Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients - a Randomized Non-blinded Two-arm Phase III Prospective Clinical Trial (TAB-2 Study).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 6
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a randomized, open-label, two-arm, Phase III clinical trial evaluating the efficacy and safety of trastuzumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with HER2-positive advanced or metastatic biliary tract cancers (BTC). HER2-positive BTCs represent a molecular subset of these rare cancers, associated with poor prognosis and limited treatment options.
Eligible patients with histologically confirmed HER2-positive (IHC 3+ or IHC 2+ with FISH amplification) unresectable or metastatic biliary tract adenocarcinoma-including gallbladder cancer, intrahepatic, and perihilar cholangiocarcinoma-will be randomized in a 1:1 ratio. Participants in the intervention arm (Arm A) will receive either gemcitabine and cisplatin with or without nab-paclitaxel plus trastuzumab, while those in the control arm (Arm B) will receive chemotherapy alone (gemcitabine + cisplatin with or without nab-paclitaxel). Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or death.
The primary endpoint is 6-month progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate (RR), quality of life (QOL), and adverse event (AE) profiles. The study aims to enroll 196 patients across a single center in India over a period of 5 years, with an additional 6-month follow-up. This trial builds on earlier Phase II findings suggesting improved outcomes with trastuzumab in HER2-positive BTC and aims to provide the first randomized evidence for the benefit of HER2-targeted therapy in this setting.
详细描述
Title of study- Trastuzumab plus chemotherapy vs Chemotherapy alone in first-line HER2 positive advanced biliary tract cancer patients - a randomized non-blinded two-arm Phase III prospective clinical trial (TAB - 2 study)
Indication- HER2-positive advanced/metastatic biliary tract cancers fit for first-line chemotherapy with gemcitabine-based combination
Type of Study- Two arm open-label prospective Phase III parallel design randomized superiority clinical trial
Biliary tract cancers (BTC), including gallbladder cancer and cholangiocarcinomas, are uncommon but aggressive tumors with poor prognosis in the advanced or metastatic setting. The current standard first-line treatment is gemcitabine combined with a platinum agent, which offers limited benefit. Emerging molecular profiling has identified HER2 overexpression or amplification in a subset of BTCs, particularly in gallbladder cancer, and has opened new avenues for targeted therapy.
Trastuzumab, a monoclonal antibody targeting the HER2 receptor, has shown clinical activity in HER2-positive BTCs in early-phase studies. Preliminary evidence from a single-arm Phase II study (TAB trial) suggests that combining trastuzumab with chemotherapy may significantly improve progression-free survival in treatment-naïve HER2-positive patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the biliary tract, with the following specifications -
- •Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and perihilar cholangiocarcinoma.
- •HER2-positive by IHC or FISH
- •Age >=18 years.
- •ECOG performance status 0 -
- •Unresectable or metastatic cancer.
- •Patient does not have any contraindications to receive chemotherapy or trastuzumab.
- •Adequate hematological, hepatic, and renal function parameters- Hematological- Hb> 80 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L. Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT ≤ 5 x ULN, alkaline phosphatase ≤ 6 x upper limit normal (ULN) S. albumin ≥ 30 g/L.
- •Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance >= 30 mL/min.
- •Normal cardiac ejection fraction and cardiac function, as assessed by echocardiography, ejection fraction (EF) >=50% or above the lower limit of normal. ECG with no clinically relevant abnormalities.
- •Women of childbearing age should have a negative pregnancy test at the time of randomization and should be willing to use adequate contraception during the treatment phase of the trial.
- •Subjects must provide written informed consent prior to the performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up assessments and procedures.
- •Subjects who have received adjuvant chemotherapy will be considered eligible provided that therapy is completed more than 12 months before study enrollment. Patients who have received radiation therapy and surgery will also be eligible provided the interventions have been completed 3 and 2 weeks, respectively, before enrolment in the study.
