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

Sponsor

University of California, Irvine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04520139

Collaborator

Jarrow Formulas Inc (Industry)

102

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Cognitive Impairment	Drug: N-Acetyl-Cysteine Other: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Phase 1 will be a dose-escalating design. Phase 2 will be a randomized, double-blinded, placebo-controlled study designPhase 1 will be a dose-escalating design. Phase 2 will be a randomized, double-blinded, placebo-controlled study design

Masking:

Double (Participant, Investigator)

Masking Description:

Phase 1 will be open label. Phase 2 will be be double-blinded.

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Dose Escalation 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 Given PO Other Names: NAC Sustain NAC
Experimental: Phase 2 Dose Expansion Patients will be randomized to receive NAC at the maximum tolerated dose or placebo.	Drug: N-Acetyl-Cysteine Given PO Other Names: NAC Sustain NAC Other: Placebo Given PO

Arm

Intervention/Treatment

Experimental: Phase 1 Dose Escalation

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

Given PO

Other Names:

NAC Sustain

NAC

Experimental: Phase 2 Dose Expansion

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

Drug: N-Acetyl-Cysteine

Given PO

Other Names:

NAC Sustain

NAC

Other: Placebo

Given PO

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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:

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of California, Irvine
Jarrow Formulas Inc

Investigators

Principal Investigator: Daniela Bota, MD, PhD, Chao Family Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Daniela A. Bota, Associate Professor, University of California, Irvine

ClinicalTrials.gov Identifier:

NCT04520139

Other Study ID Numbers:

UCI 18-120 [HS# 2020-5846]
2020-5846

First Posted:

Aug 20, 2020

Last Update Posted:

Oct 4, 2021

Last Verified:

Sep 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Daniela A. Bota, Associate Professor, University of California, Irvine

Additional relevant MeSH terms:

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cognitive Dysfunction

Acetylcysteine

N-monoacetylcystine

Study Results

No Results Posted as of Oct 4, 2021