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Docetaxel or Paclitaxel in Reducing Chemotherapy-Induced Peripheral Neuropathy in African American Patients With Stage I-III Breast Cancer

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ClinicalTrials.gov Identifier: NCT04001829
Recruitment Status : Recruiting
First Posted : June 28, 2019
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information
First Submitted Date  ICMJE June 19, 2019
First Posted Date  ICMJE June 28, 2019
Last Update Posted Date July 29, 2019
Actual Study Start Date  ICMJE June 27, 2019
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
Validation of a prior germline predictor of paclitaxel-induced peripheral neuropathy (Arm A) [ Time Frame: Baseline ]
Patients will be coded as having the event as long as grade 2-4 neuropathy based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 occurred at any time during the observation period. Patients without neuropathy or with maximum of grade 1 neuropathy during the whole observation period will be coded as having no event.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04001829 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Grade 2-4 taxane-induced peripheral neuropathy (TIPN) [ Time Frame: Up to 3 years post-registration ]
    Will be based on CTCAE between both Arm A versus (vs.) Arm.
  • Patient-related outcome (PRO)-based neurotoxicity [ Time Frame: Up to 3 years post-registration ]
    Will be assessed using the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) questionnaire. The FACT/GOG-Ntx neurotoxicity total score will be analyzed as a continuous variable. Linear mixed effect models with random intercept (repeated measures within single patients with unstructured covariance matrices) will be fit to estimate the average difference in FACT/GOG-Ntx neurotoxicity total score between high versus (vs.) low risk genotype groups in the paclitaxel arm. Time and patient and disease characteristics will be included as covariates in the linear mixed effect model. Genotype group-by-time interaction will be tested to see whether the difference between the two genotype groups depends on time. For comparison between arm A and arm B, the FACT/GOG-Ntx neurotoxicity total score change between the baseline and at end of treatment will be compared using two sample t test.
  • Health-related quality of life (HRQoL) between both arms [ Time Frame: Up to 3 years post-registration ]
    The HRQoL total score will be analyzed as a continuous variable and compared between low and high-risk genotypes groups of the paclitaxel arm, and between the paclitaxel arm and the docetaxel arm groups, using two-sample t tests. Multivariable linear mixed effect models will also be fit to evaluate the time trend of HRQoL and to estimate the average group difference in HRQoL after adjusting for other covariates. Group-by-time interaction will be tested to see whether the difference in HRQoL between groups depends on time.
  • Physical function between both arms [ Time Frame: Up to 3 years post-registration ]
    Will be measured using the (PROMIS) Physical Function version (v)2.0 Short From 10a. The PROMIS Physical Function T score will be analyzed as a continuous variable, and it will be compared between the two treatment arms (A&B) and for the high risk vs. low risk genotypes (in arm A) using two-sample t tests
  • Financial toxicity between both arms [ Time Frame: Up to 6 months post-registration ]
    Will be assessed using the Comprehensive Score for Financial Toxicity (COST) scores and compared using a two-sample t tests.
  • PRO-CTCAE scores of numbness, tingling, and general pain between both arms [ Time Frame: Up to 3 years post-registration ]
    Will present PRO-CTCAE scores for each attribute (frequency, severity and/or interference) separately and compare PRO-CTCAE severity (coded 0-4) with CTCAE grades for the corresponding time period.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 27, 2019)
  • Association between Social economic determinants of health and treatment completion [ Time Frame: Baseline ]
    Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with treatment completion per protocol
  • Social economic determinants of health and FACT-Ntx neurotoxicity scores [ Time Frame: Baseline ]
    Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx neurotoxicity scores
  • Association between social determinants of health and FACT-Ntx HRQoL scores [ Time Frame: Baseline ]
    Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx HRQoL scores
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Docetaxel or Paclitaxel in Reducing Chemotherapy-Induced Peripheral Neuropathy in African American Patients With Stage I-III Breast Cancer
Official Title  ICMJE Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women
Brief Summary This phase II trial studies how well docetaxel or paclitaxel work in reducing chemotherapy-induced peripheral neuropathy in African American patients with stages I-III breast cancer. Drugs used in chemotherapy, such as docetaxel and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving docetaxel or paclitaxel may work better than other methods in reducing chemotherapy-induced peripheral neuropathy in patients with breast cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. Prospectively validate a prior germline predictor of paclitaxel-induced peripheral neuropathy (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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Anatomic Stage I Breast Cancer AJCC v8
  • Anatomic Stage IA Breast Cancer AJCC v8
  • Anatomic Stage IB Breast Cancer AJCC v8
  • Anatomic Stage II Breast Cancer AJCC v8
  • Anatomic Stage IIA Breast Cancer AJCC v8
  • 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 I Breast Cancer AJCC v8
  • Prognostic Stage IA Breast Cancer AJCC v8
  • Prognostic Stage IB Breast Cancer AJCC v8
  • Prognostic Stage II Breast Cancer AJCC v8
  • Prognostic Stage IIA Breast Cancer AJCC v8
  • 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
Intervention  ICMJE
  • Drug: Docetaxel
    Given IV
    Other Names:
    • Docecad
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Drug: Paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Paclitaxel
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: 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.
    Interventions:
    • Drug: Docetaxel
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 27, 2019)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2023
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 must not have received prior taxane or prior/concurrent platinum therapy
  • Patients with a history of other cancers are eligible if they have not received prior taxane or platinum or vinca alkaloid therapy
  • Patients must not have pre-existing peripheral neuropathy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must not have a total bilirubin > upper limit of normal (ULN)
  • Patients must not 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04001829
Other Study ID Numbers  ICMJE EAZ171
NCI-2019-00266 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EAZ171 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
ECOG-ACRIN-EAZ171 ( Other Identifier: DCP )
EAZ171 ( Other Identifier: CTEP )
UG1CA189828 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
Study Sponsor  ICMJE ECOG-ACRIN Cancer Research Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Bryan P Schneider ECOG-ACRIN Cancer Research Group
PRS Account Eastern Cooperative Oncology Group
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP