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

NCT ID: NCT04159818

Last Updated: 2022-03-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-21
• Study Completion Date: 2026-12-15

Brief Summary

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

Detailed Description

In the first stage, 13 evaluable patients will be accrued per cohort. Evaluable is defined as: at least one administration of nivolumab and availability of paired biopsies for immunohistochemistry (for induction treatment cohorts pre-induction and pre-nivolumab biopsies).

If there are 1 or no responses observed in these 13 patients, the cohort will be stopped. Otherwise, 21 additional patients will be accrued for a total of 34.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control group

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: 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

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: 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

Intervention Type: DRUG

40mg/m2, weekly for two weeks

Low dose doxorubicin induction

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: 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

Low dose doxorubicin

Intervention Type: DRUG

15mg flat dose, weekly for 8 weeks

Interventions

Nivolumab

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

Intervention Type: DRUG

Cisplatin

40mg/m2, weekly for two weeks

Intervention Type: DRUG

Low dose doxorubicin

15mg flat dose, weekly for 8 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• 18 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marleen Kok, MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Locations

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Marleen Kok, MD

Role: CONTACT

m.kok@nki.nl

+3120 512 ext. 9111

Leonie Voorwerk, MD

Role: CONTACT

l.voorwerk@nki.nl

+3120 512 ext. 9111

Facility Contacts

Marleen Kok, MD

Role: primary

m.kok@nki.nl

+3120512 ext. 9111

Ingrid AM Mandjes, MSc

Role: backup

i.mandjes@nki.nl

+3120512 ext. 9111

Other Identifiers

N19TON

Identifier Type: -

Identifier Source: org_study_id