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Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00063999
First received: July 8, 2003
Last updated: October 26, 2016
Last verified: October 2016
  Purpose
This randomized phase III trial compares how well two different combination chemotherapy regimens (doxorubicin hydrochloride, cisplatin, and paclitaxel versus carboplatin and paclitaxel) work in treating patients with endometrial cancer that is stage III-IV or has come back (recurrent). Drugs used in chemotherapy such as doxorubicin hydrochloride, cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which combination chemotherapy regimen is more effective in treating endometrial cancer.

Condition Intervention Phase
Recurrent Uterine Corpus Carcinoma
Stage IIIA Uterine Corpus Cancer
Stage IIIB Uterine Corpus Cancer
Stage IIIC Uterine Corpus Cancer
Stage IVA Uterine Corpus Cancer
Stage IVB Uterine Corpus Cancer
Drug: Carboplatin
Drug: Cisplatin
Drug: Doxorubicin Hydrochloride
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Biological: Pegfilgrastim
Other: Quality-of-Life Assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial of Doxorubicin/Cisplatin/Paclitaxel and G-CSF Versus Carboplatin/Paclitaxel in Patients With Stage III &Amp; IV or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Duration of overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 10 years ] [ Designated as safety issue: No ]
    A log hazard ratio with 90% confidence intervals will be used.


Secondary Outcome Measures:
  • Change in functional well-being assessed using the FACT/GOG Neurotoxicity subscale [ Time Frame: Baseline to up to 26 weeks ] [ Designated as safety issue: No ]
    The difference in time-averaged total score from the subscale will be compared between treatment arms.

  • Change in physical well-being assessed using the Functional Assessment of Cancer Therapy (FACT)-Endometrial subscale [ Time Frame: Baseline to up to 26 weeks ] [ Designated as safety issue: No ]
    The difference in time-averaged total score from the subscale will be compared between treatment arms.

  • Duration of progression-free survival [ Time Frame: From study entry until disease progression, death, or date of last contact, assessed up to 10 years ] [ Designated as safety issue: No ]
    A logrank test or a proportional hazards model will be used to assess the equality of hazard rates between the two regimens.

  • Estrogen and progesterone receptor status (positive or negative) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    This study will investigate the prognostic significance of estrogen and progesterone receptors in patients treated with combination chemotherapy. A proportional hazards model adjusted for performance status and treatment will be used to explore the relationship between receptor status and progression-free survival or survival.

  • Incidence of adverse events [ Time Frame: Up to 3 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    The frequency and severity of AEs was graded by CTC version 2.0, until April 1, 2010 when the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 began being utilized for AE reporting.

  • Number of courses of study therapy administered (for those not completing the prescribed study therapy) [ Time Frame: Up to 21 weeks ] [ Designated as safety issue: No ]
    Will be recorded with the reason for discontinuation.

  • Sites of disease and tumor grade [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The relationship between receptor status and histologic tumor grade will also be explored.


Enrollment: 1331
Study Start Date: August 2003
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given IV
Other Names:
  • 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
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
Biological: Filgrastim
Given SC
Other Names:
  • Filgrastim XM02
  • Filgrastim-sndz
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
  • Zarxio
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Biological: Pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • filgrastim-SD/01
  • HSP-130
  • Neulasta
  • Neulastim
  • Pegfilgrastim Biosimilar HSP-130
  • SD-01
  • SD-01 sustained duration G-CSF
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm II (paclitaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin
Given IV
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
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if the combination of carboplatin and paclitaxel (TC) chemotherapy is therapeutically equivalent to the combination of doxorubicin (doxorubicin hydrochloride), cisplatin and paclitaxel (TAP) chemotherapy with regards to survival.

II. To determine if estrogen/progesterone receptor status provides prognostic information in patients treated with chemotherapy.

III. To assess whether combination TC chemotherapy is superior to combination TAP chemotherapy with regards to toxicity profile, specifically neurotoxicity and infection.

IV. To measure differences in patient-reported neurotoxicity and quality of life (QOL) among the regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients with left ventricular ejection fraction < 50% at randomization who are initially randomized to Arm I are immediately crossed over to Arm II.

ARM I: Patients receive doxorubicin hydrochloride intravenously (IV) over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim subcutaneously (SC) on days 3-12 or pegfilgrastim SC on day 3.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1.

In both arms, treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have primary stage III or stage IV or recurrent endometrial carcinoma whose potential for cure by radiation therapy or surgery alone or in combination is very poor; pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the primary tumor is mandatory; however, the results do not need to be available prior to registration
  • Patients may not have received prior cytotoxic chemotherapy, including chemotherapy used for radiation sensitization; patients may have received prior radiation therapy, hormonal therapy, or therapy with biologic agents, but such therapies must be discontinued prior to entry on this study
  • Patients in whom both radiation and chemotherapy is planned must receive radiation prior to entry on this study; at least four weeks should have elapsed since completion of radiation therapy (RT) involving the whole pelvis or over 50% of the spine
  • Platelets >= 100,000/mcl
  • Granulocytes (absolute neutrophil count [ANC]) >= 1,500/mcl
  • Creatinine =< upper limit of normal (ULN) (Common Toxicity Criteria [CTC] grade 0) or calculated creatinine clearance (Jeliffe Formula) >= 60 ml/min
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limits of normal
  • Bilirubin =< institutional upper limits of normal
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
  • Patients must have met the pre-entry requirements
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Patients with a concomitant malignancy other than non-melanoma skin cancer; with the exception of non-melanoma skin cancer, patients with a prior invasive malignancy who have been disease-free for < 5 years or who received prior chemotherapy for that malignancy
  • Patients in whom pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the tumor is not obtainable
  • Patients for whom radiation therapy is planned during or after study chemotherapy prior to demonstrated progression
  • Patients with concomitant medical illness such as serious uncontrolled infection, uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the treating physician, make the treatments prescribed on this study unreasonably hazardous for the patient
  • Patients with third degree or complete heart block are not eligible unless a pacemaker is in place; patients on medications which alter cardiac conduction, such as digitalis, beta-blockers, or calcium channel blockers, or who have other conduction abnormalities or cardiac dysfunction may be placed on study at the discretion of the investigator
  • Patients with history of myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure or symptoms suspicious for congestive heart failure are not eligible unless a left ventricular ejection fraction in the past 6 months is documented to be 50% or greater; patients who have had a left ventricular ejection fraction (LVEF) (performed for any reason) of less than 50% in the past 6 months are ineligible
  • Patients whose circumstances will not permit study completion or adequate follow-up
  • Patients who are sensitive to E. coli-derived drug preparations
  • Patients with uterine carcinosarcoma or other non-epithelial uterine malignancies
  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: NCT00063999

  Show 542 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Miller NRG Oncology
  More Information

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00063999     History of Changes
Other Study ID Numbers: GOG-0209  NCI-2009-00584  CDR0000305940  GOG-0209  GOG-0209  U10CA180868  U10CA027469 
Study First Received: July 8, 2003
Last Updated: October 26, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Doxorubicin
Carboplatin
Cisplatin
Lenograstim
Succinylcholine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Neuromuscular Depolarizing Agents

ClinicalTrials.gov processed this record on December 02, 2016