Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00887809
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 47
• Location: 1
• Arm: 1
• Duration (Months): 67
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether an experimental drug called bevacizumab given together with gemcitabine and docetaxel, a standard chemotherapy regimen for sarcoma, can help sarcoma patients. This trial will examine what effects, good and/or bad the combination of gemcitabine, docetaxel and bevacizumab has on sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma; Leiomyosarcoma; Malignant Fibrous; Histiocytoma; Angiosarcoma	Drug: gemcitabine; Drug: docetaxel; Drug: bevacizumab	Phase 2

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: Phase II Trial Of Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: gemcitabine and docetaxel with bevacizumab Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.

Drug: gemcitabine; Drug: docetaxel; Drug: bevacizumab

Outcome Measures

Primary Outcome Measures

1. Overall Objective Response [6 months]

   Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed unresectable metastatic or locally recurrent leiomyosarcoma, Malignant Fibrous Histiocytoma (MFH, also known as high grade Undifferentiated Pleomorphic Sarcoma) pleomorphic liposarcoma, rhabdomyosarcoma or angiosarcoma.

• Zero to one prior chemotherapy regimens for metastatic disease. Prior adjuvant therapy will not count provided it was more than one year previously.

• Measurable disease as defined by RECIST

• Adequate performance status - ECOG 0 or 1

• Patients must be recovered from the toxic effects of prior chemotherapy or radiation. Therapy may not start until at least 3 weeks since prior cytotoxic chemotherapy, two weeks from completion of radiation therapy, and one week for patients on tyrosine kinase inhibitors or other targeted therapy.

• Age 18 To 75. As it is quite difficult to administer high dose docetaxel with gemcitabine, to the elderly, in order to protect patient safety, we will restrict eligibility to patients between the ages of 18 and 75.

• Adequate hematologic, hepatic and renal function as defined below

• Hemoglobin > or = to 8.0 g/dl

• Absolute neutrophil count > or = to 1,500/mm3

• Platelet count > or = to 100,000/mm3

• Total Bilirubin < or = to1.5 x upper limit of normal (ULN).

• ALT (SGOT) or AST (SGPT) < or = to 5 x ULN.

• Alkaline Phosphatase < or = to 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases.

• Serum creatinine 2.0 mg/dL

• Ability to understand informed consent and comply with treatment protocol

• Normal cardiac ejection fraction

• Urine protein:creatinine (UPC) ratio < than or = to 1.0 at screening

Exclusion Criteria:

• Uncontrolled intercurrent illness including infection or congestive heart failure within 6 months.

• Prior therapy with gemcitabine, docetaxel or bevacizumab

• Patients receiving other investigational agents

• Patients with known brain metastases

• Pregnancy or unwillingness to use effective birth control

• Patients with HIV disease will be permitted, only if they are on effective anti-retroviral therapy, have a CD4 count greater than 400, and have had no opportunistic infections within the past 6 months.

• Patients on anti-coagulation will be permitted if they are on a stable dose of warfarin or low-molecular weight heparin, and have had no major bleeds within the past 6 months.

• Inability to comply with study and/or follow-up procedures.

• Life expectancy of less than 12 weeks.

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study

• Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last three years

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg lasting > 24 hours on antihypertensive medications)

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection), requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1

• Symptomatic peripheral vascular disease

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

• Serious, non-healing wound, active ulcer, or non-healing bone fracture

• Proteinuria at screening as demonstrated by

• Urine protein:creatinine (UPC) ratio > or = to 1.0 at screening (patients discovered to have UPC ratio > or = to 1.0 at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

• Known hypersensitivity to any component of bevacizumab

• Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential

• History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3 months prior to study enrollment.

• Any history of stroke or transient ischemic attack within 6 months

• History of myocardial infarction or unstable angina within 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Genentech, Inc.

Investigators

• Principal Investigator: William Tap, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00887809
• Other Study ID Numbers: 09-015
• First Posted: Apr 24, 2009
• Last Update Posted: Jan 25, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: Bevacizumab (avastin); Gemcitabine; Taxotere (docetaxel); 09-015; Soft tissue
• Additional relevant MeSH terms: Sarcoma; Leiomyosarcoma; Hemangiosarcoma; Histiocytoma; Gemcitabine; Bevacizumab; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo
Arm/Group Description	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo
Period Title: Overall Study
STARTED	37	10
COMPLETED	33	10
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo	Total
Arm/Group Description	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo	Total of all reporting groups
Overall Participants	37	10	47
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 70.3%	7 70%	33 70.2%
>=65 years	11 29.7%	3 30%	14 29.8%
Sex: Female, Male (Count of Participants)
Female	22 59.5%	2 20%	24 51.1%
Male	15 40.5%	8 80%	23 48.9%

Outcome Measures

1. Primary Outcome

Title	Overall Objective Response
Description	Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo
Arm/Group Description	Gemcitabine, Docetaxel, Bevacizumab	Gemcitabine, Docetaxel, Placebo
Measure Participants	33	10
Complete Response (CR)	0 0%	1 10%
Partial Response (PR)	9 24.3%	1 10%
Stable Disease (SD)	23 62.2%	7 70%
Progression of Disease (POD)	1 2.7%	1 10%

Adverse Events

Arm/Group Title	Gemcitabine, Docetaxel, Bevacizumab		Gemcitabine, Docetaxel, Placebo
Arm/Group Description	Gemcitabine, Docetaxel, Bevacizumab		Gemcitabine, Docetaxel, Placebo
All Cause Mortality
	Gemcitabine, Docetaxel, Bevacizumab		Gemcitabine, Docetaxel, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gemcitabine, Docetaxel, Bevacizumab		Gemcitabine, Docetaxel, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/37 (32.4%)		6/10 (60%)
Blood and lymphatic system disorders
Hemoglobin	0/37 (0%)	0	2/10 (20%)	2
Hemorrhage/Bleeding, other	1/37 (2.7%)	1	0/10 (0%)	0
Leukocytes	0/37 (0%)	0	1/10 (10%)	1
Platelets	1/37 (2.7%)	1	2/10 (20%)	2
Cardiac disorders
Cardiac ischemia/infarction	0/37 (0%)	0	1/10 (10%)	1
Hypertension	1/37 (2.7%)	1	0/10 (0%)	0
Valvular heart disease	1/37 (2.7%)	1	0/10 (0%)	0
Gastrointestinal disorders
Colitis	0/37 (0%)	0	1/10 (10%)	1
General disorders
Death not assoc w CTCAE term- Death NOS	1/37 (2.7%)	1	0/10 (0%)	0
Febrile neutropenia	0/37 (0%)	0	1/10 (10%)	1
Pain - Chest/thorax NOS	1/37 (2.7%)	1	0/10 (0%)	0
Pain - Extremity-limb	1/37 (2.7%)	1	0/10 (0%)	0
Pain - Pelvis	0/37 (0%)	0	2/10 (20%)	2
Syncope (fainting)	1/37 (2.7%)	1	0/10 (0%)	0
Infections and infestations
Infection normal Absolute Neutrophil Counts/grade 1/2 neutrophils-Cellulitis(skin)	1/37 (2.7%)	1	0/10 (0%)	0
Infection normal Absolute Neutrophil Counts/grade 1/2 neutrophils-Pneumonia(lung)	1/37 (2.7%)	1	0/10 (0%)	0
Infection unknown Absolute Neutrophil Counts -Pneumonia(lung)	0/37 (0%)	0	1/10 (10%)	1
Infection, other	2/37 (5.4%)	2	0/10 (0%)	0
Nervous system disorders
Confusion	0/37 (0%)	0	1/10 (10%)	1
Renal and urinary disorders
Renal/Genitourinary-Other	0/37 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	0/37 (0%)	0	1/10 (10%)	1
Pulmonary/upper respiratory - Other	0/37 (0%)	0	1/10 (10%)	1
Pulmonary hypertension	1/37 (2.7%)	1	0/10 (0%)	0
Thrombosis/thrombus/embolism	1/37 (2.7%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Gemcitabine, Docetaxel, Bevacizumab		Gemcitabine, Docetaxel, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/37 (89.2%)		10/10 (100%)
Blood and lymphatic system disorders
ALT, SGPT	10/37 (27%)	10	3/10 (30%)	3
AST, SGOT	10/37 (27%)	10	0/10 (0%)	0
Hemoglobin	27/37 (73%)	27	8/10 (80%)	8
International normalized ratio (INR)	0/37 (0%)	0	1/10 (10%)	1
Leukocytes (total WBC)	20/37 (54.1%)	20	5/10 (50%)	5
Lymphopenia	16/37 (43.2%)	16	6/10 (60%)	6
Neutrophils/granulocytes	22/37 (59.5%)	22	5/10 (50%)	5
Platelets	9/37 (24.3%)	9	3/10 (30%)	3
Partial thromboplastin time (PTT)	0/37 (0%)	0	1/10 (10%)	1
General disorders
Edema: limb	3/37 (8.1%)	3	1/10 (10%)	1
Fatigue (asthenia, lethargy, malaise)	3/37 (8.1%)	3	2/10 (20%)	2
Mucositis (Clincal exam)- Oral cavity	3/37 (8.1%)	3	0/10 (0%)	0
Infections and infestations
Infection normal Absolute Neutrophil Counts/grade 1/2 neutrophils-Pneumonia(lung)	0/37 (0%)	0	1/10 (10%)	1
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	19/37 (51.4%)	19	6/10 (60%)	6
Alkaline phosphatase	5/37 (13.5%)	5	1/10 (10%)	1
Bilirubin (hyperbilirubinemia)	3/37 (8.1%)	3	1/10 (10%)	1
Creatinine	0/37 (0%)	0	1/10 (10%)	1
Glucose, high (hyperglycemia)	17/37 (45.9%)	17	4/10 (40%)	4
Glucose, low (hypoglycemia)	3/37 (8.1%)	3	0/10 (0%)	0
Magnesium, high (hypermagnesemia)	2/37 (5.4%)	2	0/10 (0%)	0
Phosphate, low (hypophosphatemia)	11/37 (29.7%)	11	3/10 (30%)	3
Potassium, high (hyperkalemia)	3/37 (8.1%)	3	1/10 (10%)	1
Potassium, low (hypokalemia)	4/37 (10.8%)	4	2/10 (20%)	2
Sodium, low (hyponatremia)	2/37 (5.4%)	2	2/10 (20%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	0/37 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Rash: erythema multiforme	0/37 (0%)	0	1/10 (10%)	1

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.