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Gemcitabine Hydrochloride and Docetaxel Followed by Doxorubicin Hydrochloride or Observation in Treating Patients With High-Risk Uterine Leiomyosarcoma Previously Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Gynecologic Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01533207
First received: February 11, 2012
Last updated: March 25, 2014
Last verified: March 2014

February 11, 2012
March 25, 2014
June 2012
February 2018   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: From study entry to time of death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
The logrank test will be used to test the null hypothesis of independence between survival and randomized treatment. Kaplan-Meier estimates will be used to graph survival distribution curves for each treatment arm. The death hazard ratio (experimental to control) will be estimated using a Cox Proportional Hazards model and a 95% Wald confidence interval will be reported.
Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01533207 on ClinicalTrials.gov Archive Site
  • Recurrence-free survival [ Time Frame: From study entry to time of recurrence or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    The recurrence or death hazard ratio (experimental to control) will be estimated using Cox's proportional hazards model and a 95% Wald confidence interval will be reported. The logrank test will be used to test the null hypothesis of independence between recurrence-free survival and randomized treatment.
  • Frequency and severity of adverse events as assessed by NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Recurrence-free survival [ Designated as safety issue: No ]
  • Frequency and severity of adverse events [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Gemcitabine Hydrochloride and Docetaxel Followed by Doxorubicin Hydrochloride or Observation in Treating Patients With High-Risk Uterine Leiomyosarcoma Previously Removed by Surgery
A Phase III Randomized Trial of Gemcitabine (NSC# 613327) Plus Docetaxel (NSC# 628503) Followed by Doxorubicin (NSC# 123127) Versus Observation for Uterus-Limited, High-Grade Uterine Leiomyosarcoma

This randomized phase III trial studies how well gemcitabine hydrochloride and docetaxel followed by doxorubicin hydrochloride work compared to observation in treating patients with high-risk uterine leiomyosarcoma previously removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, docetaxel, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination therapy after surgery is an effective treatment for uterine leiomyosarcoma.

PRIMARY OBJECTIVES:

I. To determine whether overall survival of patients with uterus-limited high-grade leiomyosarcoma is superior among patients assigned to treatment with adjuvant gemcitabine hydrochloride plus docetaxel followed by doxorubicin hydrochloride compared to patients assigned to observation.

SECONDARY OBJECTIVES:

I. To determine whether treatment with adjuvant gemcitabine plus docetaxel followed by doxorubicin improves recurrence-free survival of patients with uterus-limited high-grade leiomyosarcoma compared to observation.

II. To explore the impact of potential predictors of recurrence or death such as patient age, institution-reported tumor size, cervix involvement (yes or no), and mitotic rate. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to country of treating site. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive adjuvant gemcitabine hydrochloride IV over 70-90 minutes on days 1 and 8 and docetaxel IV over 30-60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo computed tomography (CT) and/or magnetic resonance imaging (MRI). Patients with no evidence of disease receive doxorubicin hydrochloride IV every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim SC on days 2-8 or pegfilgrastim SC on day 2 or 3.

Arm II: Patients undergo clinical observation.

Patients may undergo tumor tissue sample collection at baseline for future correlative studies.

After completion of study treatment, patients in both arms are followed up every 4 months for 3 years and then every 6 months for 2 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stage I Uterine Sarcoma
  • Uterine Leiomyosarcoma
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Drug: docetaxel
    Given IV
    Other Names:
    • RP 56976
    • Taxotere
    • TXT
  • Biological: filgrastim
    Given subcutaneously (SC)
    Other Names:
    • G-CSF
    • Neupogen
  • Biological: pegfilgrastim
    Given SC
    Other Names:
    • Filgrastim SD-01
    • GCSF-SD01
    • Neulasta
    • SD-01 sustained duration G-CSF
  • Other: clinical observation
    Patients followed clinically
    Other Name: observation
  • Experimental: Arm I (chemotherapy)
    Patients receive adjuvant gemcitabine hydrochloride IV over 70-90 minutes on days 1 and 8 and docetaxel IV over 30-60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo CT and/or MRI. Patients with no evidence of disease receive doxorubicin hydrochloride IV every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim SC on days 2-8 or pegfilgrastim SC on day 2 or 3.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: gemcitabine hydrochloride
    • Drug: docetaxel
    • Biological: filgrastim
    • Biological: pegfilgrastim
  • Arm II (no treatment)
    Patients undergo clinical observation.
    Intervention: Other: clinical observation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
216
Not Provided
February 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with high-risk uterine leiomyosarcoma (LMS), International Federation of Gynecology and Obstetrics (FIGO) stage I (confined to corpus +/- cervix); patients with known uterine serosa involvement are not eligible; patients should have had, at least, a complete hysterectomy (including removal of the cervix); bilateral salpingo-oophorectomy (BSO) is not required

    • Institutional pathology review calls the uterine leiomyosarcoma "high grade"
    • Additionally, if the pathology report indicates a mitotic rate, the mitotic rate should be greater than or equal to 5 mitoses/10 high-power field
    • All patients must be no longer than 12 weeks (3 months) from surgical resection of cancer at the time of enrollment on study; if a patient requires a second operation to complete her surgery, i.e., trachelectomy to remove the cervix and/or BSO, the 12 weeks may be counted from the time of the second operation
    • Patients who had a "morcellation" hysterectomy procedure that involved morcellation within the peritoneal cavity are eligible IF a second operation is performed and biopsies from the second procedure show no evidence of leiomyosarcoma
  • All patients must have no evidence of persistent or metastatic disease as documented by a post-resection computed tomography (CT) of the chest/abdomen/pelvis or by CT chest + magnetic resonance imaging (MRI) abdomen/pelvis; the post-resection imaging studies should be performed within 4 weeks of registration on study
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL (ANC >= 1.5 x 10^9/L)
  • Platelets greater than or equal to 100,000/mcL (platelets >= 100 x 10^9/L)
  • Hemoglobin greater than 8.0 g/dL (= 80 g/L or 4.9 mmol/L)
  • Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)
  • Bilirubin* within normal range
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])* and serum glutamic pyruvate transaminase(SGPT) (alanine aminotransferase [ALT])* less than or equal to 2.5 times ULN
  • Alkaline phosphatase* less than or equal to 2.5 x ULN
  • * Patients with a history of Gilbert's syndrome may be eligible provided total bilirubin is less than or equal to 1.5 x ULN and the AST, ALT, and alkaline phosphatase meet the criteria detailed
  • Neuropathy (sensory and motor) less than or equal to Common Terminology Criteria for Adverse Events(CTCAE) grade 1
  • Patients with Gynecologic Oncology Group (GOG) performance status (PS) of 0 or 1 OR Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 OR Karnofsky PS >= 80%
  • Patients must have signed an approved informed consent
  • Patients participating through U.S. sites must sign an approved and authorization permitting release of personal health information
  • Patients should be free of active infection requiring antibiotics (with the exception of an uncomplicated urinary tract infection [UTI])

Exclusion Criteria:

  • Patients who have had prior therapy with docetaxel, gemcitabine hydrochloride, or doxorubicin hydrochloride at any time in their history
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are ineligible if there is any evidence of other malignancy being present within the last five years
  • Patients are ineligible if their previous cancer treatment contraindicates this protocol therapy
  • Patients with a history of severe hypersensitivity reaction to Taxotere (docetaxel) or other drugs formulated with polysorbate 80
  • Patients with GOG performance status of 2, 3 or 4; or ECOG performance status of 2, 3 or 4
  • Patients who are breast-feeding
  • Patients with a known history of congestive heart failure or cardiac ejection fraction < 50% (or less than institutional normal limits); echocardiogram (ECHO) or multigated acquisition scan (MUGA) is not required prior to enrollment; for patients assigned to the chemotherapy arm, an ECHO or MUGA should be done within 6 months of day 1 of gemcitabine-docetaxel treatment

    • Patients who enroll on study and are randomized to Regimen I (chemotherapy ) and then are found on baseline ECHO or MUGA to have cardiac ejection fraction < 50% or below institutional normal will remain ON study; such patients will receive gemcitabine + docetaxel for 4 cycles but will NOT receive any doxorubicin treatment; they will continue treatment follow-up as outlined for all patients assigned to Regimen I
  • Patients with a history of whole pelvic radiation
  • Concurrent treatment with hormone replacement therapy is permitted at the discretion of the treating physician; patients who have been taking hormonal/hormone-blocking agents for breast cancer or breast cancer prevention or other indication are eligible; use of anti-hormonal agents (tamoxifen, medroxyprogesterone, aromatase inhibitors) is permitted at the discretion of the treating physician
  • Patients with recurrent uterine LMS
  • Patients who are known to be human immunodeficiency virus (HIV) positive are not eligible
  • Patients with gross residual or metastatic tumor findings following complete surgical treatment for uterine LMS
Female
18 Years and older
No
United States
 
NCT01533207
GOG-0277, NCI-2012-00249, CDR0000724874, IRCI 001, GOG-0277, GOG-0277, U10CA027469
Not Provided
Gynecologic Oncology Group
Gynecologic Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Martee Hensley Gynecologic Oncology Group
Gynecologic Oncology Group
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP