Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02311907
First received: December 8, 2014
Last updated: December 19, 2014
Last verified: May 2013
  Purpose

This randomized phase III trial is studying glutathione to see how well it works in preventing peripheral neuropathy caused by paclitaxel and carboplatin in patients with ovarian cancer, fallopian tube cancer, and/or primary peritoneal cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as glutathione, may help prevent peripheral neuropathy caused by paclitaxel and carboplatin. It is not yet known whether glutathione is more effective than a placebo in preventing peripheral neuropathy.


Condition Intervention Phase
Chemotherapeutic Agent Toxicity
Neuropathy
Neurotoxicity Syndrome
Pain
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Cancer
Stage IIIA Primary Peritoneal Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Cancer
Stage IIIB Primary Peritoneal Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Cancer
Stage IIIC Primary Peritoneal Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Cancer
Stage IV Primary Peritoneal Cancer
Drug: Glutathione
Other: Placebo
Drug: Carboplatin
Drug: Paclitaxel
Other: Quality-of-Life Assessment
Other: Laboratory Biomarker Analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Paclitaxel/carboplatin (PC) induced peripheral neuropathy as assessed by EORTC QLQ-CIPN20 [ Time Frame: Up to 6 courses of therapy ] [ Designated as safety issue: No ]
    The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale. Generalized linear models (repeated measures analysis of variance [ANOVA] if data are complete) will be used to compare the CIPN between GSH and placebo arms.


Secondary Outcome Measures:
  • Percentage of patients with grade 2+ and grade 3+ paclitaxel/carboplatin-induced (PCI) peripheral neuropathy (PN) according to the CTCAE neuropathy scale [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A chi-square test or Fisher's exact test will be used to compare the proportion of grade 2+ and grade 3+ chemotherapy induced peripheral neuropathy (CIPN) at any time during or at the end of the TAXOL/CBDCA based chemotherapy between GSH and placebo arms.

  • Times to onset of CTCAE grade 2+ and grade 3+ PN [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier curve and log-rank test will be used to compare time to grade 2+ and grade 3+ CIPN between GSH and placebo arms.

  • Percentage of patients undergoing dose reductions secondary to PCI PN [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A chi-square test or Fisher's exact test will be used to compare the proportion of patients requiring chemotherapy dose reductions secondary to TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms.

  • Percentage of patients discontinuing PC chemotherapy secondary to PN [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A chi-square test or Fisher's exact test will be used to compare the proportion of patients stopping TAXOL/CBDCA secondary to peripheral neuropathy between GSH and placebo arms.

  • Toxicity profile of glutathione as assessed by CTCAE v4.0 [ Time Frame: Up to 1 year after completion of treatment ] [ Designated as safety issue: Yes ]
    Descriptive statistics (frequency and percentage) will be used to describe the toxicity profile of GSH. A Wilcoxon rank-sum test or Fisher's exact test will be applied for comparison of most frequent toxicities between GSH and placebo arms when appropriate.

  • Antitumor activity of PC as defined by recurrence-free (for patients without clinical evidence of disease) or progression-free (for patients with clinical evidence of disease) survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A log-rank test and a Kaplan-Meier curve will be used to compare the recurrence free survival between GSH and placebo arms.

  • Change in patient reported quality of life as assessed by FACT-O and patient daily-symptom questionnaires over time [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    Two-sample t-tests and Wilcoxon rank-sum tests will be applied to compare changes of neuropathy as measured by patient symptom log and quality of life as measured by FACT-O from baseline to the end of TAXOL/CBDCA.

  • Association between genetic variations and grade 2+ PCI PN [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Logistic regression models will be used to evaluate the association of genetic variations (i.e. SNPs) with the incidence of grade 2+ neuropathy.

  • Paclitaxel acute pain syndrome incidence and severity between GSH and placebo arms [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Descriptive statistics and graphical procedure will be used to describe TAXOL/CBDCA acute pain syndrome incidence/severity between GSH and placebo arms.


Enrollment: 286
Study Start Date: December 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (glutathione, carboplatin)
Patients receive glutathione IV over 15 minutes, paclitaxel* IV over 3 hours, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21-28 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Glutathione
Given IV
Other Names:
  • Glutham
  • GSH
  • TAD
Drug: Carboplatin
Given IV
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Laboratory Biomarker Analysis
Correlative studies
Placebo Comparator: Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 3 hours, and carboplatin IV over 30 minutes as in arm I.
Other: Placebo
Given IV
Other Name: PLCB
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • TAX
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Laboratory Biomarker Analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Scheduled to undergo treatment with TAXOL at 150-200 mg/m2 and CBDCA at area under the curve (AUC) = 5-7 every 21 or 28 days for at least 12 weeks; alternatively, paclitaxel can be prescribed at 80 mg/m2 weekly for at least 12 weeks, with the same CBDCA dose of AUC = 5-7 every 21 days; additional chemotherapy agents are allowed (bevacizumab, etoposide, etc) per physician discretion, as long as they are not known to be neurotoxic; Note: patients ideally will begin GSH therapy prior to their first dose of this chemotherapy, but must begin GSH therapy prior to their second dose of chemotherapy
  • Ability to sign informed consent and understand the nature of a placebo-controlled trial
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Ability to complete English language questionnaire(s) by themselves or with assistance
  • Life expectancy >= 6 months
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only, per clinician discretion
  • Willingness to provide blood specimens as required by the protocol
  • White blood cell (WBC) >= 3400
  • Absolute neutrophil count (ANC) >= 1500
  • Platelet (PLT) >= 100,000
  • Hemoglobin (HgB) > 10.0
  • Creatinine =< 1.5 x upper limit of normal (ULN)

Exclusion Criteria:

  • Pre-existing history of peripheral neuropathy > grade 1 (National Cancer Institute [NCI] CTCAE version [v] 4.0) due to any cause (e.g., chemotherapy, diabetes, alcohol, toxin, or heredity)
  • Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception
  • Prior TAXOL and/or CBDCA chemotherapy treatment (other than the current treatment regimen)
  • Concurrent use of any agent being used specifically to prevent or treat neuropathy, including but not limited to the following:

    • Gabapentin
    • Glutamine powder or glutamine tablets
    • Vitamin B6 or E
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02311907

  Show 392 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Loprinzi Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02311907     History of Changes
Obsolete Identifiers: NCT00979082
Other Study ID Numbers: NCI-2011-01965, NCI-2011-01965, CDR0000654097, N08CA, NCCTG-N08CA, NCCTG-N08CA, U10CA037404
Study First Received: December 8, 2014
Last Updated: December 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Neurotoxicity Syndromes
Ovarian Neoplasms
Peripheral Nervous System Diseases
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Chemically-Induced Disorders
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Nervous System Diseases
Neuromuscular Diseases
Ovarian Diseases
Peritoneal Diseases
Poisoning
Urogenital Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators

ClinicalTrials.gov processed this record on May 21, 2015