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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:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT02311907
First received: December 8, 2014
Last updated: January 5, 2017
Last verified: January 2017
  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: Carboplatin
Drug: Glutathione
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Placebo
Other: Quality-of-Life Assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, 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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Paclitaxel/Carboplatin (PC) Induced Peripheral Neuropathy as Assessed by EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer (EORTC), Quality of Life (QLQ), Chemotherapy Induced Peripheral Neuropathy 20 (CIPN20)). [ Time Frame: Every 28 day cycle, up to 6 cycles. ]
    The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale (higher scores indicated less symptoms and better quality of life). Generalized linear models (repeated measures analysis of variance [ANOVA] if data are complete) will be used to compare the CIPN between Glutathione (GSH) and placebo arms.


Secondary Outcome Measures:
  • Recurrence-free Survival (for Patients Without Clinical Evidence of Disease) [ Time Frame: Up to 1 year ]
    A log-rank test and a Kaplan-Meier curve will be used to compare the recurrence free survival between GSH and placebo arms (for ovarian/fallopian tube/primary peritoneal patients only).

  • Change in Patient Reported Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Patient Daily-symptom Questionnaires Over Time. [ Time Frame: Baseline to 1 year ]
    Quality of life was measured by FACT-O (on a 0 to 100 scale, higher scores represent better life quality) from baseline and at the end of TAXOL/CBDCA. The change in Quality of Life was calculated as the difference between baseline measure and end of treatment measure (with range from -100 to 100). A negative change represents a worsening in QOL from baseline to one year. Abbreviations used: Change from Baseline (chg from bsl)

  • Paclitaxel Acute Pain Syndrome Incidence and Severity Between GSH and Placebo Arms [ Time Frame: Up to 1 year ]
    Descriptive statistics will be used to describe TAXOL/CBDCA acute pain syndrome incidence/severity between GSH and placebo arms. Pain was scored on a scale from 0-10, where 0 = 'No aches or pains' and 10 = 'Aches or pains as bad as can be.'

  • Percentage of Patients Delaying PC Chemotherapy Secondary to PN [ Time Frame: Up to 1 year ]
    Patients delaying TAXOL/CBDCA secondary to peripheral neuropathy between GSH and placebo arms.

  • Percentage of Patients Undergoing Dose Reductions Secondary to PCI PN [ Time Frame: Up to 1 year ]
    Proportion of patients requiring chemotherapy dose reductions secondary to TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms.

  • Percentage of Patients With Grade 2+ and Grade 3+ Paclitaxel/Carboplatin-induced (PCI) Peripheral Neuropathy (PN) According to the Common Terminology Criteria for Adverse Events (CTCAE) Neuropathy Scale [ Time Frame: Up to 1 year ]
    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. Neuropathy scale has grades 1 through 5 (1-mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening and Grade 5 Death related to AE).

  • Times to Onset of CTCAE Grade 2+ PN [ Time Frame: Up to 1 year ]
    Compare time to grade 2+ CIPN between GSH and placebo arms.

  • Times to Onset of CTCAE Grade 3+ PN [ Time Frame: Up to 5 years from registration ]
    Time to grade 3+ CIPN between GSH and placebo arms.


Enrollment: 195
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 intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
Drug: Carboplatin
Given IV, over 30 minutes per planned chemotherapy regimen
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Glutathione
Given IV, over 15 minutes, immediately before chemotherapy administration
Other Names:
  • Glutham
  • GSH
  • Reduced Glutathione
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV, over 1 or 3 hours, per planned chemotherapy regimen
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Placebo Comparator: Arm II (placebo, paclitaxel)
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
Drug: Carboplatin
Given IV, over 30 minutes per planned chemotherapy regimen
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV, over 1 or 3 hours, per planned chemotherapy regimen
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Placebo
Given IV
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 390 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Charles Loprinzi Alliance for Clinical Trials in Oncology
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT02311907     History of Changes
Obsolete Identifiers: NCT00979082
Other Study ID Numbers: N08CA
NCI-2011-01965 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000654097
U10CA037404 ( US NIH Grant/Contract Award Number )
Study First Received: December 8, 2014
Results First Received: July 19, 2016
Last Updated: January 5, 2017

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

ClinicalTrials.gov processed this record on April 28, 2017