Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00238121
• Collaborator: (none)
• Enrollment: 56
• Locations: 7
• Arm: 1
• Duration (Months): 64.9
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying how well sorafenib works in treating patients with advanced or recurrent uterine cancer.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Uterine Sarcoma; Stage III Uterine Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma	Drug: sorafenib tosylate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the objective response rate in patients with advanced or recurrent uterine cancer treated with sorafenib.

2. Determine the toxic effects of this drug in these patients.

SECONDARY OBJECTIVES:

1. Determine progression-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (carcinoma vs carcinosarcoma).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of BAY 43-9006 in Advanced/Recurrent Uterine Carcinoma/Carcinosarcoma
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN

Outcome Measures

Primary Outcome Measures

1. Objective Overall Response Rate [Up to 5 years]

   Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.

Secondary Outcome Measures

1. Overall Survival [Up to 5 years]

   Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive.

2. Progression Free Survival [Up to 5 years]

   Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions.

3. Duration of Response [Up to 5 years]

   Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• No prior sorafenib

• Histologically or cytologically confirmed uterine carcinoma or carcinosarcoma:

• Advanced or recurrent disease

• Not amenable to curative surgery or radiotherapy

• Measurable disease:

• At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan

• Tumor tissue block must be available

• No known brain metastases

• Performance status:

• ECOG 0-2 OR

• Karnofsky 60-100%

• Hematopoietic:

• Absolute neutrophil count >= 1,500/mm3

• Platelet count >= 100,000/mm3

• No bleeding diathesis

• Hepatic:

• Bilirubin normal

• AST and ALT =< 2.5 times upper limit of normal

• Renal:

• Creatinine =< 1.5 mg/dL OR

• Creatinine clearance >= 60 mL/min

• Cardiovascular:

• No uncontrolled hypertension, defined by 1 of the following:

• Blood pressure > 150/100 mm Hg

• Currently taking > 1 antihypertensive agent

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other active malignancy

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance

• No swallowing dysfunction that would preclude study drug ingestion

• No other uncontrolled illness

• Prior biological response modifier therapy allowed

• No prior antiangiogenesis therapy

• No prior MAPK-signaling agents

• No prior vascular endothelial growth factor receptor (VEGFR) inhibitors

• No more than 1 prior chemotherapy regimen

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• Prior hormonal therapy allowed

• Prior radiotherapy allowed provided the only site of measurable disease was not located within the radiation port OR disease has progressed since completion of therapy

• Recovered from all prior therapy

• Concurrent warfarin allowed provided all of the following are true:

• Patient is therapeutic on a stable warfarin dose

• INR target range =< 3

• Patient is monitored with weekly INR testing

• No active bleeding or pathological condition that carries a high bleeding risk

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)

• No concurrent rifampin

• No concurrent Hypericum perforatum (St. John's wort)

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• More than 4 weeks since prior radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	University of Southern California	Los Angeles	California	United States	90033-0804
3	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
4	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	60702
5	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
6	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
7	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Gini Fleming, University of Chicago Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00238121
• Other Study ID Numbers: NCI-2009-00068; 13572A; CDR0000445181; N01CM62203
• First Posted: Oct 13, 2005
• Last Update Posted: Nov 20, 2015
• Last Verified: Jan 1, 2014

• Additional relevant MeSH terms: Sarcoma; Carcinosarcoma; Mixed Tumor, Mullerian; Recurrence; Sorafenib

Study Results

Participant Flow

Recruitment Details	The study population consisted of patients at least 18 years old with advanced or recurrent carcinoma, or uterine carcinosarcoma. Both cohorts received a starting dose of 400 mg sorafenib orally twice daily on a continuous basis.
Pre-assignment Detail	A Simon optimal two-stage design was used with objective response rate as the primary efficacy endpoint.

Arm/Group Title	Carcinoma	Carcinosarcoma
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	40	16
COMPLETED	37	14
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Carcinoma	Carcinosarcoma	Total
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	40	16	56
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	64
Sex: Female, Male (Count of Participants)
Female	40 100%	16 100%	56 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Non-Hispanic white	29 72.5%	10 62.5%	39 69.6%
Hispanic	4 10%	1 6.3%	5 8.9%
African-American	2 5%	3 18.8%	5 8.9%
Asian	5 12.5%	2 12.5%	7 12.5%
Histology (participants) [Number]
Adenocarcinoma (unspecified)	12 30%	0 0%	12 21.4%
Serous	3 7.5%	0 0%	3 5.4%
Clear cell	1 2.5%	0 0%	1 1.8%
Endometrioid	24 60%	0 0%	24 42.9%
Carcinosarcoma	0 0%	16 100%	16 28.6%

Outcome Measures

1. Primary Outcome

Title	Objective Overall Response Rate
Description	Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carcinoma	Carcinosarcoma
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	37	14
Number [participants]	2 5%	0 0%

2. Secondary Outcome

Title	Overall Survival
Description	Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carcinoma	Carcinosarcoma
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	38	14
Median (95% Confidence Interval) [Month]	11.4	5

3. Secondary Outcome

Title	Progression Free Survival
Description	Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carcinoma	Carcinosarcoma
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	38	14
Median (95% Confidence Interval) [Month]	3.2	1.8

