Evaluation of Hydroxychloroquine to Prevent CIPN

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Gynecologic Cancer; Peripheral Neuropathy; Chemotherapy-induced Peripheral Neuropathy; Early-stage Breast Cancer
• Intervention / Treatment: Drug: Hydroxychloroquine

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Addition of Hydroxychloroquine to paclitaxel; Hydroxychloroquine will be added to chemotherapy in patients with early stage (1-3) breast cancer and gynecological cancers.	Drug: Hydroxychloroquine; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Throughout study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	Baseline and 12 weeks
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.	Baseline
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.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Principal Investigator: Jennifer Segar, MD, University of Arizona

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Diffusion Tensor Imaging; Paclitaxel; Neoadjuvant chemotherapy; Gynecologic Cancer; Chemotherapy Induced Peripheral Neuropathy; Hydroxycloroquine
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neuromuscular Diseases; Breast Neoplasms; Peripheral Nervous System Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: STUDY00001721

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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