Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women
Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women
This phase II trial studies whether a prior germline predictor of taxane-induced peripheral neuropathy (TIPN) can help identify a subgroup of patients who are at higher risk of chemotherapy-induced peripheral neuropathy in African American patients with stages I-III breast cancer. The study also investigates whether docetaxel maybe work better than paclitaxel with regard to TIPN rate/severity and dose reductions.
PRIMARY OBJECTIVES:
I. Prospectively validate a prior germline predictor of TIPN using the Common Terminology Criteria for Adverse Events (CTCAE). Specifically, this study will demonstrate that patients with a high-risk TIPN genotype have significantly more grade 2-4 TIPN than patients with a low risk genotype.
SECONDARY OBJECTIVES:
I. Validate a prior germline predictor of TIPN using the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) neurotoxicity subscale in Arm A.
II. Compare grade 2-4 TIPN based on CTCAE between weekly paclitaxel (Arm A) versus (vs.) every three-week docetaxel (Arm B).
III. Prospectively confirm dose reductions due to TIPN are lower for every three-week docetaxel compared with weekly paclitaxel in a prospective cohort of patients of African ancestry.
IV. Prospectively confirm dose reductions due to any cause are lower for every three-week docetaxel compared with weekly paclitaxel in a prospective cohort of patients of African ancestry.
V. Assess the ability of the high-risk genotype to predict TIPN risk for docetaxel.
EXPLORATORY OBJECTIVES:
Correlative Study Objectives:
I. Identify novel markers of TIPN and elucidate the mechanism. II. Whole genome sequencing of germline blood to evaluate for additional predictors of TIPN.
III. Create induced pluripotent stem cell (iPSC) derived neurons from patient samples.
IIIa. Evaluate whether clinical findings can be mimicked in vitro. IIIb. Evaluate gene expression (ribonucleic acid [RNA] sequencing [seq]) and the epigenome at baseline versus after exposure in those prone to TIPN versus those not.
IV. Create a biorepository of patient derived samples for future translational research.
Patient-Reported Outcome Objectives:
I. Compare Grade 2-4 TIPN (moderate to life threatening) based on Patient Reported Outcomes (PRO)-CTCAE items between weekly paclitaxel (Arm A) vs. every three-week docetaxel (Arm B).
II. Prospectively compare FACT/GOG-NTX Health-Related Quality of Life (HRQoL) subscale, Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function version (v.)2 Short Form (SF) 10a, scores between every three-week docetaxel and weekly paclitaxel and between high risk and low risk genotypes (Arm A) in a cohort of African ancestry.
III. Compare the impact on financial toxicity (Comprehensive Score for Financial Toxicity [COST] scores) for every three-week docetaxel compared with weekly paclitaxel.
IV. Examine associations between social determinants of health (zip code, marital status, education, income & insurance status) and dose reductions and treatment discontinuation.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician?s discretion.
ARM B: Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician?s discretion.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Inclusion Criteria:
Patients must be women with a known stage I-III invasive breast cancer diagnosis. Registration must occur within 84 days from the date of diagnosis
Patients must be capable and willing to provide informed consent
Patients must have plans to receive either neoadjuvant or adjuvant:
Patients must self-identify their race as black, African American, or of African descent; patients may be of any ethnicity
Patients with a history of other cancers are eligible if they have not received prior taxane or platinum or vinca alkaloid therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patients must not be pregnant or lactating
Women of childbearing potential must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
Exclusion Criteria:
Jonesboro, Arkansas 72401, United States
Burbank, California 91505, United States
East China, Michigan 48054, United States
Grosse Pointe Woods, Michigan 48236, United States
Macomb, Michigan 48044, United States
Norton Shores, Michigan 49444, United States
Rochester Hills, Michigan 48309, United States
Warren, Michigan 48093, United States
West Branch, Michigan 48661, United States
Columbus, Mississippi 39705, United States
New Albany, Mississippi 38652, United States
East Norriton, Pennsylvania 19401, United States
Collierville, Tennessee 38017, United States
Port Arthur, Texas 77642, United States
American Fork, Utah 84003, United States
Spokane, Washington 99204, United States
Spokane, Washington 99218, United States
Spokane Valley, Washington 99216, United States
Yakima, Washington 98902, United States
Summit, Wisconsin 53066, United States