Leiomyosarcoma, Uterine Neoplasm
Conditions
Keywords
early stage, high grade, uterine leiomyosarcoma, adjuvant treatment
Brief summary
The purpose of this trial is to study the benefits of giving chemotherapy to women after they have had surgical resection of their primary disease and have no evidence of disease remaining(known as adjuvant therapy). The major objective of this study is to determine the progression free survival. The goal is to prevent relapse or recurrence of their uterine leiomyosarcoma.
Detailed description
Patients with a diagnosis of early-stage uterine leiomyosarcoma have a 70% chance of relapse or recurrence of their disease. Patients enrolled in this trial will receive 4 cycles of gemcitabine and docetaxel followed by 4 cycles of adriamycin. Following completion of chemotherapy, they will be have repeat imaging at regular intervals to monitor for disease recurrence along with periodic clinical evaluations.
Interventions
DRUGgemcitabine, docetaxel, doxorubicin
Cycles = 28 days
Sponsors
Sarcoma Alliance for Research through Collaboration
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age * high risk uterine LMS, FIGO stage I or II * pathology review of LMS high grade and /or mitotic rate greater than or equal to 5 mitoses/10 hpf * no longer than 12 weeks from surgical resection of cancer * no evidence of residual disease * ECOG 0 or 1 * ANC ≥ 1,500, hemoglobin ≥ 8.0, platelets ≥100,000 * creatinine ≤ 1.5 x institutional upper limits of normal * adequate liver function * neuropathy (sensory and motor) ≤ CTC grade 1 * negative pregnancy test * signed consent
Exclusion criteria
* patients with other invasive malignancies * prior therapy with gemcitabine or docetaxel or doxorubicin * hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 * women who are breast feeding * cardiac ejection fraction \<50% * prior pelvic irradiation * treatment with hormone replacement or anti-hormonal agents or other cytotoxic agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS | Every 3 months up to two years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability/Toxicity of This Regimen | Every 28 days during dosing and then every 3 months thereafter until patient comes off study | Unacceptable toxicity is defined as grade 3 or 4 non-hematologic toxicity events that are considered to be treatment-related, excluding alopecia and fatigue. |
| Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS) | 2 years | — |
| Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS) | 2 years | AJCC Stage I: No serosal involvement AJCC Stage II: No serosal involement AJCC Stage III: Serosal only |
| Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS) | 2 years | Mitotic rate is measured in mitoses per 10 high-power fields |
| Correlation Between Age and Tumor Response to Treatment (PFS) | 2 years | — |
| Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS) | 2 years | — |
| Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS) | 2 years | Stage I: confined to the uterine corpus Stage II: confined to corpus and cervix Stage IIIA: serosa involvement only (disease could involve the uterine serosa, but patients must have had no other evidence of local spread) |
| Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS) | 2 years | — |
| Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS) | 2 years | — |
Countries
United States
Participant flow
Recruitment details
This was multi-center study open at 11 major medical centers across the United States.
Participants by arm
| Arm | Count |
|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Women Treated With Adjuvant Regimen for High Risk Uterine LMS |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 16 |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 47 |
| serious Total, serious adverse events | 9 / 47 |
Outcome results
Primary
Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS
Time frame: Every 3 months up to two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS | 78 percentage of participants |
Comparison: The primary endpoint is progression-free survival time, with progression defined as a patient having evidence of recurrent LMS on follow-up evaluation and CT scan. Futility monitoring will be based on the accumulating right-censored PFS time data. The monitoring rules will be based on a Bayesian model.p-value: 0.1595% CI: [67, 91]Bayesian Posterior Probability
Secondary
Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS)
Stage I: confined to the uterine corpus Stage II: confined to corpus and cervix Stage IIIA: serosa involvement only (disease could involve the uterine serosa, but patients must have had no other evidence of local spread)
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS) | FIFO Stage I | 38 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS) | FIGO Stage II | 7 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS) | FIGO Stage III | 2 participants |
Comparison: 1988 FIGO Stage correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Age and Tumor Response to Treatment (PFS)
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Age and Tumor Response to Treatment (PFS) | 53 years |
Comparison: Age correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS)
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS) | ER or PR Positive | 33 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS) | ER and PR Negative | 14 participants |
Comparison: Estrogen receptor (ER) or progesterone receptor (PR) positive correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS)
Time frame: 2 years
Population: Only 38 of the 47 patients were evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS) | Positive Status | 24 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS) | Negative Status | 14 participants |
Comparison: Estrogen receptor (ER) status correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS)
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS) | Postmenopausal | 43 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS) | Premenopausal | 4 participants |
Comparison: Menopausal status at diagnosis correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS)
Mitotic rate is measured in mitoses per 10 high-power fields
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS) | 18 mitoses per 10 high-power fields |
Comparison: Mitotic rate correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS)
Time frame: 2 years
Population: Only 38 of the 47 patients were evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS) | Positive Status | 19 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS) | Negative Status | 19 participants |
Comparison: Progesterone receptor (PR) status correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS)
AJCC Stage I: No serosal involvement AJCC Stage II: No serosal involement AJCC Stage III: Serosal only
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS) | AJCC Stage I | 0 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS) | AJCC Stage II | 6 participants |
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS) | AJCC Stage III | 41 participants |
Comparison: Uterine serosal involvement correlation with progression-free survival for patients on study treatment.Cox Proportional Hazards
Secondary
Tolerability/Toxicity of This Regimen
Unacceptable toxicity is defined as grade 3 or 4 non-hematologic toxicity events that are considered to be treatment-related, excluding alopecia and fatigue.
Time frame: Every 28 days during dosing and then every 3 months thereafter until patient comes off study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | Tolerability/Toxicity of This Regimen | 6 number of major toxicity events |