T-DM1 and Non-pegylated Liposomal Doxorubicin in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

NCT02562378 | Completed Phase 1 Results

• 2 other identifiers: MedOPP0382014-001056-28
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 4

Brief Summary

The primary goal is to determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy. In addition, pharmacokinetic data on the combination of T-DM1 and liposomal doxorubicin will be obtained.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Hematological - Dose Limiting Toxicities

  Treatment-related adverse events (AEs) of any grade reported in ≥10% of patients.

  Baseline up to 6 weeks after patient entry (Cycle2Day21)

• Non-Hematological - Dose Limiting Toxicities

  Treatment-related AEs of any grade reported in ≥10% of patients.

  Baseline up to 6 weeks after patient entry (Cycle2Day21)

Secondary Outcomes (18)

• Overall Response Rate

  Baseline up to 24 months after patient entry

• Best Overall Response

  Baseline up to 24 months after patient entry

• Clinical Benefit Rate

  Baseline up to 24 months after patient entry

• Progression-free Survival

  Baseline up to 24 months after patient entry

• Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations

  Baseline up to 24 months after patient entry

Study Arms (1)

Experimental arm

EXPERIMENTAL

Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and three cohorts of patients with three different dose levels of conventional non-pegylated liposomal doxorubicin (45 mg/m2, 50 mg/m2 and 60 mg/m2) IV

Drug: Trastuzumab and non-pegylated liposomal doxorubicin

Interventions

Trastuzumab and non-pegylated liposomal doxorubicin DRUG

3 Cohorts (3+3 design): Cohort 1- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (45 mg/m2) IV Cohort 2- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (50 mg/m2) IV Cohort 3- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV

Also known as: T-DM1 and non-pegylated liposomal doxorubicin

Experimental arm

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Patient able and willing to comply with protocol
• Cytologically or histologically confirmed carcinoma of the breast.
• Incurable locally advanced or metastatic disease who have previously received up to two previous chemotherapy regimens in this setting. Patient must have progressed or relapsed on or after taxane and trastuzumab-based therapy.
• HER2-positive disease
• At least one measurable lesion according to RECIST version 1.1; or patients with non measurable lesions could be included with these exceptions:
• o patients with only blastic bone lesions / with only pleural, peritoneal or cardiac effusion, or meningeal carcinomatosis
• ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Life expectancy ≥ 3 months
• Adequate bone marrow function:
• Hemoglobin ≥ 10 g/dl.
• Absolute neutrophil count ≥ 1.5 x 109/L.
• Platelets ≥ 100 x 109/L without transfusions within 21 days
• International normalized ratio (INR) \< 1.5 × the upper limit of normal (ULN).

You may not qualify if:

• Previous treatment with T-DM1 or anthracyclines
• More than two chemotherapeutic regimens for locally advanced incurable disease or metastatic disease
• Prior anti-cancer treatment with chemotherapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C), hormonal therapy or lapatinib within 7 days, prior trastuzumab within 21 days (7 days if weekly trastuzumab) or any other targeted therapy within the last 21 days prior to starting study treatment
• Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or mBC is not allowed if:
• The last fraction of radiotherapy has been administered within 21 days prior to first study drug administration (except for brain irradiation; at least 28 days will be required)
• More than 25% of marrow-bearing bone has been irradiated
• History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to the active substance or to any of the excipients of T-DM1 or non-pegylated liposomal doxorubicin
• Patients with central nervous system (CNS) involvement. However, patients with metastatic CNS tumors may participate in this trial if the patient is \> 4 weeks from radiotherapy completion, is clinically stable with respect to CNS tumor at the time of study entry and is not receiving steroid therapy for brain metastases
• Severe/uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Cardiopulmonary dysfunction
• Current peripheral neuropathy of Grade ≥ 3 per the NCI CTCAE, v4.0
• History of a decrease in LVEF to \< 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
• Prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was cured ≥ 5 years before first dose of study drug with no subsequent evidence of recurrence
• Current known active infection with HIV, hepatitis B, and/or hepatitis C virus
• Women who are pregnant or breast-feeding

Sponsors & Collaborators

• MedSIR: lead
• Roche Pharma AG: collaborator
• Experior: collaborator

Study Sites (4)

MedSIR investigative site

Paris, 75020, France

Location

MedSIR investigative site

Paris, 92210, France

Location

MedSIR investigative site

Barcelona, 00835, Spain

Location

MedSIR investigative site

Madrid, 08035, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Ado-Trastuzumab Emtansine

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; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Scientific director
• Organization: Medica Scientia Innovation Research (MEDSIR)

trialsregister.medsir@medsir.org

+34 93 221 41 35

Study Officials

• Javier Cortés, MD

  Hospital Ramon y Cajal, Madrid, Spain

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 17, 2015
• First Posted: September 29, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 23, 2022
• Results First Posted: January 18, 2022

Record last verified: 2021-10

Locations

ES (2); FR (2)