Nivolumab After Induction Treatment in Triple-negative Breast Cancer (TNBC) Patients

NCT ID: NCT02499367

Last Updated: 2022-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2025-08-31

Brief Summary

This is a single center non-blinded randomized non-comparative phase II trial. The first stage of the trial consists of five arms ( with induction treatment followed by nivolumab, 1 with no induction treatment before nivolumab).

For the second stage, the number of arms will be reduced based on the results obtained in the first stage.

Detailed Description

Triple negative breast cancer (TNBC) patients have a relatively high relapse rate and upon relapse the median overall survival is less than a year. No targeted therapies are currently available for this subgroup. Compared to other breast cancer subtypes, the percentage of tumor-infiltrating lymphocytes (TILs) is significantly higher in TNBC. Given the durable responses induced by the immune checkpoint inhibitor nivolumab in other advanced solid cancers, immunotherapeutic approaches, such as blockade of PD-1 by nivolumab may be the key to treat TNBC. Moreover, since classical anticancer agents can stimulate immune effector cells, the investigators hypothesize that short-term induction treatment with radiation, doxorubicin, cyclophosphamide or cisplatin induces an anticancer immune response resulting in synergistic activity with nivolumab.

Conditions

Breast Cancer

Study Design

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

Study Groups

Radiation therapy

Radiotherapy on metastatic lesion

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Radiation therapy

Intervention Type: RADIATION

20 Gy to metastatic lesion

Low dose doxorubicin

15mg flat dose, once weekly for 2 weeks

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Low dose doxorubicin

Intervention Type: DRUG

15 mg flat dose, once weekly for 2 weeks

Cyclophosphamide

metronomic schedule, 50mg daily orally for 2 weeks

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Cyclophosphamide

Intervention Type: DRUG

metronomic schedule, 50 mg daily orally for 2 weeks

Cisplatin

40mg/m2, weekly for 2 weeks

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Cisplatin

Intervention Type: DRUG

40 mg/m2, weekly for 2 weeks

No induction treatment

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Interventions

Nivolumab

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Intervention Type: DRUG

Radiation therapy

20 Gy to metastatic lesion

Intervention Type: RADIATION

Low dose doxorubicin

15 mg flat dose, once weekly for 2 weeks

Intervention Type: DRUG

Cyclophosphamide

metronomic schedule, 50 mg daily orally for 2 weeks

Intervention Type: DRUG

Cisplatin

40 mg/m2, weekly for 2 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Metastatic triple negative breast cancer with confirmation of Estrogen Receptor (ER) and HER2 negativity on a histological biopsy of a metastatic lesion
• 18 years or older
• Metastatic lesion accessible for histological biopsy (Mandatory biopsies: pre-induction treatment, post-induction treatment, 6-weeks. Optional biopsies: 12-weeks, at progression, of irradiated site). The pre-induction treatment biopsy has to contain sufficient tumor content (≥100 tumor cells); subjects with samples that have insufficient tumor content will require re-biopsy prior to induction treatment. Interval between last treatment and pre-induction biopsy has to be at least 14 days
• One, two or three line(s) of chemotherapy for metastatic disease and with progression of disease on last treatment regimen
• Evaluable disease according to RECIST 1.1
• Metastatic lesion accessible for radiation with 1x20 Gray or 3x8 Gray
• Subjects with brain metastases are eligible if these are not symptomatic. Subjects who received prior treatment for brain metastases should be free of progression on magnetic resonance imaging (MRI) for at least 4 weeks after treatment is completed and prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• WHO performance status of 0 or 1
• Adequate bone marrow function
• Adequate hepatic function
• Adequate renal function
• Signed written informed consent

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 an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody
• live vaccine within 30 days of planned start of study therapy.
• active other cancer
• positive test for hepatitis B surface virus surface antigen (HBsAg) or hepatitis
• history of uncontrolled serious medical or psychiatric illness
• any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• 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

Antoni van Leeuwenhoek

Locations

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

N15TON

Identifier Type: -

Identifier Source: org_study_id