Advanced Triple Negative Breast Cancer (TNBC) With High TAMs Clinical Trial
— TNBCOfficial title:
A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
| Verified date | May 2021 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients
| Status | Completed |
| Enrollment | 50 |
| Est. completion date | March 23, 2020 |
| Est. primary completion date | January 4, 2020 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Nedlands | Western Australia |
| Austria | Novartis Investigative Site | Salzburg | |
| Austria | Novartis Investigative Site | Vienna | |
| Austria | Novartis Investigative Site | Vienna | |
| Belgium | Novartis Investigative Site | Bruxelles | |
| France | Novartis Investigative Site | Paris | |
| France | Novartis Investigative Site | Saint-Herblain Cédex | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Dresden | |
| Germany | Novartis Investigative Site | Essen | |
| Hong Kong | Novartis Investigative Site | Hong Kong SAR | |
| Italy | Novartis Investigative Site | Bologna | |
| Italy | Novartis Investigative Site | Napoli | |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Barcelona | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Santiago de Compostela | Galicia |
| Taiwan | Novartis Investigative Site | Taipei | |
| Turkey | Novartis Investigative Site | Istanbul | |
| United States | Massachusetts General Hospital Cancer Center SC | Boston | Massachusetts |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Australia, Austria, Belgium, France, Germany, Hong Kong, Italy, Korea, Republic of, Spain, Taiwan, Turkey,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment) | PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. | 4 years | |
| Secondary | Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau | AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days | day 21 (end cycle 1); day 84 (end cycle 4) | |
| Secondary | Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax | day 21 (end cycle 1); day 84 (end cycle 4) | ||
| Secondary | Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU) | day 21 (end cycle 1); day 84 (end cycle 4) | day 21, day 84 | |
| Secondary | AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU) | day 21 (end cycle 1); day 84 (end cycle 4) | day 21, day 84 | |
| Secondary | Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels | results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days. These Biomarker Analyses were performed for MCS110 treated patients only. | baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148 | |
| Secondary | Serum C-terminal Telopeptide of Type I Collagen (CTX-I) | results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days.
Biomarker Analyses performed for MCS110 treated patients only. |
baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148 | |
| Secondary | Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) | CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. | 4 years | |
| Secondary | Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response | CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. | 4 years | |
| Secondary | Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption | patients treated with MCS110 only | 4 years | |
| Secondary | MCS110 Dose Intensity | Relative dose intensity by categories.
Patients treated with MCS110 only. The dose intensity measures the dose actually taken versus the planned dose, and is expressed in percentage: <50%: less than 50 % of the planned dose received; 50-<75 %: dose received is 50% or more, but less than 75 %; 75-<90 %: dose received is 75% or more, but less than 90%; 90-<110 %: dose received is 90% or more, but less than 110% |
4 years | |
| Secondary | Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies. | results expressed as a the ratio change from baseline expressed in percentage: Biopsies were taken at baseline and between Day 29 and Day 43. Patients treated with MCS110 only | Baseline, Day 29-43 | |
| Secondary | Circulating Monocytes Cells in Blood | Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only. | day 15, 29, 43, 50 |