Back to resultsComparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix
Primary Purpose
Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Gemcitabine Hydrochloride
Paclitaxel
Quality-of-Life Assessment
Topotecan Hydrochloride
Vinorelbine Tartrate
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Adenocarcinoma
Eligibility Criteria
Inclusion Criteria: Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix Stage IVB, recurrent, or persistent disease Not amenable to curative surgery and/or radiotherapy At least 1 unidimensionally measurable lesion At least 20 mm by palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by spiral CT scan Biopsy confirmation required if lesion is less than 30 mm Target lesion must be outside of a previously irradiated field No craniospinal metastases Performance status - GOG 0-1 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times normal Alkaline phosphatase no greater than 3 times normal AST no greater than 3 times normal Creatinine ≤ 1.2 mg/dL Creatinine > 1.2 mg/dL but < 1.5 mg/dL AND creatinine clearance ≥ 50 mL/min No bilateral hydronephrosis not alleviated by ureteral stents or percutaneous drainage Not pregnant or nursing Fertile patients must use effective contraception No prior or concurrent malignancy within the past 5 years except nonmelanoma skin cancer No prior malignancy whose treatment contraindicates the current study therapy No concurrent clinically significant infection No concurrent cytokines At least 6 weeks since prior chemoradiotherapy and recovered No prior chemotherapy (except when concurrently administered with radiotherapy) At least 3 weeks since prior radiotherapy and recovered Recovered from prior surgery
Sites / Locations
- Gynecologic Oncology Group
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm I (paclitaxel, cisplatin)
Arm II (vinorelbine, cisplatin)
Arm III (gemcitabine, cisplatin)
Arm IV (topotecan, cisplatin)
Arm Description
Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.
Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.
Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.
Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.
Outcomes
Primary Outcome Measures
Duration of Overall Survival (OS)
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Secondary Outcome Measures
Frequency of Response Using RECIST Version 1.0
RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above.
Duration of Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Patient-reported Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT)-Cervical Trial Outcome of Index (FACT-Cx TOI)
The FACT-Cx TOI is a scale for assessing general QOL of cervical cancer patients.consisting of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Cervical Cancer subscale (15 items). Each item in the FACT-Cx TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The score is calculated as the sum of the subscale scores if more than 80% of the FACT-Cx TOI items provide valid answers and all of the component subscales have valid scores. The score ranges 0-116 with a large score suggesting better QOL.
Pain, Assessed by Brief Pain Inventory
Single item from the Brief Pain Inventory (BPI) assessing "worst pain" in the past 24 hours, on a 0-10 scale with a higher score indicating more pain than a low score.
Patient Reported Neurotoxicity Symptoms as Measured With the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity Subscale (Short Version) (FACT/GOG-Ntx Subscale).
The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity.
Full Information
NCT ID
NCT00064077
First Posted
July 8, 2003
Last Updated
September 18, 2018
Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00064077
Brief Title
Comparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix
Official Title
A Randomized Phase III Trial Of Paclitaxel Plus Cisplatin Versus Vinorelbine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Versus Topotecan Plus Cisplatin In Stage IVB, Recurrent Or Persistent Carcinoma of the Cervix
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
This randomized phase III trial is studying four combination chemotherapy regimens using cisplatin to compare how well they work in treating women with stage IVB, recurrent, or persistent cancer of the cervix. Drugs used in chemotherapy such as cisplatin, paclitaxel, vinorelbine, gemcitabine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen containing cisplatin is most effective in treating cervical cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. Compare the survival and response of patients with stage IVB, recurrent, or persistent carcinoma of the cervix when treated with paclitaxel and cisplatin vs vinorelbine and cisplatin vs gemcitabine and cisplatin vs topotecan and cisplatin.
II. Compare the toxic effects of these regimens in these patients. III. Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.
ARM II: Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.
ARM III: Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.
ARM IV: Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.
In all arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, before courses 2 and 5, and at 9 months after study entry.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Carcinoma, Stage IVB Cervical Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
513 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (paclitaxel, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.
Arm Title
Arm II (vinorelbine, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.
Arm Title
Arm III (gemcitabine, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.
Arm Title
Arm IV (topotecan, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Topotecan Hydrochloride
Other Intervention Name(s)
Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vinorelbine Tartrate
Other Intervention Name(s)
Biovelbin, Eunades, KW-2307, Navelbine, Navelbine Ditartrate, NVB, Vinorelbine Ditartrate
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Duration of Overall Survival (OS)
Description
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame
Baseline, every other cycle during treatment, then every 3 months for 2 years, the every 6 months for 3 years (up to 5 years)
Secondary Outcome Measure Information:
Title
Frequency of Response Using RECIST Version 1.0
Description
RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above.
Time Frame
Baseline, every other cycle during treatment, then every 3 months for 2 years, the every 6 months for 3 years (up to 5 years)
Title
Duration of Progression-free Survival (PFS)
Description
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Time Frame
Baseline, every other cycle during treatment, then every 3 months for 2 years, the every 6 months for 3 years (up to 5 years)
Title
Patient-reported Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT)-Cervical Trial Outcome of Index (FACT-Cx TOI)
Description
The FACT-Cx TOI is a scale for assessing general QOL of cervical cancer patients.consisting of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Cervical Cancer subscale (15 items). Each item in the FACT-Cx TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The score is calculated as the sum of the subscale scores if more than 80% of the FACT-Cx TOI items provide valid answers and all of the component subscales have valid scores. The score ranges 0-116 with a large score suggesting better QOL.
Time Frame
Baseline (pre-cycle 1), Pre-cycle 2, Pre-cycle 5, 9 months post cycle 1
Title
Pain, Assessed by Brief Pain Inventory
Description
Single item from the Brief Pain Inventory (BPI) assessing "worst pain" in the past 24 hours, on a 0-10 scale with a higher score indicating more pain than a low score.
Time Frame
Baseline (pre-cycle 1), Pre-cycle 2, Pre-cycle 5, 9 months post cycle 1
Title
Patient Reported Neurotoxicity Symptoms as Measured With the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity Subscale (Short Version) (FACT/GOG-Ntx Subscale).
Description
The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity.
Time Frame
Baseline (pre-cycle 1), Pre-cycle 2, Pre-cycle 5, 9 months post cycle 1
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
Stage IVB, recurrent, or persistent disease
Not amenable to curative surgery and/or radiotherapy
At least 1 unidimensionally measurable lesion
At least 20 mm by palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by spiral CT scan
Biopsy confirmation required if lesion is less than 30 mm
Target lesion must be outside of a previously irradiated field
No craniospinal metastases
Performance status - GOG 0-1
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 times normal
Alkaline phosphatase no greater than 3 times normal
AST no greater than 3 times normal
Creatinine ≤ 1.2 mg/dL
Creatinine > 1.2 mg/dL but < 1.5 mg/dL AND creatinine clearance ≥ 50 mL/min
No bilateral hydronephrosis not alleviated by ureteral stents or percutaneous drainage
Not pregnant or nursing
Fertile patients must use effective contraception
No prior or concurrent malignancy within the past 5 years except nonmelanoma skin cancer
No prior malignancy whose treatment contraindicates the current study therapy
No concurrent clinically significant infection
No concurrent cytokines
At least 6 weeks since prior chemoradiotherapy and recovered
No prior chemotherapy (except when concurrently administered with radiotherapy)
At least 3 weeks since prior radiotherapy and recovered
Recovered from prior surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bradley Monk
Organizational Affiliation
Gynecologic Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gynecologic Oncology Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Comparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix
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