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

University of California Irvine (UCI)

Status and phase: Begins enrollment in 5 months; Phase 2; Phase 1

Conditions: Cognitive Impairment; Ovarian Cancer

Treatments: Other: Placebo; Drug: N-Acetyl-Cysteine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04520139

UCI 18-120 (Other Identifier)

20205846

Details and patient eligibility

About

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).

Enrollment: 102 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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102 participants in 2 patient groups

Phase 1 Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: N-Acetyl-Cysteine

Phase 2 Dose Expansion

Experimental group

Description:

Patients will be randomized to receive NAC at the maximum tolerated dose or placebo.

Treatment:

Other: Placebo

Drug: N-Acetyl-Cysteine