Trastuzumab plus chemotherapy versus chemotherapy alone for first-line HER2-positive advanced biliary tract cancer

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).

This trial will test if adding trastuzumab to standard first-line chemotherapy helps people with HER2-positive advanced or metastatic biliary tract cancer control their disease longer than chemotherapy alone.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Tata Memorial Centre (other)
• Drugs / interventions: trastuzumab, chemotherapy, radiation, Immunotherapy
• Locations: 6 sites (Muzaffarpur, Bihar and 5 other locations)
• Trial ID: NCT07062263 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase III trial that enrolls adults with unresectable or metastatic HER2-positive biliary tract adenocarcinoma and randomizes them 1:1 to receive gemcitabine/cisplatin (with or without nab-paclitaxel) either with or without trastuzumab. HER2 positivity is defined as IHC 3+ or IHC 2+ with FISH amplification. Treatment continues until disease progression or unacceptable toxicity, with regular clinical and imaging assessments to measure response and safety. The trial is being conducted at multiple tertiary cancer centers in India.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed unresectable or metastatic biliary tract adenocarcinoma that is HER2-positive (IHC 3+ or IHC 2+ with FISH amplification), fit for gemcitabine-based first-line chemotherapy, with ECOG 0–2 and adequate organ and cardiac function are ideal candidates.

Not a fit: Patients with HER2-negative tumors, resectable disease, significant cardiac dysfunction, or contraindications to trastuzumab or platinum/gemcitabine chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding trastuzumab could improve disease control and delay progression, and potentially extend survival for the HER2-positive subset of biliary tract cancer patients.

How similar studies have performed: Early-phase studies and a single-arm Phase II trial (TAB) have shown promising activity for trastuzumab combined with chemotherapy in HER2-positive biliary tract cancer, but definitive phase III evidence has been lacking until now.

Eligibility criteria

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the biliary tract, with the following specifications -

1. Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and perihilar cholangiocarcinoma.
2. HER2-positive by IHC or FISH
3. Age \>=18 years.
4. ECOG performance status 0 - 2.
5. Unresectable or metastatic cancer.
6. Patient does not have any contraindications to receive chemotherapy or trastuzumab.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. Negative serum pregnancy test (if applicable) and willing for adequate contraception.
13. At least one measurable disease according to RECIST criteria.
14. Life expectancy of at least 12 weeks.

Exclusion Criteria:

1. Distal cholangiocarcinoma
2. Known hypersensitivity or contraindications against gemcitabine, cisplatin, Nab- paclitaxel, or trastuzumab.
3. Clinically significant active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV.
4. Clinically significant valvular defect.
5. 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.
6. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
7. Baseline neuropathy \> NCI Grade I.
8. Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment.
9. Received prior chemotherapy within 1 year.
10. Any active ILD/ history of lung illness requiring bronchodilator drugs.
11. Patients with prior chemotherapy for metastatic disease will be ineligible for enrollment in the study.

Where this trial is running

Muzaffarpur, Bihar and 5 other locations

• Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur — Muzaffarpur, Bihar, India (NOT_YET_RECRUITING)
• Tata Memorial Hospital — Mumbai, Maharashtra, India (RECRUITING)
• Institute of Medical Sciences & SUM Hospital — Bhubaneswar, Odisha, India (NOT_YET_RECRUITING)
• Homi Bhabha Cancer Hospital and Research Centre — Mūllānpur, Punjab, India (RECRUITING)
• Mahamana Pandit Madan Mohan Malviya Cancer Centre (MPMMC) and Homi Bhabha Cancer Hospital (HBCH) — Varanasi, Uttar Pradesh, India (RECRUITING)
• MAX Super Speciality Hospital, SAKET — Delhi, India (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Vikas Ostwal, DM — Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India 400012
• Study coordinator: Vikas S Ostwal, DM

Conditions: Biliary Tract Cancer, HER2-positive Cancer, Advanced Cancer, Unresectable Biliary Tract Carcinoma, Metastatic Biliary Tract Carcinoma