Biliary Tract Cancer
Conditions
Keywords
biliary tract cancer, consolidative radiotherapy
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.
Interventions
RADIATIONConsolidative 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.
DRUGStandard-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
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. 5. Patients who experience recurrence after curative surgery with a time interval of \>6 months can be eligible for inclusion. If adjuvant therapy (excluding radiotherapy) is administered, the patient must have completed adjuvant therapy for a period of at least 6 months before meeting the inclusion criteria. 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. 5. The toxicity of previous antitumor treatment has not recovered to ≤1 based on National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 (except for hair loss) or the level specified by the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Upto 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local control rates of treated sites | Upto 2 years | Local control rate will be defined as the absence of progressive disease at the treated sites. |
| New distant metastases | Upto 2 years | Time to onset of new distant metastases. |
| Response rates | From randomization every 3 months upto 2 years | To compare response rates between the two arms. |
| Overall survival (OS) | Upto 2 years | Overall survival is defined as the duration between the date of randomization to the date of death due to any cause or the date of last follow-up, whichever is earlier. |
| Health Related QOL using the EORTC QLQ-BIL21 questionnaire | From randomization every 3 months till 2 years | To evaluate patient reported outcomes between the two arms. EORTC QLQ-BIL21 (European Organisation for Research and Treatment of Cancer questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder), scores range from 0 to 100, where a lower score means a better quality of life. |
| Radiotherapy related toxicity using CTC v5.0 (radiotherapy related acute and late toxicity) | Upto 2 years | At baseline and at subsequent follow up till 2 years. |
| Health Related QOL using the EORTC-QLQ-C30 questionnaire | From randomization every 3 months till 2 years | To evaluate patient reported outcomes between the two arms. EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms. |
Countries
China
Contacts
Primary ContactQianqian Zhao
Backup ContactZhaochong Zeng
Outcome results
None listed