Evaluation of Side Effects and Relative Activity of Two Chemotherapy Regimens in the Treatment Soft Tissue Sarcoma

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00189137
• Collaborator: (none)
• Enrollment: 84
• Location: 1
• Arms: 2
• Duration (Months): 134
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to explore how a sarcoma is affected by and the side effects of a newer combination of chemotherapy drugs(gemcitabine and docetaxel)as compared to a standard combination of chemotherapy drugs, ifosfamide and doxorubicin.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Soft Tissue	Drug: ifosfamide and doxorubicin vs gemcitabine and docetaxel	Phase 2

Detailed Description

The purpose of this study is to explore the relative activity and toxicity of a newer combination of chemotherapy drugs, gemcitabine and docetaxel, as compared to a standard combination of chemotherapy drugs, ifosfamide and doxorubicin.

Ifosfamide and Doxorubicin, given in combination, are recognized as a standard of care for some types of sarcoma. Both gemcitabine and docetaxel are approved by the US Food and Drug Administration (FDA) for the treatment of some cancers (cancers of the pancreas, lung) because patients with those cancers treated with either gemcitabine or docetaxel experienced shrinkage of their tumor or improvement in their symptoms. However, neither gemcitabine or docetaxel is approved for sarcoma, but the combination of gemcitabine and docetaxel is a standard treatment for advanced sarcoma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Evaluation of Ifosfamide Plus Doxorubicin & Filgrastim Versus Gemcitabine Plus Docetaxel & Filgrastim in the Treatment of Localized Poor Prognosis Soft Tissue Sarcoma
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: doxorubicin and ifosfamide	Drug: ifosfamide and doxorubicin vs gemcitabine and docetaxel; Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.
Experimental: gemcitabine and docetaxel	Drug: ifosfamide and doxorubicin vs gemcitabine and docetaxel; Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Hospitalized in Each Arm. [12 weeks]

   To contrast the proportion of treated patients hospitalized subsequent to treatment with gemcitabine and docetaxel as compared to doxorubicin and ifosfamide as neoadjuvant or adjuvant therapy of poor prognosis soft tissue sarcoma.

Secondary Outcome Measures

1. The Percentage of Patients Alive Without Disease at 2 Years [2 years]

   Disease-free survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• no evidence of metastasis

• soft tissue sarcoma

• intermediate or high histologic grade

• greater than 5 cm

• Zubrod performance status 1 or better

• age 10 or older

Exclusion Criteria:

• clear cell, alveolar soft part, Ewing's rhabdosarcoma, undifferentiated small cell or Kaposi's

• prior chemotherapy

• nephrectomy

• active unstable angina pectoris

• concurrent therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Scott Schuetze, MD, PhD, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00189137
• Other Study ID Numbers: UMCC 2004.010; HUM 44800
• First Posted: Sep 16, 2005
• Last Update Posted: Dec 7, 2015
• Last Verified: Nov 1, 2015

• Additional relevant MeSH terms: Sarcoma; Gemcitabine; Docetaxel; Doxorubicin; Ifosfamide

Study Results

Participant Flow

Recruitment Details	84 patients were enrolled and randomized at the University of Michigan, however 4 patients withdrew consent prior to treatment. 80 patients began study treatment.

Arm/Group Title	Doxorubicin and Ifosfamide	Gemcitabine and Docetaxel
Arm/Group Description	Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.	Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.
Period Title: Overall Study
STARTED	37	43
COMPLETED	37	43
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Doxorubicin and Ifosfamide	Gemcitabine and Docetaxel	Total
Arm/Group Description	Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.	Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.	Total of all reporting groups
Overall Participants	37	43	80
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55	57	56
Sex: Female, Male (Count of Participants)
Female	15 40.5%	12 27.9%	27 33.8%
Male	22 59.5%	31 72.1%	53 66.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Hospitalized in Each Arm.
Description	To contrast the proportion of treated patients hospitalized subsequent to treatment with gemcitabine and docetaxel as compared to doxorubicin and ifosfamide as neoadjuvant or adjuvant therapy of poor prognosis soft tissue sarcoma.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxorubicin and Ifosfamide	Gemcitabine and Docetaxel
Arm/Group Description	Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.	Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.
Measure Participants	37	43
Number [percentage of patients hospitalized]	35	26

2. Secondary Outcome

Title	The Percentage of Patients Alive Without Disease at 2 Years
Description	Disease-free survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxorubicin and Ifosfamide	Gemcitabine and Docetaxel
Arm/Group Description	Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.	Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.
Measure Participants	37	43
Number [percentage of patients]	57	74

Adverse Events

Arm/Group Title	Doxorubicin and Ifosfamide		Gemcitabine and Docetaxel
Arm/Group Description	Arm 1 will consist of the two drug combination of doxorubicin and ifosfamide (with mesna) Treatment will be delivered over 3 days at 21 day intervals. Patients will receive filgrastim days 4-10 or peg-filgrastim on day 4 as a myeloid growth factor. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.		Arm 2 will consist of the two drug combination of gemcitabine (day 1, 8) and docetaxel (day 8) repeated at 21 day intervals. Patients will receive filgrastim as a myeloid growth factor days 9-15 or peg-filgrastim on day 4. All patients will receive 4 cycles of chemotherapy unless there is unacceptable toxicity or disease progression that may adversely impact the surgical plan for complete resection.
All Cause Mortality
	Doxorubicin and Ifosfamide		Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Doxorubicin and Ifosfamide		Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/37 (32.4%)		12/43 (27.9%)
Blood and lymphatic system disorders
Febrile neutropenia	6/37 (16.2%)		0/43 (0%)
Hemoglobin	1/37 (2.7%)		0/43 (0%)
Neutrophils/granulocytes (ANC/AGC)	2/37 (5.4%)		0/43 (0%)
Cardiac disorders
Cardiac ischemia/infarction	1/37 (2.7%)		0/43 (0%)
Cardiac troponin I (cTnI)	1/37 (2.7%)		0/43 (0%)
Gastrointestinal disorders
Dysphagia (difficulty swallowing)	1/37 (2.7%)		0/43 (0%)
Esophagitis	1/37 (2.7%)		0/43 (0%)
Colitis	0/37 (0%)		1/43 (2.3%)
Diarrhea	0/37 (0%)		1/43 (2.3%)
Nausea	0/37 (0%)		1/43 (2.3%)
General disorders
Edema: limb	0/37 (0%)		1/43 (2.3%)
Fever	0/37 (0%)		2/43 (4.7%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils	1/37 (2.7%)		0/43 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils	0/37 (0%)		4/43 (9.3%)
Metabolism and nutrition disorders
Dehydration	1/37 (2.7%)		0/43 (0%)
Phosphate, serum-low (hypophosphatemia)	1/37 (2.7%)		0/43 (0%)
Potassium, serum-low (hypokalemia)	1/37 (2.7%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
Ataxia (incoordination)	1/37 (2.7%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/37 (2.7%)		0/43 (0%)
Vascular disorders
Hemorrhage, pulmonary/upper respiratory	0/37 (0%)		1/43 (2.3%)
Thrombosis/thrombus/embolism	0/37 (0%)		1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Doxorubicin and Ifosfamide		Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/37 (81.1%)		33/43 (76.7%)
Blood and lymphatic system disorders
Febrile neutropenia	6/37 (16.2%)		0/43 (0%)
Hemoglobin	9/37 (24.3%)		4/43 (9.3%)
Leukocytes (total WBC)	25/37 (67.6%)		7/43 (16.3%)
Lymphopenia	8/37 (21.6%)		5/43 (11.6%)
Neutrophils/granulocytes (ANC/AGC)	23/37 (62.2%)		7/43 (16.3%)
Platelets	12/37 (32.4%)		6/43 (14%)
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	0/37 (0%)		1/43 (2.3%)
Cardiac disorders
Cardiac ischemia/infarction	1/37 (2.7%)		0/43 (0%)
Cardiac troponin I (cTnI)	1/37 (2.7%)		0/43 (0%)
Gastrointestinal disorders
Dysphagia (difficulty swallowing)	1/37 (2.7%)		0/43 (0%)
Esophagitis	2/37 (5.4%)		0/43 (0%)
Colitis	0/37 (0%)		1/43 (2.3%)
Constipation	0/37 (0%)		1/43 (2.3%)
Diarrhea	0/37 (0%)		1/43 (2.3%)
Nausea	0/37 (0%)		1/43 (2.3%)
Vomiting	0/37 (0%)		1/43 (2.3%)
General disorders
Fatigue (asthenia, lethargy, malaise)	2/37 (5.4%)		8/43 (18.6%)
Pain	1/37 (2.7%)		2/43 (4.7%)
Edema: limb	0/37 (0%)		1/43 (2.3%)
Fever	0/37 (0%)		2/43 (4.7%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/37 (0%)		3/43 (7%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils	1/37 (2.7%)		0/43 (0%)
Infection with unknown ANC	1/37 (2.7%)		0/43 (0%)
Infection with Grade 3 or 4 neutrophils	0/37 (0%)		1/43 (2.3%)
Infection with normal ANC or Grade 1 or 2 neutrophils	0/37 (0%)		5/43 (11.6%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	1/37 (2.7%)		4/43 (9.3%)
Mucositis/stomatitis (clinical exam)	1/37 (2.7%)		1/43 (2.3%)
Metabolism and nutrition disorders
Dehydration	2/37 (5.4%)		0/43 (0%)
Glucose, serum-high (hyperglycemia)	4/37 (10.8%)		6/43 (14%)
Phosphate, serum-low (hypophosphatemia)	4/37 (10.8%)		0/43 (0%)
Potassium, serum-low (hypokalemia)	2/37 (5.4%)		0/43 (0%)
Sodium, serum-low (hyponatremia)	3/37 (8.1%)		1/43 (2.3%)
Calcium, serum-low (hypocalcemia)	0/37 (0%)		1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Ataxia (incoordination)	1/37 (2.7%)		0/43 (0%)
Nervous system disorders
Syncope (fainting)	1/37 (2.7%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/37 (2.7%)		0/43 (0%)
Pneumonitis/pulmonary infiltrates	0/37 (0%)		3/43 (7%)
Vascular disorders
Hemorrhage, pulmonary/upper respiratory	0/37 (0%)		1/43 (2.3%)
Thrombosis/thrombus/embolism	0/37 (0%)		2/43 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.