Consolidative Radiotherapy (CSRT) in Patients With Oligometastatic/Locally Advanced Unresectable Bilary Tract Cancer (BTC)

NCT06502080 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: KY2024139ZSLCYJ202308
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to investigate whether the inclusion of radiotherapy, in addition to standard-of-care systemic therapy, could improve the treatment effectiveness of patients with oligometastatic/locally advanced unresectable biliary tract cancer. The primary question that the trial aims to address is: does the addition of consolidative radiotherapy to standard-of-care systemic therapy for treating oligometastatic/locally advanced unresectable biliary tract cancer, result in a prolonged progression-free survival (PFS)? Researchers will assess whether radiotherapy can enhance PFS by comparing the survival time of patients with oligometastatic/locally advanced unresectable biliary tract cancer who receive standard-of-care systemic therapy alone versus those who receive standard-of-care systemic therapy along with consolidative radiotherapy. Participants in this trial will: Either receive or not receive consolidative radiotherapy following six cycles of standard-of-care systemic therapy.

Conditions

Biliary Tract Cancer

Keywords

biliary tract cancer; consolidative radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression free survival is defined as the duration between the date of randomization to the date of first documented progression or death due to any cause or date of last follow-up, whichever is earlier.

  Upto 2 years

Secondary Outcomes (7)

• Overall survival (OS)

  Upto 2 years

• Local control rates of treated sites

  Upto 2 years

• New distant metastases

  Upto 2 years

• Response rates

  From randomization every 3 months upto 2 years

• Health Related QOL using the EORTC-QLQ-C30 questionnaire

  From randomization every 3 months till 2 years

Study Arms (2)

Experimental group: consolidative radiotherapy group

EXPERIMENTAL

patients treated with standard-of-care systemic therapy combined with consolidative radiotherapy

Radiation: Consolidative radiotherapy; Drug: Standard-of-care systemic therapy: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab

control group: standard-of-care systemic therapy alone

OTHER

patients treated with standard-of-care systemic therapy

Drug: Standard-of-care systemic therapy: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab

Interventions

Consolidative radiotherapy RADIATION

Consolidative radiotherapy: total dose and number of fractions will depend on the site of disease. Treatment will be given daily, or every other day, over 1 -3 weeks. Physicians should try to give the highest BED whenever possible while respecting normal tissue tolerance. All lesions are recommended to receive a biologically effective dose (BED) of 60 Gy or higher (BED10≥70), assuming α/β ratio of 10 and using the linear-quadratic model: BED = nd x \[1 + d/(α/β)\] where n is number of fractions and d is dose per fraction. Sometimes BED ≥80 Gy is preferred, with lower doses ≥50 Gy allowed at the discretion of the treating physician for concerns about normal tissue toxicity.

Experimental group: consolidative radiotherapy group

Standard-of-care systemic therapy: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab DRUG

Standard-of-care systemic therapy as decided by the treating medical oncologist: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab

Experimental group: consolidative radiotherapy group; control group: standard-of-care systemic therapy alone

Eligibility Criteria

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

You may qualify if:

• The disease has not progressed following the restaging imaging evaluation in patients with oligometastatic/locally advanced unresectable BTC after four cycles of first-line systemic treatment.
• 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.
• 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.
• 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.
• Primary tumor lesions and all metastases of current diagnosis have not received local treatment, such as radiotherapy, surgery or radiofrequency ablation, prior to enrollment.
• The patient is over 18 years old and has an Eastern Cooperative Oncology Group score of 0-1;
• Life expectancy is greater than 12 weeks.
• 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.
• 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.
• Each patient is voluntarily enrolled, and the informed consent form is signed by the patient or their legal representative.

You may not qualify if:

• Histology includes components of mixed hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or biliary adenocarcinoma.
• Complete response to four cycles of first-line systemic treatment (i.e. no measurable target for radiotherapy).
• There is new metastasis during the four cycles of first-line systemic treatment and the number of metastases is more than five.
• Patient has uncontrolled brain metastases or vertebral body metastasis with spinal cord compression symptoms.
• Patient has uncontrolled pleural, pericardial or pelvic effusion that requires repeated drainage.
• Patient is a pregnant or breastfeeding woman.
• Patient has a history of immunodeficiency or severe medical disease that is not well controlled and may have an effect on study treatment.
• 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.
• 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

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Cisplatin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Zhaochong Zeng

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qianqian Zhao

CONTACT

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

Zhaochong Zeng

CONTACT

+8613817076800; zeng.zhaochong@zs-hospital.sh.cn

Study Design

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

Study Record Dates

• First Submitted: July 7, 2024
• First Posted: July 15, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)