Adjuvant Chemotherapy for High Risk Uterine Leiomyosarcoma

• Sponsor: Sarcoma Alliance for Research through Collaboration (Other)
• Overall Status: Completed
• CT.gov ID: NCT00282087
• Collaborator: (none)
• Enrollment: 47
• Locations: 12
• Arm: 1
• Duration (Months): 72
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leiomyosarcoma; Uterine Neoplasm	Drug: gemcitabine, docetaxel, doxorubicin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adjuvant Treatment of High Risk Uterine Leiomyosarcoma With Gemcitabine/Docetaxel Followed by Doxorubicin: A Phase II Trial
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: gemcitabine/docetaxel then doxorubicin Gemcitabine 900 mg/m2 IV over 90 minutes days 1 and 8 Docetaxel 75 mg/m2 IV day 8 (pre-medication dexamethasone 4-8 mg p.o. bid for 3 days, starting 12-24 hours prior to docetaxel). Doxorubicin 60 mg/m2 IVP every 21 days for 4 cycles (recommend use of central venous catheter access).	Drug: gemcitabine, docetaxel, doxorubicin; Cycles = 28 days

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Correlation Between Age and Tumor Response to Treatment (PFS) [2 years]

3. Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS) [2 years]

4. 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

5. Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS) [2 years]

   Mitotic rate is measured in mitoses per 10 high-power fields

6. Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS) [2 years]

7. Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS) [2 years]

8. 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)

9. Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS) [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Cancer Institute/Washington Hospital Center (Medstar)	Washington	District of Columbia	United States	20010
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
3	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30308
4	University of Chicago	Chicago	Illinois	United States	60637
5	St. Vincent Gynecologic Oncology	Indianapolis	Indiana	United States	46260
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	01225
7	Massachusetts General	Boston	Massachusetts	United States	02114
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
10	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
11	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania	United States	19106
12	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Sarcoma Alliance for Research through Collaboration

Investigators

• Principal Investigator: Martee L. Hensley, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• SARC Website

Publications

None provided.

• Responsible Party: Sarcoma Alliance for Research through Collaboration
• ClinicalTrials.gov Identifier: NCT00282087
• Other Study ID Numbers: SARC005; MSKCC05-128
• First Posted: Jan 25, 2006
• Last Update Posted: Dec 1, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Sarcoma Alliance for Research through Collaboration: early stage; high grade; uterine leiomyosarcoma; adjuvant treatment
• Additional relevant MeSH terms: Leiomyosarcoma; Uterine Neoplasms; Gemcitabine; Docetaxel; Doxorubicin

Study Results

Participant Flow

Recruitment Details	This was multi-center study open at 11 major medical centers across the United States.

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description	Gemcitabine 900 mg/m2 on days 1 and 8 intravenously over 90 minutes, followed by Docetaxel 75 mg/m2 on day 8 intravenously over 1 hour.
Period Title: Overall Study
STARTED	47
COMPLETED	46
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Overall Participants	47
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	44 93.6%
>=65 years	3 6.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (16)
Sex: Female, Male (Count of Participants)
Female	47 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	47 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	46
Number (95% Confidence Interval) [percentage of participants]	78 166%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Bayesian Posterior Probability
	Comments
Method of Estimation	Estimation Parameter	Two year PFS
	Estimated Value	78
	Confidence Interval	(2-Sided) 95%; 67 to 91
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Tolerability/Toxicity of This Regimen
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description	Number of major toxicity events
Measure Participants	46
Number [number of major toxicity events]	6

3. Secondary Outcome

Title	Correlation Between Age and Tumor Response to Treatment (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
Median (Full Range) [years]	53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Age correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	-0.00269
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
Postmenopausal	43 91.5%
Premenopausal	4 8.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Menopausal status at diagnosis correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS)
Description	AJCC Stage I: No serosal involvement AJCC Stage II: No serosal involement AJCC Stage III: Serosal only
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
AJCC Stage I	0 0%
AJCC Stage II	6 12.8%
AJCC Stage III	41 87.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Uterine serosal involvement correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.101
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS)
Description	Mitotic rate is measured in mitoses per 10 high-power fields
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
Median (Full Range) [mitoses per 10 high-power fields]	18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Mitotic rate correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	-0.00676
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Only 38 of the 47 patients were evaluable

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	38
Positive Status	24 51.1%
Negative Status	14 29.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Estrogen receptor (ER) status correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	-0.708
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Only 38 of the 47 patients were evaluable

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	38
Positive Status	19 40.4%
Negative Status	19 40.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Progesterone receptor (PR) status correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	-0.906
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
FIFO Stage I	38 80.9%
FIGO Stage II	7 14.9%
FIGO Stage III	2 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	1988 FIGO Stage correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.207
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
Measure Participants	47
ER or PR Positive	33 70.2%
ER and PR Negative	14 29.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Comments	Estrogen receptor (ER) or progesterone receptor (PR) positive correlation with progression-free survival for patients on study treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	-0.564
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
Arm/Group Description
All Cause Mortality
	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Affected / at Risk (%)	# Events
Total	9/47 (19.1%)
Blood and lymphatic system disorders
Neutropenia	2/47 (4.3%)	2
Blood clot	1/47 (2.1%)	1
Renal insufficiency	1/47 (2.1%)	1
Cardiac disorders
Chest Pain	2/47 (4.3%)	2
Gastrointestinal disorders
Perforation of bowel	1/47 (2.1%)	1
Colostomy Reversal	1/47 (2.1%)	1
Diarrhea	1/47 (2.1%)	1
General disorders
Fever	1/47 (2.1%)	1
Infections and infestations
Infection	1/47 (2.1%)	1
Injury, poisoning and procedural complications
Hernia	1/47 (2.1%)	1
Investigations
Neutrophils	2/47 (4.3%)	2
Bilirubin	1/47 (2.1%)	1
Platelets	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Throat Pain	1/47 (2.1%)	1
Skin and subcutaneous tissue disorders
Cellulitis	1/47 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Women Treated With Adjuvant Regimen for High Risk Uterine LMS
	Affected / at Risk (%)	# Events
Total	14/47 (29.8%)
Endocrine disorders
myelosuppression	14/47 (29.8%)
Immune system disorders
Hypersensitivity	10/47 (21.3%)
Nervous system disorders
neuropathy	3/47 (6.4%)
Skin and subcutaneous tissue disorders
Edema	2/47 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.