NCT01533207|TerminatedPhase 3Results

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

Gynecologic Oncology Group ClinicalTrials.gov

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6 other identifiers

GOG-0277NCI-2012-00249CDR0000724874IRCI 001U10CA180868U10CA027469

Study Type

interventional

Target

Locations

8 countries

Sites

623

Timeline

RegisteredFeb 2012

StartedJun 2012

CompletionFeb 2019

Brief 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.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

Completed

Started Jun 2012

Longer than P75 for phase_3

Geographic Reach

8 countries

623 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.7 years study duration

First Submitted

Initial submission to the registry

February 11, 2012

Completed

4 days until next milestone

First Posted

Study publicly available on registry

February 15, 2012

Completed

4 months until next milestone

Study Start

First participant enrolled

June 4, 2012

Completed

6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2018

Completed

7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 9, 2019

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

April 6, 2020

Completed

Last Updated

April 28, 2020

Status Verified

April 1, 2020

Enrollment Period

6.1 years

First QC Date

February 11, 2012

Results QC Date

February 27, 2019

Last Update Submit

April 20, 2020

Conditions

Stage I Uterine Sarcoma AJCC v7 Uterine Corpus Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

Number of Participants Who Experienced Death
The duration of time from study entry to time of death or the date of last contact.
Follow-up every 4 months for 3 years, then every 6 months for 2 years.

Secondary Outcomes (2)

Incidence of Grade 3 or Higher Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Approximately 4 years
Number of Participants With Recurrence
Follow-up every 4 months for 3 years, then every 6 months for 2 years.

Other Outcomes (1)

Univariate and Multi-variable Prognostic Significance of Baseline Clinical, Pathologic, or Demographic Factors
Up to 5 years

Study Arms (2)

Arm I (chemotherapy)

EXPERIMENTAL

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.

Drug: DocetaxelDrug: Doxorubicin HydrochlorideBiological: FilgrastimDrug: Gemcitabine HydrochlorideBiological: Pegfilgrastim

Arm II (no treatment)

OTHER

Patients undergo clinical observation.

Other: Clinical Observation

Interventions

Clinical ObservationOTHER

Patients followed clinically

Also known as: observation

Arm II (no treatment)

DocetaxelDRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Arm I (chemotherapy)

Doxorubicin HydrochlorideDRUG

Given IV

Also known as: 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

Arm I (chemotherapy)

FilgrastimBIOLOGICAL

Given subcutaneously (SC)

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Arm I (chemotherapy)

Gemcitabine HydrochlorideDRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Arm I (chemotherapy)

PegfilgrastimBIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Pegfilgrastim Biosimilar HSP-130, SD-01, SD-01 sustained duration G-CSF

Arm I (chemotherapy)

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patients with high-risk uterine leiomyosarcoma (LMS), 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 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 bilateral salpingo-oophorectomy (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/liter \[L\])
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
+5 more criteria

You may not qualify if:

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 also 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 prior 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; documentation of concurrent medications is required
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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Gynecologic Oncology Grouplead
National Cancer Institute (NCI)collaborator

Study Sites (623)

Tennessee Valley Gynecologic Oncology

Huntsville, Alabama, 35805, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC