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

Phase 1

Not yet recruiting

• Conditions: Ovarian Cancer; Cognitive Impairment
• Interventions: Drug: N-Acetyl-Cysteine; Other: Placebo

• Registration Number: NCT04520139
• Lead Sponsor: University of California, Irvine

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-17
• Study First Submitted QC: 2020-08-17
• Study First Posted: 2020-08-20
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Study Start: 2025-12
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 102

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:

  1. Hemoglobin > 9 g/dL
  2. Leukocytes >1,500/mcl
  3. Absolute Neutrophil Count > 1,000/mcL
  4. Platelets > 125,00/mcL
  5. total bilirubin Within normal institutional limits
  6. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal
  7. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase 2 Dose Expansion	Placebo	Patients will be randomized to receive NAC at the maximum tolerated dose or placebo.
Phase 1 Dose Escalation	N-Acetyl-Cysteine	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.
Phase 2 Dose Expansion	N-Acetyl-Cysteine	Patients will be randomized to receive NAC at the maximum tolerated dose or placebo.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of N-Acetyl-Cysteine in Ovarian Cancer Patients Receiving Platinum-Based Therapy	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.	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.
Recommended Phase 2 Dose for NAC administered with 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.	Determination of the recommended Phase 2 dose (RP2D) will be utilized to evaluate the safety and tolerability of adding NAC to PBT.