N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer - Full Text View

Sponsor:	OHSU Knight Cancer Institute
Information provided by (Responsible Party):	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT01138137

Purpose

RATIONAL FOR STUDYING IV NAC AS POTENTIAL CHEMOPROTECTANT:

Cisplatin has shown efficacy in the treatment of subjects with epithelial ovarian cancer. Systemic toxicities associated with cisplatin include nephro, oto, and nerve toxicities. It may be possible to reduce the toxicities of cisplatin by administering it in conjunction with IV NAC. NAC may reduce cisplatin related nephro, oto, and nerve toxicities without compromising the effectiveness of the chemotherapy against the ovarian cancer cells. It is possible that this combination of drugs may in the future allow ovarian cancer patients to receive the full series of IP cisplatin-paclitaxel chemotherapy, with fewer side effects and improved survival.

It is hypothesized that the proposed treatment of stage III or IV epithelial ovarian cancer with IP cisplatin and IV/IP paclitaxel in conjunction with IV NAC will limit the neurotoxicity, nephrotoxicity and ototoxicity that is associated with cisplatin administration.

Condition	Intervention	Phase
Ovarian Carcinoma, Stage 3 or 4 Epithelial Ovarian Carcinoma Primary Peritoneal Carcinoma	Drug: Paclitaxel Drug: N-acetylcysteine Drug: Cisplatin	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Dose Escalation Study of N-acetylcysteine (NAC) Administered Intravenously (IV) in Conjunction With Intraperitoneal (IP) Administered Cisplatin and IV/IP Paclitaxel in Patients With Stage III or IV Ovarian Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Cisplatin Paclitaxel Acetylcysteine

U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:

To determine the MTD and assess the toxicity of IV NAC [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
The MTD of IV NAC will be defined as one dose level below that which produces NCI CTC grade 3 or 4 non-hematologic toxicity in 20% of subjects. The toxicity of NAC can be differentiated from that of the chemotherapeutic drugs as the half-life of NAC is very short and adverse effects are seen either during or very soon after the administration of NAC.

Secondary Outcome Measures:

To describe tumor response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
To describe the incidence and severity of nephrotoxicity [ Time Frame: 4 years ] [ Designated as safety issue: No ]
To describe the incidence and severity of hearing loss [ Time Frame: 4 years ] [ Designated as safety issue: No ]
To describe the incidence and severity of peripheral and autonomic neuropathy [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	June 2010
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: All subjects	Drug: Paclitaxel Dose: 135mg/m2 infused IV on Day 1 of 3 week cycle Dose: 60mg/m2 infused IP on Day 8 of 3 week cycle 6 treatment cycles Drug: N-acetylcysteine A group of 5 subjects will be evaluated at each dose level. On Day 2 of each 3 week cycle, subject receives IV NAC followed by IP cisplatin. 6 treatment cycles Dose escalation schema: Level 1: 150mg/kg Level 2: 300mg/kg Level 3: 600mg/kg Level 4: 800mg/kg Level 5: 1000mg/kg Level 6: 1200mg/kg Other Name: NAC Drug: Cisplatin Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion 6 treatment cycles

Arms

Assigned Interventions

Experimental: All subjects

Drug: Paclitaxel

Dose: 135mg/m2 infused IV on Day 1 of 3 week cycle

Dose: 60mg/m2 infused IP on Day 8 of 3 week cycle

6 treatment cycles

Drug: N-acetylcysteine

A group of 5 subjects will be evaluated at each dose level.

On Day 2 of each 3 week cycle, subject receives IV NAC followed by IP cisplatin.

6 treatment cycles

Dose escalation schema:

Level 1: 150mg/kg

Level 2: 300mg/kg

Level 3: 600mg/kg

Level 4: 800mg/kg

Level 5: 1000mg/kg

Level 6: 1200mg/kg

Other Name: NAC

Drug: Cisplatin

Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion

6 treatment cycles

Detailed Description:

OBJECTIVES:

PRIMARY:

To determine the Maximum Tolerated Dose (MTD) and assess the toxicity of IV NAC in conjunction with IP cisplatin and IV/IP paclitaxel in subjects with stage 3 or 4 epithelial ovarian cancer that has been surgically debulked

SECONDARY:

To describe tumor response in subjects receiving treatment for previously debulked stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel , and IV NAC.
To describe the incidence and severity of nephrotoxicity ( Creatinine Clearance [CrCl]) in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV paclitaxel and IV NAC and who have had their disease surgically debulked.
To describe the incidence and severity of hearing loss in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel and IV NAC and who have had their disease surgically debulked.
To describe the incidence and severity of peripheral and autonomic neuropathy in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP Taxol and IV NAC and who have had their disease surgically debulked.

OUTLINE:

Subjects will undergo chemotherapy for epithelial ovarian cancer with paclitaxel IV, 135 mg/m2 (Day 1) and IP cisplatin 100 mg/m2 (Day2), followed by Taxol IP, 60 mg/m2 (Day 8) every 3 weeks for 6 courses. Sixty minutes prior to each course of IP cisplatin, IV NAC (starting at 150 mg/kg) will be infused over 30 minutes. A dose escalation schema for NAC will be followed. Toxicity to the therapy will be graded according to the Common Terminology Criteria for Adverse Events.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed written informed consent in accordance with institutional guidelines
Histologically confirmed diagnosis of stage 3 or 4 epithelial ovarian or primary peritoneal carcinoma
Have had debulking surgery with optimal tumor cytoreduction
Standard treatment offered for ovarian cancer including systemic or intraperitoneal cisplatin with systemic taxane-based chemotherapy
Age ≥ 18 years to ≤ 75 years
Laboratory testing within 14 days of registration:
- White blood cell count ≥ 2.5 x 103/mm3
- Absolute granulocyte count ≥ 1.2 x 103/mm3
- Platelets ≥ 100 x 103/mm3
- Creatinine < 1.8
- Bilirubin < 2.0
- SGOT/SGPT < 2.5 x institutional upper limits of normal
Performance status must be ECOG < 2 (Karnofsky ≥ 50)
Life expectancy of ≥ 60 days from the date of registration

Exclusion Criteria:

Pregnant, positive beta hCG, or lactating
History of clinically significant reactive airway disease
Active significant cardiac disease as evidenced by New York Heart Association Classification for CHF, Class III or IV
Uncontrolled (over the last 30 days) clinically significant confounding medical conditions
Allergies or other contraindications to IP cisplatin, IV Taxol, or IV NAC.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01138137

Contacts

Contact: Edward A Neuwelt, MD	503-494-5626	neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA	503-494-5626	hedrickn@ohsu.edu

Locations

United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA 503-494-5626 hedrickn@ohsu.edu
Principal Investigator: Edward A Neuwelt, MD

Sponsors and Collaborators

OHSU Knight Cancer Institute

Investigators

Principal Investigator:

Edward A Neuwelt, MD

Knight Cancer Institute at Oregon Health & Science University

More Information

No publications provided

Responsible Party:	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT01138137 History of Changes
Other Study ID Numbers:	OHSU-4229, 4229, SOL-08005-L
Study First Received:	June 3, 2010
Last Updated:	September 22, 2011
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:

ovarian cancer
epithelial ovarian cancer
peritoneal cancer

Additional relevant MeSH terms:

Carcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Acetylcysteine

N-monoacetylcystine
Cisplatin
Paclitaxel
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on February 09, 2012