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

NCT ID: NCT06502080

Last Updated: 2024-07-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2028-06-30

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.

Detailed Description

Standard-of-care systemic therapy with or without consolidative radiotherapy in patients with oligometastatic/locally advanced unresectable biliary tract cancer: an open-label, randomised, controlled study.

Eligible patients will be randomized in a 1:1 ratio to receive either current standard systemic therapy alone (control arm) or standard systemic therapy plus consolidative radiotherapy to all sites of known disease (experimental arm). Patients in both arms have the option of receiving upfront or subsequent standard palliative radiotherapy to any symptomatic sites requiring prompt intervention.

Because of the different treatment modalities in the study, it is not possible to blind the patient or physician to the treatment arm. Follow-ups for tumor assessment will conclude 2 years after randomization.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental group: consolidative radiotherapy group

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

Group Type: EXPERIMENTAL

Consolidative radiotherapy

Intervention Type: 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.

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

Intervention Type: DRUG

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

control group: standard-of-care systemic therapy alone

patients treated with standard-of-care systemic therapy

Group Type: OTHER

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

Intervention Type: DRUG

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

Interventions

Consolidative radiotherapy

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.

Intervention Type: RADIATION

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

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. 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.

6. Primary tumor lesions and all metastases of current diagnosis have not received local treatment, such as radiotherapy, surgery or radiofrequency ablation, prior to enrollment.

7. The patient is over 18 years old and has an Eastern Cooperative Oncology Group score of 0-1;

8. Life expectancy is greater than 12 weeks.

9. 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.

10. 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.

11. Each patient is voluntarily enrolled, and the informed consent form is signed by the patient or their legal representative.

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhaochong Zeng

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Zhongshan Hospital

Shanghai, , China

Countries

China

Central Contacts

Qianqian Zhao

Role: CONTACT

zhao.qianqian1@zs-hospital.sh.cn

+8618217008910

Zhaochong Zeng

Role: CONTACT

zeng.zhaochong@zs-hospital.sh.cn

+8613817076800

Facility Contacts

Zhaochong Zeng

Role: primary

zeng.zhaochong@zs-hospital.sh.cn

+8613817076800

Other Identifiers

ZSLCYJ202308

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

KY2024139

Identifier Type: -

Identifier Source: org_study_id