Molecular Profile of Breast Cancer in Ugandan Patients With Stage IIB-III Breast Cancer

NCT03518242 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: U025NCI-2018-02609RG10014038424
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the molecular profile of breast cancer in Ugandan patients with stage IIB-III breast cancer. Creating a molecular profile of breast cancer my help doctors learn more about biological factors associated with breast cancer in Ugandan patients with as well as measure the benefits of locally available diagnostic studies and the possibility of providing treatment via oral medication.

Conditions

Breast Cancer Female; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Invasive Breast Carcinoma; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (6)

• Distribution of molecular subtypes

  Will classify Ugandan women into four categories based on molecular subtypes: estrogen receptor (ER) negative (-)/progesterone receptor (PR) - /HER2 - (triple negative), ER-/PR-/HER positive (+) (HER2), ER+/PR+/HER2- (luminal A), and ER/PR+/HER2 + (luminal B) and compare to aggregate data from previously published data on a cohort of African-American women using chi square tests.

  Up to 9 months

• Sensitivity to polymerase chain reaction (PCR)

  Sensitivity, defined as the proportion of women with a particular receptor detected by PCR, among those women who had the receptor detected by immunohistochemistry (IHC), to polymerase chain reaction (PCR) will be estimated with 95% confidence intervals (CIs), using IHC as the gold standard. Will also calculate the percent agreement between PCR and IHC, and compute the kappa statistic with 95% CIs to assess receptor status agreement between reverse transcription (RT)-PCR and IHC.

  Up to 9 months

• Specificity of PCR

  Specificity, defined as the proportion of women with a receptor not detected by PCR, among women who did not have the receptor detected by IHC, to PCR will be estimated with 95% CIs, using IHC as the gold standard. Will also calculate the percent agreement between PCR and IHC, and compute the kappa statistic with 95% CIs to assess receptor status agreement between RT-PCR and IHC.

  Up to 9 months

• Patient adherence to treatment

  Patient adherence as the proportion of women completing 8 cycles of therapy compared to historical controls from the UCI cancer registry database using chi square tests

  Up to 168 days (8 cycles)

• Incidence of adverse events

  Will describe the extent of adverse events assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Will also compare patient adherence and adverse events using chi square tests and compare survival using log-rank tests.

  Up to 6 months

• Overall Survival

  Will use Kaplan-Meier methodology.

  Up to 1 year

Study Arms (1)

Treatment (Specimen collection, chemotherapy)

EXPERIMENTAL

SPECIMEN COLLECTION: Patients undergo collection of tumor tissue and peripheral blood samples for analysis via next generation sequencing to identify novel pathways in the pathogenesis of breast cancer. TREATMENT: Patients are invited to participate in a treatment study. Patients receive cyclophosphamide PO daily on days 1-21, methotrexate PO QD on days 1, 8, and 15, and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Capecitabine; Procedure: Biospecimen Collection

Interventions

Cyclophosphamide DRUG

Given PO

Also known as: Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclostin, Fosfaseron, Mitoxan, Neosar

Treatment (Specimen collection, chemotherapy)

Methotrexate DRUG

Given PO

Also known as: Abitrexate, Brimexate, Emtexate, Fauldexato, Ledertrexate, Medsatrexate, Methylaminopterin

Treatment (Specimen collection, chemotherapy)

Capecitabine DRUG

Given PO

Also known as: Xeloda

Treatment (Specimen collection, chemotherapy)

Biospecimen Collection PROCEDURE

Undergo biospecimen collection

Treatment (Specimen collection, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Women with any menopausal status, with newly diagnosed, locally advanced and histologically confirmed invasive breast cancer (Patients with stage 2B \[i.e. T3N0\], 3A, 3B, and 3C disease)
• Absolute neutrophil count (ANC) \> 1500/mm
• Hemoglobin \> 9 g/dL
• Platelets \>=100,000 cells/mm\^3
• Total bilirubin =\< 1.2 mg/dL
• International normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN
• Serum alkaline phosphatase should be 1.5 x ULN
• Patients with positive hepatitis B or C serologies without known active disease must meet the eligibility requirements for ALT, AST, total bilirubin, INR, activated partial thromboplastin time (aPTT), and alkaline phosphatase on at least two consecutive occasions, separated by at least 1 week
• Adequate renal function with serum creatinine \< 1.5 x ULN
• Premenopausal patients must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause
• Women of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment
• Left ventricular ejection fraction \>= 50%
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Signed written informed consent

You may not qualify if:

• A treatment-free interval of \< 6 months with previous chemotherapy
• Active, unresolved infection or systemic disease (e.g. pulmonary or metabolic disease)
• Patients with active liver disease
• Patients with active cardiac disease, including congestive heart failure (or therapy specifically for congestive heart failure \[CHF\])
• Patients with uncontrolled hypertension (diastolic \>100 mmHg or systolic \> 160 mmHg)
• Known hypersensitivity to any of the drugs
• Significant current illness (including psychiatric illness)
• Any social situations or other conditions that in the opinion of the investigator limit compliance with study requirements
• Calcium imbalance
• Patients that have received treatment with sorividine or brividine (herpex) or any related analogue within 4 weeks prior to starting the investigational product (IP)
• Eye problems
• Patients on any of the following medications: acitretin, azathioprine, Bacillus Calmette Guerin (BCG) (intravesicular), belimumab, deferiprone, diphyrone, etanercept, foscarnet, gimeracil, levetriracetam, natalizumab, pimercrolimus, retinoids, sulfazalazine, tacrolimus tofacitininb
• Patients receiving any anticoagulation (including warfarin)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

New Mulago Hospital

Kampala, 256, Uganda

Location

Uganda Cancer Institute

Kampala, 3935, Uganda

Location

MeSH Terms

Interventions

Cyclophosphamide; Methotrexate; Capecitabine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Manoj Menon

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2018
• First Posted: May 8, 2018
• Study Start: June 6, 2018
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2)