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

NCT02499367 | Unknown Phase 2 DMC

• 1 other identifier: N15TON
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

triple negative; metastatic

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Time from randomization todate of first tumor progression

  assessed monthly until progression; median 12 months

Secondary Outcomes (3)

• Overall response rate

  At 12 weeks and 6 months

• Clinical benefit rate

  At 6 months

• Toxicity of all study regimens

  assessed until 100 days after of treatment end

Study Arms (5)

Radiation therapy

ACTIVE COMPARATOR

Radiotherapy on metastatic lesion

Drug: Nivolumab; Radiation: Radiation therapy

Low dose doxorubicin

ACTIVE COMPARATOR

15mg flat dose, once weekly for 2 weeks

Drug: Nivolumab; Drug: Low dose doxorubicin

Cyclophosphamide

ACTIVE COMPARATOR

metronomic schedule, 50mg daily orally for 2 weeks

Drug: Nivolumab; Drug: Cyclophosphamide

Cisplatin

ACTIVE COMPARATOR

40mg/m2, weekly for 2 weeks

Drug: Nivolumab; Drug: Cisplatin

No induction treatment

ACTIVE COMPARATOR

Drug: Nivolumab

Interventions

Nivolumab DRUG

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

Cisplatin; Cyclophosphamide; Low dose doxorubicin; No induction treatment; Radiation therapy

Radiation therapy RADIATION

20 Gy to metastatic lesion

Radiation therapy

Low dose doxorubicin DRUG

15 mg flat dose, once weekly for 2 weeks

Low dose doxorubicin

Cyclophosphamide DRUG

metronomic schedule, 50 mg daily orally for 2 weeks

Cyclophosphamide

Cisplatin DRUG

40 mg/m2, weekly for 2 weeks

Cisplatin

Eligibility Criteria

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

You may qualify if:

• Metastatic triple negative breast cancer with confirmation of Estrogen Receptor (ER) and HER2 negativity on a histological biopsy of a metastatic lesion
• 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

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 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.

Sponsors & Collaborators

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

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• Lin AY, Isaeva OI, Deger T, Geurts VCM, Vessies DCL, Voorwerk L, Slagter M, Moore KS, van der Leest P, Martens JWM, van den Broek D, Wessels LFA, Kok M. CfDNA-based copy-number dynamics during anti-PD1 treatment in metastatic triple negative breast cancer. Cell Rep Med. 2025 Dec 16;6(12):102512. doi: 10.1016/j.xcrm.2025.102512.

  PMID: 41406937 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Radiotherapy; Doxorubicin; Cyclophosphamide; Cisplatin

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; Therapeutics; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Marleen Kok, MD

  Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 16, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2023
• Study Completion: August 1, 2025
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

NL (1)