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

NCT06043427 | Recruiting Phase 2 DMC

• 1 other identifier: GA4
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 18

Brief Summary

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

Conditions

Gastroesophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  36 months

Secondary Outcomes (5)

• 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

Study Arms (2)

Paclitaxel and Ramucriumab

ACTIVE COMPARATOR

Drug: Paclitaxel; Drug: Ramucirumab

Zanidatamab + Paclitaxel and Ramucirumab

EXPERIMENTAL

Drug: Paclitaxel; Drug: Ramucirumab; Drug: Zanidatamab

Interventions

Ramucirumab DRUG

8 mg/kg

Paclitaxel and Ramucriumab; Zanidatamab + Paclitaxel and Ramucirumab

Zanidatamab DRUG

Dose and schedule to be assigned at enrollment

Zanidatamab + Paclitaxel and Ramucirumab

Paclitaxel DRUG

80 mg/m²

Paclitaxel and Ramucriumab; Zanidatamab + Paclitaxel and Ramucirumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: collaborator
• Canadian Cancer Trials Group: lead

Study Sites (18)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

RECRUITING

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Waterloo Regional Health Network (WRHN)

Kitchener, Ontario, N2G 1G3, Canada

RECRUITING

London Health Sciences Centre Research Inc.

London, Ontario, N6A 5W9, Canada

RECRUITING

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Centre Integre Universitaire De Sante Et De Services

Montreal, Quebec, H4J 1C5, Canada

RECRUITING

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

RECRUITING

MeSH Terms

Interventions

Paclitaxel; Ramucirumab; zanidatamab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Elena Elimova

  University Health Network, Princess Margaret Cancer Centre, Toronto ON Canada

  STUDY CHAIR

Central Study Contacts

Chris O'Callaghan

CONTACT

613-533-6430; cocallaghan@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 21, 2023
• Study Start: April 16, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (18)