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 is ongoing, but not recruiting participants.
Sponsor:
North Central Cancer Treatment Group
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00979082
First received: September 16, 2009
Last updated: December 13, 2011
Last verified: December 2011
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Purpose
RATIONALE: 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.
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chemotherapeutic Agent Toxicity Fallopian Tube Cancer Neurotoxicity Ovarian Cancer Pain Peripheral Neuropathy Primary Peritoneal Cavity Cancer |
Drug: carboplatin Drug: glutathione Drug: paclitaxel Other: placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: Double-Blind 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:
Genetics Home Reference related topics:
Charcot-Marie-Tooth disease
hereditary neuropathy with liability to pressure palsies
U.S. FDA Resources
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Paclitaxel/carboplatin (PC)-induced (PCI) peripheral neuropathy (PN) as assessed by EORTC QLQ-CIPN20 [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Percentage of patients with grade 2+ and grade 3+ PCI PN according to the CTCAE neuropathy scale [ Designated as safety issue: No ]
- Times to onset of CTCAE grade 2+ and grade 3+ PN [ Designated as safety issue: No ]
- Percentage of patients undergoing dose reductions secondary to PCI PN [ Designated as safety issue: No ]
- Percentage of patients discontinuing PC chemotherapy secondary to PN [ Designated as safety issue: No ]
- Toxicity profile of glutathione as assessed by CTCAE v4.0 [ Designated as safety issue: Yes ]
- 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 [ Designated as safety issue: No ]
- Patient reported quality of life as assessed by FACT-O and patient daily-symptom questionnaires over time [ Designated as safety issue: No ]
- Association between genetic variations and grade 2+ PCI PN [ Designated as safety issue: No ]
- Paclitaxel acute pain syndrome incidence and severity [ Designated as safety issue: No ]
| Estimated Enrollment: | 186 |
| Study Start Date: | December 2009 |
| Estimated Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
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: carboplatin
Given IV
Drug: glutathione
Given IV
Drug: paclitaxel
Given IV
|
|
Placebo Comparator: Arm II
Patients receive placebo IV over 15 minutes, paclitaxel* IV over 3 hours, and carboplatin IV over 30 minutes as in arm I.
|
Drug: carboplatin
Given IV
Drug: paclitaxel
Given IV
Other: placebo
Given IV
|
Detailed Description:
OBJECTIVES:
Primary
- To compare paclitaxel/carboplatin (PC)-induced (PCI) peripheral neuropathy (PN) as measured by EORTC-QLQ-CIPN20 between patients with ovarian cancer and/or primary peritoneal carcinoma treated with glutathione vs placebo.
Secondary
- To compare the incidences of grade 2+ and grade 3+ PCI PN as measured by CTCAE neuropathy scale between the glutathione and placebo arms.
- To compare the time to onset of grade 2+ and grade 3+ PCI PN between the treatment arms as measured by CTCAE neuropathy scale.
- To compare the proportion of patients requiring chemotherapy dose reductions secondary to PCI PN between the treatment arms.
- To compare the proportion of patients stopping PC secondary to peripheral neuropathy between the arms.
- To assess the toxicity profile of glutathione in this situation.
- To evaluate whether glutathione influences the antitumor activity of PC.
- To evaluate patient quality of life as measured by FACT-O and patient daily-symptom questionnaires over time between the treatment arms.
Tertiary (exploratory)
- To explore the association of genetic variations in genes involved in taxane/platinum metabolism with the incidence of grade 2+ PCI PN.
- To bank blood products for future studies.
OUTLINE: Patients are stratified according to baseline neuropathy (none vs grade 1), age (≤ 50 years vs > 50 years), debulked status (no gross residual disease [no clinically apparent residual lesions at the completion of primary surgery] vs optimal [largest residual lesion < 1 cm at primary surgery] vs sub-optimally debulked [residual lesion > 1 cm] or not operated upon), concurrent use of bevacizumab (yes vs no), paclitaxel planned dose (weekly vs every 3 weeks), and diabetes requiring insulin or oral hypoglycemic medications (yes vs no). Patients are randomized to 1 of 2 treatment arms.
Ideally, patients begin receiving glutathione before their first dose of chemotherapy, but must begin glutathione before their second dose of chemotherapy.
- Arm I: 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.
- Arm II: Patients receive placebo IV over 15 minutes, paclitaxel* IV over 3 hours, and carboplatin IV over 30 minutes as in arm I.
NOTE: * Alternatively, patients may receive paclitaxel IV over 1 hour and glutathione/placebo IV over 15 minutes weekly and carboplatin every 21 days for 12 weeks.
Blood samples are collected periodically for pharmacogenomic and other biomarker analyses. Patients complete questionnaires periodically, including quality-of-life assessments.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of stage III/IV ovarian cancer, fallopian tube cancer, and/or primary peritoneal carcinoma
- Scheduled to undergo treatment with paclitaxel at 175 mg/m^2 and carboplatin at area under the curve = 6 every 21 days for 6 courses with or without bevacizumab
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 6 months
- WBC ≥ 3,400/mm^3
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin > 10.0 g/dL
- Creatinine ≤ 1.5 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to complete English language questionnaire(s) alone or with assistance
- Willing to provide blood specimens as required by the study
- No pre-existing history of peripheral neuropathy > grade 1 (NCI CTCAE v4.0) due to any cause (e.g., chemotherapy, diabetes, alcohol, toxin, or heredity)
- No other medical conditions that, in the opinion of the treating physician/allied health professional, would make this study unreasonably hazardous for the patient
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior paclitaxel or carboplatin other than the current treatment regimen
- No other concurrent treatment for the prevention of peripheral neuropathy, including prescription and over-the-counter or herbal therapies
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00979082
Show 334 Study Locations
Show 334 Study LocationsSponsors and Collaborators
North Central Cancer Treatment Group
Investigators
| Study Chair: | Charles L. Loprinzi, MD | North Central Cancer Treatment Group |
More Information
Additional Information:
No publications provided
| Responsible Party: | Jan C. Buckner, North Central Cancer Treatment Group |
| ClinicalTrials.gov Identifier: | NCT00979082 History of Changes |
| Other Study ID Numbers: | CDR0000654097, NCCTG-N08CA |
| Study First Received: | September 16, 2009 |
| Last Updated: | December 13, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Cancer Institute (NCI):
|
neurotoxicity chemotherapeutic agent toxicity pain peripheral neuropathy stage IIIA ovarian epithelial cancer stage IIIB ovarian epithelial cancer stage IIIC ovarian epithelial cancer stage IV ovarian epithelial cancer |
stage IIIA primary peritoneal cavity cancer stage IIIB primary peritoneal cavity cancer stage IIIC primary peritoneal cavity cancer stage IV primary peritoneal cavity cancer stage IIIA fallopian tube cancer stage IIIB fallopian tube cancer stage IIIC fallopian tube cancer stage IV fallopian tube cancer |
Additional relevant MeSH terms:
|
Ovarian Neoplasms Peripheral Nervous System Diseases Peritoneal Neoplasms Fallopian Tube Neoplasms Neurotoxicity Syndromes Demyelinating Diseases Polyneuropathies Nerve Compression Syndromes Neurologic Manifestations Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female |
Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Neuromuscular Diseases Nervous System Diseases Abdominal Neoplasms Digestive System Neoplasms Digestive System Diseases Peritoneal Diseases Fallopian Tube Diseases Poisoning Substance-Related Disorders Signs and Symptoms Carboplatin |
ClinicalTrials.gov processed this record on May 16, 2013