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Evaluation of Hydroxychloroquine to Prevent CIPN

Primary Purpose

Breast Cancer, Gynecologic Cancer, Early-stage Breast Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Chemotherapy Induced Peripheral Neuropathy, Hydroxycloroquine, Diffusion Tensor Imaging, Breast Cancer, Gynecologic Cancer, Paclitaxel, Neoadjuvant chemotherapy

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Patients with stage 1-3 breast cancer or gynecological cancer treated with curative intent Age ≥ 21 years old No prior neurotoxic chemotherapies No other neurotoxic chemotherapies planned during paclitaxel treatment (i.e, platinum) Need to be treated with paclitaxel weekly x 12 doses as determined by their treating physician Be able to undergo MR Imaging Be willing to comply with scheduled visits, treatment plan, and MR imaging Adequate organ function as defined as: Hematologic: Absolute neutrophil count (ANC) ≥ 1500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Hepatic: Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN Renal: Estimated creatinine clearance (CrCl)≥ 50 mL/min by Cockcroft-Gault formula Exclusion Criteria: Stage IV cancer CTCAE neurological function > grade 1 at baseline Mental limitation that precludes understanding of or completion of questionnaires History of diabetes or other neurological disorders Preexisting peripheral neuropathy Prior exposure to neurotoxic chemotherapy Currently taking medication to treat or prevent neuropathy Have non-MRI compatible metallic objects on/in body Have metallic hardware in the lower extremity which is MR compatible however would create too much artifact for MR examination Pregnant or lactating patients. Women of childbearing potential and sexually active men must use an effective contraception method during rreatment and for three months after completing treatment. Patients of childbearing potential must have a negative serum or urine B-hCG pregnancy test at screening. History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity) or macular degeneration. QTc prolongation defined as a QTcF > 500 ms Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Sites / Locations

  • University of Arizona Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Addition of Hydroxychloroquine to paclitaxel

Arm Description

Hydroxychloroquine will be added to chemotherapy in patients with early stage (1-3) breast cancer and gynecological cancers.

Outcomes

Primary Outcome Measures

Symptomatic CIPN
The primary endpoint is symptomatic CIPN defined as increase in in FACT-GOG/Ntx-12 questionnaire score of greater than or equal to 3 points post-chemotherapy with hydroxychloroquine in combination with paclitaxel chemotherapy in patients with early-stage breast cancer or gynecologic malignancies.

Secondary Outcome Measures

Predicting Symptomatic CIPN: FA and ADC values derived from DTI
Baseline fractional anisotrophy (FA) and apparent diffusion coefficient (ADC) values derived from DTI will be used to predict symptomatic CIPN prior to starting and end of chemotherapy.
Predicting Symptomatic CIPN: change in FA and ADC
Change in mean FA and ADC prior to starting and end of chemotherapy will be calculated. The mean of the change in FA and ADC values with 95% confidence intervals will be estimated (post- minus pre- chemotherapy). The baseline values and the change of FA and ADC will be used to predict the development of symptomatic CIPN using logistic regression.
Predicting Symptomatic CIPN: baseline NF-L levels
Baseline level of neurofilament light chain (NF-L) will be used to predict symptomatic CIPN. The baseline values will be used to predict development of symptomatic CIPN using logistic regression.
Predicting Symptomatic CIPN: Changes in NF-L levels
Changes in NF-L levels with chemotherapy used to predict development of symptomatic CIPN. NF-L measures will be summarized across time and analyzed using linear mixed effects model.

Full Information

First Posted
January 9, 2023
Last Updated
July 21, 2023
Sponsor
University of Arizona
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1. Study Identification

