) Patient is a pregnant or breastfeeding woman. (8) Patient has a history of immunodeficiency or severe medical disease that is not well controlled and may have an effect on study treatment.
• (9) Any other malignant tumor has been diagnosed within 5 years prior to or after the diagnosis of BTC, except for malignant tumors with a low risk of metastasis and death (5-year survival rate \>90%), such as well-treated basal cell or squamous cell skin cancer or cervical cancer in situ.
• (10) Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

Radiotherapy; Folfox protocol; regorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Zhaochong Zeng

  Zhongshan Hospital, Fudan Unuversity

  PRINCIPAL INVESTIGATOR

• Guoming Shi

  Zhongshan Hospital, Fudan Unuversity

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qianqian Zhao

CONTACT

+8618217008910; zhao.qianqian1@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: April 19, 2025
• First Posted: April 27, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)