Evaluation of Hydroxychloroquine to Prevent CIPN

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer, Gynecologic Cancer, Early-stage Breast Cancer, Peripheral Neuropathy, Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy Induced Peripheral Neuropathy, Hydroxycloroquine, Diffusion Tensor Imaging, Breast Cancer, Gynecologic Cancer, Paclitaxel, Neoadjuvant chemotherapy