Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients

NCT04159818 | Recruiting Phase 2

• 1 other identifier: N19TON
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center non-blinded randomized multi-cohort non-comparative phase II trial with a Simon's two-stage design.

Conditions

Metastatic Breast Cancer

Keywords

Triple negative; Metastatic disease

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Time from randomization to date of first tumor progression

  assessed monthly until progression or date of death; median 12 months

Secondary Outcomes (5)

• Overall response rate

  assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months

• Clinical benefit rate

  assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months

• Overall survival

  assessed monthly until date of death; median 12 months

• Toxicity of all study regimens

  assessed until 100 days after of treatment end

• Progression Free Survival after 6 cycles

  time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months

Study Arms (3)

Control group

EXPERIMENTAL

no induction treatment, nivolumab 240 mg flat-dose, every 2 weeks

Drug: Nivolumab

Cisplatin induction

EXPERIMENTAL

Cisplatin 40mg/m2, weekly for two weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks

Drug: Nivolumab; Drug: Cisplatin

Low dose doxorubicin induction

EXPERIMENTAL

Low dose doxorubicin 15mg flat dose, weekly for 8 weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks

Drug: Nivolumab; Drug: Low dose doxorubicin

Interventions

Nivolumab DRUG

240 mg flat-dose, every 2 weeks. From 20 weeks onwards, nivolumab will be administered every 4 weeks with a flat-dose of 480 mg starting from week 20 onwards

Cisplatin induction; Control group; Low dose doxorubicin induction

Cisplatin DRUG

40mg/m2, weekly for two weeks

Cisplatin induction

Low dose doxorubicin DRUG

15mg flat dose, weekly for 8 weeks

Low dose doxorubicin induction

Eligibility Criteria

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

You may qualify if:

• Metastatic or incurable locally advanced triple negative breast cancer (ER \< 10%, HER2 IHC 0,1+ or 2+ with no amplification)
• Metastatic lesion accessible for histological biopsy
• years or older
• Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease. Treatment with low-dose doxorubicin in the palliative setting is not allowed.
• WHO performance status of 0 or 1
• Measurable or evaluable disease according to RECIST 1.1
• Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year
• Subjects with brain metastases are eligible if these are not symptomatic and free of progression of at least 4 weeks
• A maximum dosage of 360 mg/m2 of anthracyclines and no previous anthracycline-related cardiac toxicity. In case of radiation in the cardiac area, hypertension, diabetes mellitus or hypercholesterolemia, the left ventricular ejection fraction must be 50% or higher.
• Adequate bone marrow, kidney and liver function

You may not qualify if:

• uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
• known history of leptomeningeal disease localization
• history of having received other anticancer therapies within 2 weeks of start of the study drug
• history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (\>10 mgl daily prednisone equivalents) or chronic infections.
• prior treatment with immune checkpoint inhibitors.
• active other cancer
• history of uncontrolled serious medical or psychiatric illness
• current pregnancy or breastfeeding

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Cisplatin; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Marleen Kok, MD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marleen Kok, MD

CONTACT

+3120 512; m.kok@nki.nl

Leonie Voorwerk, MD

CONTACT

+3120 512; l.voorwerk@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Patients are randomized between experimental cohorts and a control cohort.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are randomized between experimental cohorts and a control cohort.

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 12, 2019
• Study Start: February 21, 2020
• Primary Completion: December 15, 2022
• Study Completion (Estimated): December 15, 2026
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

NL (1)