- •Negative serum pregnancy test (if applicable) and willing for adequate contraception.
- •At least one measurable disease according to RECIST criteria.
- •Life expectancy of at least 12 weeks.
排除标准
- •Distal cholangiocarcinoma
- •Known hypersensitivity or contraindications against gemcitabine, cisplatin, Nab- paclitaxel, or trastuzumab.
- •Clinically significant active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV.
- •Clinically significant valvular defect.
- •Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix.
- •Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
- •Baseline neuropathy > NCI Grade I.
- •Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment.
- •Received prior chemotherapy within 1 year.
- •Any active ILD/ history of lung illness requiring bronchodilator drugs.
- •Patients with prior chemotherapy for metastatic disease will be ineligible for enrollment in the study.
研究组 & 干预措施
Arm A: Trastuzumab plus Chemotherapy
Trastuzumab + Gemcitabine + cisplatin
- Gemcitabine 1000 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly
- Trastuzumab 8mg/kg IV over 90 mins as first dose and subsequent doses at 6mg/kg IV over 30-60 minutes q 3 weekly (=1 cycle)
OR
- Trastuzumab with Gemcitabine-cisplatin-Nab-Paclitaxel
- Gemcitabine 800 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Nab-paclitaxel 100 mg/m2 IV over 1-2 hours on day 1 and day 8 q 3 weekly
- Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly
- Trastuzumab 8mg/kg IV over 90 mins as first dose and subsequent doses at 6mg/kg IV over 30-60 minutes q 3 weekly (=1 cycle) Start of next cycle on D22 Immunotherapy is allowed as per the discretion of the treating physician
干预措施: Trastuzumab (Drug)
Arm A: Trastuzumab plus Chemotherapy
Trastuzumab + Gemcitabine + cisplatin
- Gemcitabine 1000 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly
- Trastuzumab 8mg/kg IV over 90 mins as first dose and subsequent doses at 6mg/kg IV over 30-60 minutes q 3 weekly (=1 cycle)
OR
- Trastuzumab with Gemcitabine-cisplatin-Nab-Paclitaxel
- Gemcitabine 800 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Nab-paclitaxel 100 mg/m2 IV over 1-2 hours on day 1 and day 8 q 3 weekly
- Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly
- Trastuzumab 8mg/kg IV over 90 mins as first dose and subsequent doses at 6mg/kg IV over 30-60 minutes q 3 weekly (=1 cycle) Start of next cycle on D22 Immunotherapy is allowed as per the discretion of the treating physician
干预措施: Chemotherapy (Drug)
Arm B: Chemotherapy alone
Gemcitabine + cisplatin
- Gemcitabine 1000 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly (=1 cycle)
OR
- Gemcitabine-cisplatin-Nab-Paclitaxel
- Gemcitabine 800 mg/m2 IV over 30 mins on day 1 and day 8 q 3 weekly
- Nab-paclitaxel 100 mg/m2 IV over 1-2 hours on day 1 and day 8 q 3 weekly =Cisplatin 25 mg/m2 IV over 60 minutes on day 1 and day 8 q 3 weekly (=1 cycle) Start of next cycle on D22 Immunotherapy is allowed as per the discretion of the treating physician
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: at 6 month after randomisation
the time from the time of diagnosis of an advanced disease to the time of disease progression or loss to follow-up or death, whichever is earlier
次要结局
- Overall survival (OS)(at 6month, 1 year from the date of randomisation or till the time of death, lost to follow-up or last observation, whichever is earlier)
- Response rates(at 6th month from the date of randomisation)
- Quality of life (QOL)(at baseline and at completion of 4 cycles of chemotherapy (each cycle is 22 days))
- Safety profile("At the end of each Cycle (each cycle is 22 days))
研究者
Dr. Vikas Ostwal
Professor Dept of Medical Oncology, Convener Gastro-Intestinal Disease Management Group
Tata Memorial Centre