Durvalumab in Patients With HER-2 Positive Metastatic Breast Cancer Receiving Trastuzumab

NCT02649686 | Completed Phase 1 DMC

• 1 other identifier: I229
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find the highest dose of durvalumab that can be tolerated without causing very severe side effects when receiving standard treatment and to see what effects the study drug has on this type of cancer. The researchers doing this study are also interested in looking for markers that will help predict which patients are most likely to be helped by durvalumab when receiving standard treatment and what effects durvalumab has on this type of cancer.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Confirm the recommended phase II dose of durvalumab given to patients with advanced/recurrent HER-2 positive metastatic breast cancer (MBC) who are receiving treatment with trastuzumab

  18 months

Secondary Outcomes (4)

• Number of participants with treatment related adverse events as assessed by CTCAE V 4.0

  18 month

• Measure response rate of durvalumab measured by RECIST 1.1/Immune Response Criteria) in patients receiving trastuzumab

  18 months

• Measure clinical benefit rate of durvalumab measured by RECIST 1.1/Immune Response Criteria) in patients receiving trastuzumab

  18 months

• Assess PD-L1 expression in paired biopsies pre and post treatment with durvalumab as a marker of response/benefit

  18 months

Study Arms (1)

Durvalumab plus Trastuzumab

EXPERIMENTAL

Durvalumab q3w until PD Trastuzumab q3w x 6

Drug: Durvalumab; Drug: Trastuzumab

Interventions

Durvalumab DRUG

Durvalumab plus Trastuzumab

Trastuzumab DRUG

Durvalumab plus Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically and/or cytologically confirmed HER-2 positive (assessed locally and by current ASCO/CAP criteria) breast cancer that is advanced/metastatic/recurrent or unresectable and for which no curative therapy exists.
• Patients enrolled to the RP2D / expansion cohort must have accessible disease suitable for biopsy and have consented to biopsy prior to treatment and at the end of cycle 1. Paired biopsies are strongly recommended in all patients.
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
• All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows:
• Chest x-ray ≥ 20 mm
• CT scan (with slice thickness of 5 mm) ≥ 10 mm to longest diameter
• Physical exam (using calipers) ≥ 10 mm
• Lymph nodes by CT scan ≥ 15 mm to measured in short axis
• Patients must be ≥ 18 years of age.
• Patients must have an ECOG performance status of 0, 1, or 2.
• Previous Therapy
• Must have had prior exposure to a taxane, trastuzumab and pertuzumab\* and preferably also prior exposure to TDM-1.
• Taxane and pertuzumab may have been in the adjuvant or neoadjuvant setting.
• Must not be eligible for further trastuzumab treatment per provincial / formulary guidelines (i.e. patient has had two prior lines of either trastuzumab or lapatinib).
• Must have received at least one HER-2 based therapy in the palliative setting. \* Note: exceptions to the requirement for prior pertuzumab may be given. Consult CCTG.

You may not qualify if:

• Patients with a history of other malignancies requiring concurrent anticancer therapy.
• Patients with brain metastases are eligible providing that they have been treated, are stable (CT scan prior to enrolment mandatory for patients with known brain metastases) and patients are on a stable or decreasing dose of steroids (no more than equivalent of prednisone 10mg).
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 2 years prior to the start of treatment. The following are exceptions to this criterion: patients with vitiligo or alopecia, Graves' disease, hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 2 years).
• History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of registration or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy (NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible.)
• Live attenuated vaccination administered within 30 days prior to registration or within 30 days of receiving durvalumab.
• Any previous treatment with a PD-1 or PD-L1 inhibitor, or other immune based therapy including durvalumab.
• History of hypersensitivity to durvalumab or trastuzumab or any excipient.
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 ECGs using Fredericia's Correction.
• Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients should have a LVEF ≥ 50%.
• Concurrent treatment with other investigational drugs or anti-cancer therapy.
• Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study compliance.
• Active infection (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy).
• active peptic ulcer disease or gastritis
• Pregnant or lactating women. Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration. If test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (3)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Chia S, Bedard PL, Hilton J, Amir E, Gelmon K, Goodwin R, Villa D, Cabanero M, Tu D, Tsao M, Seymour L. A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2-Positive Metastatic Breast Cancer (CCTG IND.229). Oncologist. 2019 Nov;24(11):1439-1445. doi: 10.1634/theoncologist.2019-0321. Epub 2019 Aug 16.

  PMID: 31420468 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

durvalumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Stephen Chia

  BCCA-Vancouver Cancer Centre, Vancouver BC, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 7, 2016
• Study Start: May 17, 2016
• Primary Completion: September 25, 2017
• Study Completion: November 12, 2019
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)