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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01138137
First received: June 3, 2010
Last updated: March 22, 2012
Last verified: March 2012

June 3, 2010
March 22, 2012
June 2010
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01138137 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer
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

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ovarian Carcinoma, Stage 3 or 4
  • Epithelial Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • 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

Experimental: All subjects
Interventions:
  • Drug: Paclitaxel
  • Drug: N-acetylcysteine
  • Drug: Cisplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
33
December 2015
December 2014   (final data collection date for primary outcome measure)

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.
Female
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01138137
OHSU-4229, 4229, SOL-08005-L
Yes
OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
Not Provided
Principal Investigator: Edward A Neuwelt, MD Knight Cancer Institute at Oregon Health & Science University
OHSU Knight Cancer Institute
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP