Effect of NAC on Preventing Chemo-Related Cognitive Impairments in Ovarian Ca Pts Treated W/ PBT

Study Overview
=================
Brief Summary
-----------------
This is a phase I, dose-escalation and phase II dose-expansion clinical trial determining the maximum tolerated dose (MTD) and safety and tolerability of adding N-Acetyl-Cysteine (NAC) to ovarian cancer patients who are receiving a platinum-based therapy (PBT). This study will investigate whether NAC will mitigate chemotherapy-related cognitive impairment (CRCI).

Official Title
-----------------
Phase I Dose-Escalating and Phase II Dose-Expansion Study of N-Acetyl-Cysteine (NAC) Administration to Ovarian Cancer Patients Receiving Platinum-Based Therapy (PBT) for the Mitigation of Chemotherapy-Related Cognitive Impairment (CRCI)

Conditions
-----------------
Ovarian Cancer, Cognitive Impairment

Intervention / Treatment
-----------------
* Drug: N-Acetyl-Cysteine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Post-menopausal females (as defined by lack of menstruation for 12 months or status post oophorectomy) Histologic or pathologic diagnosis of stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer Eastern Cooperative Oncology Group (ECOG) ≤2 Life expectancy > 1 year Status post cytoreductive surgery for ovarian cancer or with planned cytoreductive surgery if treated with neoadjuvant chemotherapy Prescribed a minimum of six cycles of platinum-based chemotherapy Adequate organ function as defined below: Hemoglobin > 9 g/dL Leukocytes >1,500/mcl Absolute Neutrophil Count > 1,000/mcL Platelets > 125,00/mcL total bilirubin Within normal institutional limits Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal Serum creatinine < 1.5 mg/dL. Exclusion Criteria: Prior history of any cancer (other than non-melanoma skin cancer) Chemotherapy, radiation therapy, or erythropoietin treatment within the last 6 months Prior severe head injury Has a history of dementia or other neurodegenerative disorders Has an uncontrolled, treatment-resistant depression or other severe psychiatric illnesses Presence of known brain metastases Has an active infection requiring treatment Known immunosuppressive disease Has active systemic autoimmune diseases such as lupus Receipt of systemic immunosuppressive therapy Known human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C Pregnant of breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1 will be a dose-escalating design. Phase 2 will be a randomized, double-blinded, placebo-controlled study design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Escalation<br>Patients will receive NAC beginning at Cohort 1. If, at a given dose, none of the 3 patients shows a dose-limiting toxicity during the first cycle of PBT, then the dose is escalated 1 step for subsequent subjects. If, at a given dose, only 1 of 3 shows a dose-limiting toxicity, then up to 3 additional participants will be enrolled at that dose.If, at a given dose, the first 2, or any 2 of 3 subjects show a dose-limiting toxicity, then the dose will be de-escalated 1 step for future participants. At a dose where enrollment is expanded to between 4 and 6, if only 1 of 6 subjects shows a dose-limiting toxicity, then the dose will be escalated 1 step for future participants. However, if 2 or more of 4, 5, or 6participants show a dose-limiting toxicity, then the dose will be reduced one step for future participants. The maximum tolerated dose is defined as the highest dose not requiring deescalation. This is the dose to be used for the NAC arm of Phase II study. | Drug: N-Acetyl-Cysteine<br>* Given PO<br>* Other names: NAC;|
| Experimental: Phase 2 Dose Expansion<br>Patients will be randomized to receive NAC at the maximum tolerated dose or placebo. | Drug: N-Acetyl-Cysteine<br>* Given PO<br>* Other names: NAC;Other: Placebo<br>* Given PO<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose of N-Acetyl-Cysteine in Ovarian Cancer Patients Receiving Platinum-Based Therapy | Determination of the maximum tolerated dose (MTD) will be utilized to evaluate the safety and tolerability of adding N-Acetyl-Cysteine (NAC) in ovarian cancer patients who are also receiving platinum-based therapy (PBT), using a Phase I, dose-escalating design. | From the start date of treatment until 6 months after removal of treatment due to toxicity, termination of study or withdrawal of treatment, whichever came first. | 
| Recommended Phase 2 Dose for NAC administered with PBT | Determination of the recommended Phase 2 dose (RP2D) will be utilized to evaluate the safety and tolerability of adding NAC to PBT. | From the start date of treatment until 6 months after removal of treatment due to toxicity, termination of study or withdrawal of treatment, whichever came first. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chemotherapy-Related Cognitive Impairments