Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Postive Advanced Gastroesophageal Adenocarcinoma

A Randomized Phase II Study of Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Positive Advanced Gastroesophageal Adenocarcinoma

This study is being done to answer the following question:

Can the chance of gastroesophageal cancer growing or spreading be lowered by adding a drug called zanidatamab to the usual combination of drugs?

We are doing this study because we want to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as care most people get for gastroesophageal cancer

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Adenocarcinoma
• Intervention / Treatment: Drug: Paclitaxel; Drug: Ramucirumab; Drug: Zanidatamab

Detailed Description

The purpose of this study is to compare the usual approach alone to using zanidatamab plus the usual approach. The addition of zanidatamab to the usual approach could shrink cancer. But, it could also cause side effects.

This study will help the study doctors find out if this different approach is better than the usual approach. To decide if it is better, the study doctors will be looking to see if adding zanidatamab to the usual approach reduces the risk of cancer getting worse by at least 37% compared to the usual approach.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chris O'Callaghan; Phone Number: 613-533-6430; Email: cocallaghan@ctg.queensu.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Arthur J.E. Child Comprehensive Cancer Centre
      • Contact: Hatim Karachiwala
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BCCA - Vancouver
      • Contact: Howard Lim; Phone Number: 672699 604 877-6000
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Recruiting
      • CancerCare Manitoba
      • Contact: James T. Paul; Phone Number: 204 787-2108
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Recruiting
      • QEII Health Sciences Centre
      • Contact: Stephanie Snow; Phone Number: 902 473-3739
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Recruiting
      • Royal Victoria Regional Health Centre
      • Contact: Dawn Ng; Phone Number: 43340 705 728-9090
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre at Hamilton Health Sciences
      • Contact: Oren Levine; Phone Number: 63123 905 387-9495
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: Brooke Wilson
    • Kitchener, Ontario, Canada, N2G 1G3
      • Recruiting
      • Waterloo Regional Health Network (WRHN)
      • Contact: Anupam Batra
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre Research Inc.
      • Contact: Daniel Breadner; Phone Number: 519 685-8600
    • Oshawa, Ontario, Canada, L1G 2B9
      • Recruiting
      • Lakeridge Health Oshawa
      • Contact: Amin Kay
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Rachel Goodwin; Phone Number: 70185 613 737-8899
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's Hospital
      • Contact: Suneil Khanna; Phone Number: 416 864-5734
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network
      • Contact: Elena Elimova; Phone Number: 2520 416 946-4501
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Odette Cancer Centre
      • Contact: Michael Raphael; Phone Number: 416 480-5000
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • CHUM-Centre Hospitalier de l'Universite de Montreal
      • Contact: Moustapha Tehfe; Phone Number: 25381 514 890-8000
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Centre Integre Universitaire De Sante Et De Services
      • Contact: Setareh Samimi; Phone Number: 514 338-2150
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Recruiting
      • Allan Blair Cancer Centre
      • Contact: Muhammad Salim; Phone Number: 306 766-2691
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Recruiting
      • Saskatoon Cancer Centre
      • Contact: Adnan Zaidi; Phone Number: 306 655-2710

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically or pathologically confirmed gastroesophageal adenocarcinoma (stomach, gastroesophageal junction or esophagus) that is unresectable or metastatic and which must be HER2 positive as confirmed by central testing using FDA-approved HER2 assay. HER2 positive is defined as IHC 3+, or IHC 2+ and FISH positive.
• Participants must have received and failed at least one prior trastuzumab-containing regimen in combination with platinum-based chemotherapy for treatment of locally advanced or metastatic disease. Failure is defined as demonstrated objective disease progression (radiologic) on the most recently administered HER2 targeting agent.
• Participants must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
• Participants must be considered a suitable candidate for, and able to receive chemotherapy for advanced disease with paclitaxel and ramucirumab.
• Participants must consent to the provision of samples of blood, serum and plasma in order that the specific correlative marker assays may be conducted.
• Participants must consent to provision of, and investigator(s) must confirm access to a representative formalin fixed paraffin embedded (FFPE) block of tumour tissue/ or a predetermined number of freshly cut slides of representative tumour tissue of adequate amount and quality in order that the central HER2 testing may be done
• Participants must be ≥ 18 years of age.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants must have a life expectancy of at least 12 weeks at the time of study entry
• Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be done within 28 days prior to randomization
• Participants must have adequate cardiac function by ECHO or MUGA defined as EF ≥ 50%. This is to be performed within 4 weeks (preferred) but no more than 8 weeks prior to randomization
• Participants must have adequate normal organ and marrow function
• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English or French
• Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Participant must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrollment
• Participants of childbearing potential must have agreed to use a highly effective contraceptive method for the entire period of study treatment and for at least 7 months after discontinuing study therapy.

Exclusion Criteria:

• Participants with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at a low risk of recurrence MAY be eligible
• Participants receiving therapy in a concurrent clinical study. Patients must agree not to participate in other clinical studies during their participation in this trial while on study treatment
• Participants with active or uncontrolled intercurrent illness
• Participants with human immunodeficiency virus infection (positive HIV 1/2 antibodies), active hepatitis B infection (positive HBV surface antigen (HBsAg)) or positive for hepatitis C (HCV) antibody may be considered for enrollment, if infection is adequately controlled in the opinion of the investigator.
• Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
• Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
• Any unresolved toxicity (CTCAE grade 2 or greater) from previous anti-cancer therapy which in the opinion of the investigator puts the participant at higher than expected risk during protocol treatment. However, participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational products in the Investigator's opinion may be included.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paclitaxel and Ramucriumab	Drug: Paclitaxel; 80 mg/m²; Drug: Ramucirumab; 8 mg/kg
Experimental: Zanidatamab + Paclitaxel and Ramucirumab	Drug: Paclitaxel; 80 mg/m²; Drug: Ramucirumab; 8 mg/kg; Drug: Zanidatamab; Dose and schedule to be assigned at enrollment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	36 months
Objective response rate	36 months
Number and severity of adverse events	36 months
Quality of Life utilizing the EORTC QLQ C30	36 months
Quality of Life utilizing the EORTC QLQ-OES18	36 months

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Jazz Pharmaceuticals
• Investigators: Study Chair: Elena Elimova, University Health Network, Princess Margaret Cancer Centre, Toronto ON Canada

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Ramucirumab; Paclitaxel; zanidatamab
• Other Study ID Numbers: GA4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No