Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients

NCT07062263 | Recruiting Phase 3 DMC

• 1 other identifier: 4172
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Biliary Tract Cancer; HER2-positive Cancer; Advanced Cancer; Unresectable Biliary Tract Carcinoma; Metastatic Biliary Tract Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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

  at 6 month after randomisation

Secondary Outcomes (4)

• 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)

Study Arms (2)

Arm A: Trastuzumab plus Chemotherapy

EXPERIMENTAL

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

Drug: Trastuzumab; Drug: Chemotherapy

Arm B: Chemotherapy alone

ACTIVE COMPARATOR

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

Drug: Chemotherapy

Interventions

Trastuzumab DRUG

Inj Trastuzumab given in a dose of 8mg/kg intravenously over 90 mins as first dose and subsequent doses at a dose of 6mg/kg intravenously over 30-60 minutes in 3 weekly cycle along with standard of care chemotherapy

Also known as: Transtuzumab with standand of chemotherapy

Arm A: Trastuzumab plus Chemotherapy

Chemotherapy DRUG

Gemcitabine + cisplatin OR Gemcitabine-cisplatin-Nab-Paclitaxel given as a standard of care, chemotherapy as per the institutional guidlines

Also known as: Standard of chemotherapy, Gemcitabine, cisplatin, Nab-Paclitaxel

Arm A: Trastuzumab plus Chemotherapy; Arm B: Chemotherapy alone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 - 2.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (6)

Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur

Muzaffarpur, Bihar, 842004, India

NOT YET RECRUITING

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

RECRUITING

Institute of Medical Sciences & SUM Hospital

Bhubaneswar, Odisha, 751003, India

NOT YET RECRUITING

Homi Bhabha Cancer Hospital and Research Centre

Mūllānpur, Punjab, 140901, India

RECRUITING

Mahamana Pandit Madan Mohan Malviya Cancer Centre (MPMMC) and Homi Bhabha Cancer Hospital (HBCH)

Varanasi, Uttar Pradesh, 221005, India

RECRUITING

MAX Super Speciality Hospital, SAKET

Delhi, 110017, India

NOT YET RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Trastuzumab; Drug Therapy; Gemcitabine; Cisplatin; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Vikas Ostwal, DM

  Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India 400012

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vikas S Ostwal, DM

CONTACT

0222417000; dr.vikas.ostwal@gmail.com

Anant Ramaswamy, DM

CONTACT

0222417000; anantr13@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dept of Medical Oncology, Convener Gastro-Intestinal Disease Management Group

Model Details: Phase III open-label parallel design randomized clinical trial

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 14, 2025
• Study Start: July 21, 2023
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (6)