Clinical trial NCT02435680: Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
Official title: A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
Keywords: MCS110; carboplatin; gemcitabine; TNBC; TAMs
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-05-06
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients


Eligibility criteria: Inclusion Criteria:

* Adult women (≥ 18 years of age) with advanced TNBC.
* Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based on last available tumor tissue.
* ER/PgR negativity to follow local guidelines
* If IHC HER2 2+, a negative FISH test is required
* A pre-treatment tumor biopsy demonstrating high TAM content as assessed per the central laboratory
* Patients must have:

At least one measurable lesion per RECIST 1.1. (Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an identifiable soft tissue component that meets the measurability criteria)

Exclusion Criteria:

* Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant chemotherapy is allowed (carboplatin, cisplatin or gemcitabine only if \> 12 months has passed since last administration).
* Therapy for underlying malignancy within 2 weeks prior to start of study treatment:
* Chemotherapy, biologic therapy (antibodies and biologically targeted small molecules)
* Radiotherapy
* Major surgery
* Patients receiving concomitant immunosuppressive agents or chronic corticosteroids (≥10 mg of prednisone or equivalent) at the time of first study dose.
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening.
* Known history of human immunodeficiency virus or active infection with hepatitis virus or any uncontrolled active systemic infection.
* Patients with the following laboratory values during screening and on Day 1 predose:
* Absolute Neutrophil Count (ANC) \< 1.5x109/L
* Hemoglobin \< 9 g/dL
* Platelets \< 100x109/L
* Serum creatinine \> 1.5 x ULN
* Serum total bilirubin \> 1.5 x ULN
* AST/SGOT and ALT/SGPT \> 3.0 x ULN

Primary outcomes:
measure: Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)
timeFrame: 4 years
Secondary outcomes:
measure: Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau
timeFrame: day 21 (end cycle 1); day 84 (end cycle 4)
measure: Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
timeFrame: day 21 (end cycle 1); day 84 (end cycle 4)
measure: Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
timeFrame: day 21, day 84
measure: AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
timeFrame: day 21, day 84
measure: Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels
timeFrame: baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
measure: Serum C-terminal Telopeptide of Type I Collagen (CTX-I)
timeFrame: baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
measure: Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)
timeFrame: 4 years
measure: Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response
timeFrame: 4 years
measure: Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption
timeFrame: 4 years
measure: MCS110 Dose Intensity
timeFrame: 4 years
measure: Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.
timeFrame: Baseline, Day 29-43
measure: Circulating Monocytes Cells in Blood
timeFrame: day 15, 29, 43, 50
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center SC
state: Massachusetts
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hong Kong SAR
country: Hong Kong
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: