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

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIITreatmentActive18 and overGOG-0277
NCI-2012-00249, CDR0000724874, IRCI 001, NCT01533207

Trial Description

Summary

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, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination therapy after surgery is an effective treatment for uterine leiomyosarcoma.

Further Study Information

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: 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.

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.

Eligibility Criteria

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 glutamate 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 who have met the pre-entry requirements specified

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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NRG Oncology

  • National Cancer Institute
Martee Leigh Hensley, Principal Investigator

Trial Sites

U.S.A.

Colorado
Denver

Colorado Cancer Research Program NCORP

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator

Iowa
Des Moines

Iowa-Wide Oncology Research Coalition NCORP

Robert J. Behrens
Ph: 515-282-2921

Robert J. Behrens
Principal Investigator

Montana
Billings

Montana Cancer Consortium NCORP

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Wisconsin
Johnson Creek

UW Cancer Center Johnson Creek

David M. Kushner
Ph: 877-405-6866

David M. Kushner
Principal Investigator

Venezuela

Caracas

Hospital Universitario

Antonio Casado Herraez
Ph: 888-823-5923
Email: ctsucontact@westat.com

Antonio Casado Herraez
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01533207

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.