Open-label Study of Safety, Tolerability and Pharmacokinetics of Multiple Doses of BI-CON-02 in Patients With HER2-positive Metastatic Breast Cancer, Previously Treated With Trastuzumab

NCT03062007 | Terminated Phase 1 DMC

• 1 other identifier: ONC-BICON02-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief Summary

This study will evaluate the safety and tolerability of BI-CON-02 in patients with HER2-positive metastatic breast cancer, previously treated with trastuzumab The clinical trial protocol for BI-CON-02 prescribes a start dose of 0,3 mg/kg. After the Data and Safety Monitoring Committee evaluates the data of tolerability and safety of BI-CON-02, received during 3 weeks of investigational product therapy (Week 3, Day 1) and approves, extra doses can be used. Once the safety of investigational product is confirmed, the dose will be increased in the subsequent cohorts. Planned doses - 0,3 mg/kg; 0,6 mg/kg; 1,2 mg/kg; 2,4 mg/kg; 3,6 mg/kg and 4,8 mg/kg.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) Safety and tolerability of multiple doses of Safety and tolerability of multiple doses of BI-CON-02

  The number of patients with treatment-related AEs assessed by CTCAE, abnormal laboratory values and instrumental tests (ECG).

  Up to Week 55

• Maximum tolerated dose (MTD) or recommended dose (RD) of BI-CON-02

  MTD is defined as maximum dose at which DLT occurs in more than 1 patient of 6

  At Week 3 Day 1

Secondary Outcomes (6)

• Area under the plasma concentration versus time curve (AUC)

  Up to 55 weeks

• Immunogenetics of BI-CON-02

  Up to Week 55

• Peak Plasma Concentration (Cmax)

  Up to 55 weeks

• Elimination half-life (T1/2)

  Up to 55 weeks

• Volume of distribution at steady state (Vss)

  Up to 55 weeks

Study Arms (1)

BI-CON-02

EXPERIMENTAL

The start dose of BI-CON-02 will be 0,3 mg/kg and it will be possible to increase gradually BI-CON-02 doses up to 0,6 mg/kg; 1,2 mg/kg; 2,4 mg/kg; 3,6 mg/kg and 4,8 mg/kg for subsequent dose cohorts. A possibility to include a new dose cohort in the study will be considered by the Data and Safety Monitoring Committee, basing on the data of BI-CON-02 safety and tolerability, received at the Visit (Week 3, Day1) in the previous dose cohort (3 weeks after - 21st day of therapy).

Drug: BI-CON-02

Interventions

BI-CON-02 DRUG

BI-CON-02 prescribed as intravenous infusion once per 3 weeks. Investigational product therapy during 1 year (up to 18 cycles, duration of 21 days each).

BI-CON-02

Eligibility Criteria

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

You may qualify if:

• To participate in the clinical study, patients must comply to the following criteria:
• Signed patient's information sheet and informed consent form to participate in the study
• Females aged ≥ 18 years
• Histologically confirmed diagnosis of locally advanced or metastatic breast cancer.
• HER2-positive tumor status by results of immunohistochemistry (IHC3+) or hybridization in-situ (ISH), received at the local laboratory, experienced/certified to determine HER2 expression by means of accurate and validated methods.
• Disease progression during or after trastuzumab-based chemotherapy.
• Previous chemotherapy on metastatic breast cancer.
• Requirements for laboratory parameters determined below:
• Hematology: Absolute neutrophil count:
• Platelets:
• Hemoglobin: ≥ 1500/mm3 (1.5 x 109 cells/L)
• /mm3 (100 x 109 cells/L)
• g/dl
• Liver function: Total bilirubin:
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkalinephosphatase ≤ 1.5 x ULN

You may not qualify if:

• The patient will be considered ineligible for the study in case she has any criteria listed here below:
• Clinically significant cardiovascular diseases:
• Myocardial infarction within 6 months before screening
• Unstable angina within 3 months before screening
• Congestive heart failure Class III or IV according to the New York Heart Association (NYHA) criteria
• Clinically significant ventricular arrhythmia, that have to be treated, including ventricular tachycardia, ventricular fibrillation, history of cardiac arrest
• QTc interval \> 460 ms (ECG) (calculated according to Fredericia formula), or a diagnosis of long QTc syndrome
• Ejection fraction of left ventricle ≤ 50% (EchoCG)
• Hypotension (systolic arterial blood pressure \< 86 mm of mercury) or bradycardia with a heart rate of \< 50 beats per min., except when caused by medications (e.g. beta-blockers)
• Uncontrolled arterial hypertension (systolic arterial blood pressure \> 170 mm of mercury or diastolic arterial blood pressure \> 105 mm of mercury)
• Troponins I ≥ 0.2 ng/ml
• Patients with known cerebral metastases or clinical signs of cerebral metastases.
• Patients with severe dyspnea at rest, or those who need additional oxygen therapy in everyday life.
• History of hypersensitivity to trastuzumab ≥ 3 severity level
• History of any toxicity related to trastuzumab administration that resulted in the termination of trastuzumab therapy.

Sponsors & Collaborators

• Biointegrator LLC: lead

Study Sites (6)

3. State Medical Preventive Institution "Kirov Region Clinical Oncological Dispensary"

Kirov, 610021, Russia

Location

5. State Budgetary Public Healthcare Institution "Leningrad Region Oncological Dispensary", department of surgery

Leningrad Region Settlement Kuz'molovsky, 188663, Russia

Location

1. Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N.Blokhin" of the Russian Academy of Medical Sciences.

Moscow, 115478, Russia

Location

2. Moscow State Public Healthcare Institution "Moscow City Oncological Hospital #62 of the Moscow Public Healthcare Department"

Moscow Region, Krasnogorsk District, Settlement Istra, 143423, Russia

Location

6. State Budgetary Public Healthcare Institution of the Nizhni Novgorod Region "Nizhni Novgorod Region Oncological Dispensary"

Nizhny Novgorod, 603081, Russia

Location

4. State Budgetary Educational Institution of Higher Professional Education "Saint-Petersburg State Medical University n.a. academician I.P.Pavlov of the Federal Agency for Public Healthcare and Social Development"

Saint Petersburg, 197022, Russia

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 23, 2017
• Study Start: September 1, 2016
• Primary Completion: June 5, 2017
• Study Completion: June 5, 2017
• Last Updated: July 16, 2019

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6)