Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women
概览
- 阶段
- 2 期
- 干预措施
- Questionnaire Administration
- 疾病 / 适应症
- Prognostic Stage IIIC Breast Cancer AJCC v8
- 发起方
- ECOG-ACRIN Cancer Research Group
- 入组人数
- 249
- 试验地点
- 952
- 主要终点
- Percentage of Participants With Grade 2-4 Taxane-Induced Peripheral Neuropathy (TIPN) by Genotype Risk Group in Arm A
- 状态
- 进行中（未招募）
- 最后更新
- 11天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm A (paclitaxel)
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.
干预措施: Questionnaire Administration
Arm A (paclitaxel)
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.
干预措施: Quality-of-Life Assessment
Arm B (docetaxel)
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.
干预措施: Quality-of-Life Assessment
Arm B (docetaxel)
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.
干预措施: Questionnaire Administration
Arm A (paclitaxel)
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.
干预措施: Paclitaxel
Arm B (docetaxel)
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.
干预措施: Docetaxel
结局指标
主要结局
Percentage of Participants With Grade 2-4 Taxane-Induced Peripheral Neuropathy (TIPN) by Genotype Risk Group in Arm A
时间窗: assessed at baseline, an end of each cycle, at 6 months and 1 year post registration
Grade 2-4 TIPN was assessed by treating physician using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patients who started protocol therapy on arm A (paclitaxel) were included in the analysis. The percentage of participants with grade 2-4 TIPN was calculated based on binomial distribution and was compared between high-risk vs low-risk genotype groups using Fisher exact test. Genotype risk group (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
次要结局
- Patient-Reported Neuropathy Score Change Between Baseline and End of Treatment by Genotype Risk Group in Patients on Arm A(assessed at baseline and at end of treatment, an average of 3 months)
- Percentage of Participants With Grade 2-4 TIPN Based on CTCAE Between Arm A and Arm B(assessed at baseline, an end of each cycle, at 6 months and 1 year post registration)
- Percentage of Participants With Dose Reduction Due to TIPN Between Arm A and Arm B(Dose reduction due to TIPN was assessed at end of each cycle, up to 4 cycles in arm A and 6 cycles in arm B)
- Percentage of Participants With Dose Reduction Due to Any Reason Between Arm A and Arm B(Dose reduction due to any reason was assessed at end of each cycle, up to 4 cycles in arm A and 6 cycles in arm B)
- Percentage of Participants With Grade 2-4 TIPN by Genotype Risk Group in Arm B(assessed at baseline, at end of each cycle, at 6 months and 1 year post registration)