Taxane and Taxane-Induced Peripheral Neuropathy in African American Patients With Stage I-III Breast Cancer

ECOG-ACRIN Cancer Research Group

Status and phase: Active, not recruiting; Phase 2

Conditions: Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Invasive Breast Carcinoma; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8

Treatments: Drug: Docetaxel; Other: Questionnaire Administration; Other: Quality-of-Life Assessment; Drug: Paclitaxel

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT04001829

NCI-2019-00266 (Registry Identifier)

ECOG-ACRIN-EAZ171 (Other Identifier)

UG1CA189828 (U.S. NIH Grant/Contract)

EAZ171 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 249 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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:

  • Every 3-week docetaxel x 4-6 cycles OR
  • Weekly paclitaxel x 4 cycles
  • NOTE: Recommended therapies for various therapy regimens are outlined based on estrogen receptor (ER)/progesterone receptor (PR)/HER2 and nodal status. Where there are options, the treating physician will choose a regimen best fitted for that patient. If the physician does not feel any of the regimens are the best fit for the patient, the patient should not be enrolled. Physicians will also document why a regimen was felt to be inappropriate when an option

• 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

  • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
  • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• 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

• Patients have received prior taxane or prior/concurrent platinum therapy
• Patients have pre-existing peripheral neuropathy
• Patients have a total bilirubin > upper limit of normal (ULN)
• Patients have aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above 1.5 times the ULN concomitant with alkaline phosphatase above 2.5 times the ULN

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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249 participants in 2 patient groups

Arm A (paclitaxel)

Experimental group

Description:

Patients receive paclitaxel 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.

Treatment:

Other: Quality-of-Life Assessment

Drug: Paclitaxel

Other: Questionnaire Administration

Arm B (docetaxel)

Experimental group

Description:

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.

Treatment:

Other: Quality-of-Life Assessment

Other: Questionnaire Administration

Drug: Docetaxel