Unique Protocol Identification Number
NCT05689359
Brief Title
Evaluation of Hydroxychloroquine to Prevent CIPN
Official Title
Phase 2, Single Center, Single Arm Study to Evaluate the Decrease in CIPN With the Addition of Hydroxychloroquine to Chemotherapy in Patients With Early Stage (1-3) Breast Cancer and Gynecological Cancers Treated With Curative Intent
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
The study is being done to research if hydroxychloroquine can prevent chemotherapy induced peripheral neuropathy. Certain chemotherapy drugs, like paclitaxel, are known to cause neuropathy which can impact quality of life. Currently, there are no options for preventing peripheral neuropathy. In addition, there are no useful methods to assess peripheral nerve damage. This study will also explore using a study MRI of patients' feet prior to starting chemotherapy and after they have completed chemotherapy to see if there is any difference in their nerve structure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Gynecologic Cancer, Early-stage Breast Cancer, Peripheral Neuropathy, Chemotherapy-induced Peripheral Neuropathy
Keywords
Chemotherapy Induced Peripheral Neuropathy, Hydroxycloroquine, Diffusion Tensor Imaging, Breast Cancer, Gynecologic Cancer, Paclitaxel, Neoadjuvant chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Addition of Hydroxychloroquine to paclitaxel
Arm Type
Experimental
Arm Description
Hydroxychloroquine will be added to chemotherapy in patients with early stage (1-3) breast cancer and gynecological cancers.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine will be administered at 600 mg po BID for 3 days prior to starting chemotherapy, continued during the course of chemotherapy, and for 7 days after chemotherapy.
Primary Outcome Measure Information:
Title
Symptomatic CIPN
Description
The primary endpoint is symptomatic CIPN defined as increase in in FACT-GOG/Ntx-12 questionnaire score of greater than or equal to 3 points post-chemotherapy with hydroxychloroquine in combination with paclitaxel chemotherapy in patients with early-stage breast cancer or gynecologic malignancies.
Time Frame
Throughout study completion, an average of 6 months
Secondary Outcome Measure Information:
Title
Predicting Symptomatic CIPN: FA and ADC values derived from DTI
Description
Baseline fractional anisotrophy (FA) and apparent diffusion coefficient (ADC) values derived from DTI will be used to predict symptomatic CIPN prior to starting and end of chemotherapy.
Time Frame
Baseline
Title
Predicting Symptomatic CIPN: change in FA and ADC
Description
Change in mean FA and ADC prior to starting and end of chemotherapy will be calculated. The mean of the change in FA and ADC values with 95% confidence intervals will be estimated (post- minus pre- chemotherapy). The baseline values and the change of FA and ADC will be used to predict the development of symptomatic CIPN using logistic regression.
Time Frame
Baseline and 12 weeks
Title
Predicting Symptomatic CIPN: baseline NF-L levels
Description
Baseline level of neurofilament light chain (NF-L) will be used to predict symptomatic CIPN. The baseline values will be used to predict development of symptomatic CIPN using logistic regression.
Time Frame
Baseline
Title
Predicting Symptomatic CIPN: Changes in NF-L levels
Description
Changes in NF-L levels with chemotherapy used to predict development of symptomatic CIPN. NF-L measures will be summarized across time and analyzed using linear mixed effects model.
Time Frame
Baseline and 12 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with stage 1-3 breast cancer or gynecological cancer treated with curative intent Age ≥ 21 years old No prior neurotoxic chemotherapies No other neurotoxic chemotherapies planned during paclitaxel treatment (i.e, platinum) Need to be treated with paclitaxel weekly x 12 doses as determined by their treating physician Be able to undergo MR Imaging Be willing to comply with scheduled visits, treatment plan, and MR imaging Adequate organ function as defined as: Hematologic: Absolute neutrophil count (ANC) ≥ 1500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Hepatic: Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN Renal: Estimated creatinine clearance (CrCl)≥ 50 mL/min by Cockcroft-Gault formula Exclusion Criteria: Stage IV cancer CTCAE neurological function > grade 1 at baseline Mental limitation that precludes understanding of or completion of questionnaires History of diabetes or other neurological disorders Preexisting peripheral neuropathy Prior exposure to neurotoxic chemotherapy Currently taking medication to treat or prevent neuropathy Have non-MRI compatible metallic objects on/in body Have metallic hardware in the lower extremity which is MR compatible however would create too much artifact for MR examination Pregnant or lactating patients. Women of childbearing potential and sexually active men must use an effective contraception method during rreatment and for three months after completing treatment. Patients of childbearing potential must have a negative serum or urine B-hCG pregnancy test at screening. History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity) or macular degeneration. QTc prolongation defined as a QTcF > 500 ms Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexia Demitsas
Phone
520-694-9089
Email
ademitsas@arizona.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Segar, MD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Evaluation of Hydroxychloroquine to Prevent CIPN

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