Evaluation of Hydroxychloroquine to Prevent CIPN

Sponsor

University of Arizona (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05689359

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Gynecologic Cancer Early-stage Breast Cancer Peripheral Neuropathy Chemotherapy-induced Peripheral Neuropathy	Drug: Hydroxychloroquine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Symptomatic CIPN [Throughout study completion, an average of 6 months]
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]
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 [Baseline and 12 weeks]
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]
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 [Baseline and 12 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.