Triple Negative Breast Cancer
Conditions
Keywords
Neoadjuvant chemotherapy, Adjuvant chemotherapy, TNBC
Brief summary
The GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the adjuvant treatment of patients with high risk, early stage Globo-H Positive TNBC.
Interventions
DEVICEGlobo H IHC Assay
The Globo H IHC assay will be used to identify eligible patients who may clinically benefit from the OBI-822 treatment, defined by Globo H expression.
BIOLOGICALadagloxad simolenin combined with OBI-821
In the neoadjuvant and adjuvant phases of the study for a total of 100 weeks; subcutaneously injections.
OTHERStandard of care treatment
Standard of care treatment consisting of observation alone, adjuvant capecitabine or platinum monotherapy over a 100 week period.
Sponsors
OBI Pharma, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented radiographic and histopathologic confirmed primary localized invasive breast cancer. * Histologically documented TNBC (estrogen receptor negative \[ER-\]/progesterone receptor negative \[PR-\]/human epidermal growth factor 2 negative \[HER2-\]) defined as ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and negative HER2/neu- status, confirmed on tumor sample. * HER2/neu negative will be defined as one of the following criteria: * IHC 0 or 1+ * Single-probe average HER2 gene copy number of \<6 signals/nucleus * Dual-probe fluorescent in-situ hybridization (FISH) HER2/neu chromosome 17 (CEP17) non-amplified ratio of \<2 * Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site is not available) tumor obtained at time of definitive surgery or initial diagnosis (only if surgical tumor sample is not available). Globo H expression will be determined during pre-screening by Central lab. Instructions for submission of slides/tumor tissue blocks are provided in the protocol and study Lab Manual. * No evidence of metastatic disease in chest, abdomen and pelvis by CT or other adequate imagining during the Screening Phase. Imaging within 3 months prior to randomization is acceptable as baseline scan. Bone scans and imaging of the brain at screening is optional, and should be symptom directed. * High risk patients with no evidence of disease after completing standard treatment and meeting ONE of the following criteria: * Neoadjuvant chemotherapy followed by definitive surgery: Residual invasive disease following neoadjuvant chemotherapy defined as: A contiguous focus of residual invasive cancer in the surgical breast specimen measuring ≥1 cm in diameter and/or with residual invasive cancer in at least one axillary node (micrometastases or macrometastases), as determined by local pathology review. * Definitive surgery followed by adjuvant chemotherapy: Pathological Prognostic Stage IIB, Stage IIIA , Stage IIIB, or Stage IIIC disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. * Must have completed at least 4 cycles of a standard taxane and anthracycline-based multi-agent chemotherapy regimen (or a taxane-only regimen if the patient is ineligible for anthracycline treatment) either in the neoadjuvant or adjuvant setting (e.g., National Comprehensive Cancer Network recommended regimens):. * Randomization must occur (a) within 16 weeks after definitive surgery and radiation therapy (if radiation therapy administered) in patients who received neoadjuvant multiagent chemotherapy or, (b) for patients receiving adjuvant multiagent chemotherapy (not including capecitabine, immune checkpoint inhibitor), within 16 weeks after the completion of the adjuvant multiagent chemotherapy and radiation therapy (if radiation therapy administered). Note: patients may be randomized and initiate study treatment concurrent with adjuvant SOC therapy (observation, capecitabine, immune checkpoint inhibitor ± capecitabine). * Randomization must occur (a) within 16 weeks after definitive surgery and radiation therapy (if radiation therapy administered) in patients who received neoadjuvant multiagent chemotherapy or, (b) for patients receiving adjuvant multiagent chemotherapy (not including capecitabine, immune checkpoint inhibitor), within 16 weeks after the completion of the adjuvant multiagent chemotherapy and radiation therapy (if radiation therapy administered). Note: patients may be randomized and initiate study treatment concurrent with adjuvant SOC therapy (observation, capecitabine, immune checkpoint inhibitor ± capecitabine). * All treatment-related toxicities resolved to Grade \<1 on National cancer institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria (except hair loss and ≤Grade 2 neuropathy, which are acceptable). * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. * Females must be either of non-childbearing potential, i.e., surgically sterilized (have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months before the start of the trial and/or hysterectomy), or one year postmenopausal; or if of childbearing potential must have a negative pregnancy test (urine or serum) at screening. * Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire Treatment Phase and for at least 4 weeks (28 days) after the last dose of study treatment. * Adequate hematological, hepatic and renal function as defined below: * Absolute neutrophil count (ANC) ≥1,500/µL * Platelets ≥75,000/µL * Hemoglobin ≥8.5g/dL * Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥55 mL/min for subjects with creatinine levels \>1.5 × institutional ULN (glomerular filtration rate can also be used in place of creatinine or creatinine clearance may be calculated per institutional standard) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN * Alkaline Phosphatase (ALP) ≤2.5 × ULN * Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented) * Consent to participate with a signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved patient informed consent for the study prior to beginning any specific study procedures. * Ability to understand and willingness to complete all protocol required procedures.
Exclusion criteria
* Local recurrence of or previous history of ipsilateral or contralateral invasive breast cancer within 10 years prior to randomization \[for synchronous tumors see
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measuring the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease free survival (IDFS) in the study population. | 5 years | The outcome measure of the study is IDFS, defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of first invasive disease recurrence (local, regional or distant), the date of secondary primary invasive cancer (breast or not), or the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Overall Survival (OS). | 7 years | OS is defined as the time from randomization to date of death from any cause |
| Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Quality of Life (QoL). | 7 years | QoL defined as time to definitive deterioration in Health-related Quality of Life (HRQOL) using the global health status/QoL scale from European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L). QoL baseline established at randomization. Definitive deterioration defined as a 5% worsening relative to baseline in the HRQOL scale score from EORTC QLQ-C30 questionnaires with no subsequent improvement above threshold, scored with the EORTC QLQ-C30 v3.0 Scoring Manual. The EQ-5D-5L questionnaire assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, rated by the patient. It is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. 28 questions have a 4 point scale: not at all(1) to very much(4). 2 questions have a 7-point scale: very poor (1) to excellent(7). |
| Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Breast cancer-free interval (BCFI). | 7 years | BCFI is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first invasive disease recurrence (local, regional or distant), the date of ductal carcinoma in situ (ipsilateral or contralateral), or the date of death from breast cancer |
| Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Distant disease-free survival (DDFS). | 7 years | DDFS is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first distant disease recurrence, the date of the second primary invasive cancer (non-breast), or the date of death from any cause |
| Incidence and severity of adverse events (AEs) [Time Frame: AEs will be noted as it occurs, with a timeframe from beginning of randomization to 4 weeks after last dose of study treatment.] | 2 years | Adverse Events will be graded and recorded by investigators per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). |
Countries
Australia, Brazil, China, Hong Kong, Mexico, Peru, Poland, Russia, South Africa, South Korea, Taiwan, Ukraine, United States
Outcome results
None listed