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carcinoma	Carcinosarcoma
Arm/Group Description	Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	2	0
Mean (Full Range) [Month]	25

Adverse Events

Arm/Group Title	Sorafenib
Arm/Group Description
All Cause Mortality
	Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	11/56 (19.6%)
Blood and lymphatic system disorders
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	1/56 (1.8%)
Gastrointestinal disorders
Fistula, GI : Colon/cecum/appendix	1/56 (1.8%)
Hemorrhage, GI : Esophagus	1/56 (1.8%)
Hemorrhage, GI : Lower GI NOS	1/56 (1.8%)
Pain : Abdomen NOS	1/56 (1.8%)
General disorders
Death not associated with CTCAE term : Disease progression NOS	2/56 (3.6%)
Fatigue (asthenia, lethargy, malaise)	1/56 (1.8%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/56 (1.8%)
Infection with unknown ANC : Bladder (urinary)	1/56 (1.8%)
Infection with unknown ANC : Lung (pneumonia)	2/56 (3.6%)
Infection with unknown ANC : Urinary tract NOS	1/56 (1.8%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	2/56 (3.6%)
Metabolism and nutrition disorders
Dehydration	1/56 (1.8%)
Phosphate, serum-low (hypophosphatemia)	1/56 (1.8%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)	1/56 (1.8%)
Pain : Joint	1/56 (1.8%)
Renal and urinary disorders
Hemorrhage, GU : Bladder	1/56 (1.8%)
Hemorrhage, GU : Ureter	1/56 (1.8%)
Reproductive system and breast disorders
Fistula, GU : Vagina	1/56 (1.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/56 (1.8%)
Pneumonitis/pulmonary infiltrates	1/56 (1.8%)
Vascular disorders
Hypertension	1/56 (1.8%)
Thrombosis/thrombus/embolism	1/56 (1.8%)
Other (Not Including Serious) Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	56/56 (100%)
Blood and lymphatic system disorders
Hemoglobin	21/56 (37.5%)
Leukocytes (total WBC)	12/56 (21.4%)
Cardiac disorders
Supraventricular and nodal arrhythmia : Sinus tachycardia	3/56 (5.4%)
Gastrointestinal disorders
Constipation	16/56 (28.6%)
Diarrhea	24/56 (42.9%)
Flatulence	4/56 (7.1%)
Heartburn/dyspepsia	4/56 (7.1%)
Hemorrhage, GI : Rectum	5/56 (8.9%)
Mucositis/stomatitis (functional/symptomatic) : Oral cavity	13/56 (23.2%)
Nausea	20/56 (35.7%)
Pain : Abdomen NOS	24/56 (42.9%)
Vomiting	12/56 (21.4%)
General disorders
Edema: limb	10/56 (17.9%)
Fatigue (asthenia, lethargy, malaise)	27/56 (48.2%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	6/56 (10.7%)
Investigations
Alkaline phosphatase	16/56 (28.6%)
ALT, SGPT (serum glutamic pyruvic transaminase)	13/56 (23.2%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	18/56 (32.1%)
Bicarbonate, serum-low	5/56 (8.9%)
Bilirubin (hyperbilirubinemia)	4/56 (7.1%)
INR (International Normalized Ratio of prothrombin time)	5/56 (8.9%)
Lymphopenia	14/56 (25%)
Neutrophils/granulocytes (ANC/AGC)	4/56 (7.1%)
Platelets	7/56 (12.5%)
Weight loss	14/56 (25%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	13/56 (23.2%)
Anorexia	25/56 (44.6%)
Calcium, serum-high (hypercalcemia)	6/56 (10.7%)
Calcium, serum-low (hypocalcemia)	14/56 (25%)
Glucose, serum-high (hyperglycemia)	10/56 (17.9%)
Glucose, serum-low (hypoglycemia)	3/56 (5.4%)
Phosphate, serum-low (hypophosphatemia)	15/56 (26.8%)
Potassium, serum-low (hypokalemia)	15/56 (26.8%)
Sodium, serum-low (hyponatremia)	11/56 (19.6%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) : Extraocular	5/56 (8.9%)
Pain : Back	11/56 (19.6%)
Pain : Bone	3/56 (5.4%)
Pain : Extremity-limb	5/56 (8.9%)
Pain : Joint	9/56 (16.1%)
Pain : Muscle	9/56 (16.1%)
Nervous system disorders
Dizziness	4/56 (7.1%)
Neuropathy: sensory	5/56 (8.9%)
Pain : Head/headache	5/56 (8.9%)
Psychiatric disorders
Insomnia	7/56 (12.5%)
Mood alteration : Anxiety	3/56 (5.4%)
Renal and urinary disorders
Proteinuria	3/56 (5.4%)
Respiratory, thoracic and mediastinal disorders
Cough	9/56 (16.1%)
Dyspnea (shortness of breath)	8/56 (14.3%)
Hemorrhage, pulmonary/upper respiratory : Nose	3/56 (5.4%)
Hemorrhage, pulmonary/upper respiratory : Respiratory tract NOS	3/56 (5.4%)
Pain : Larynx	4/56 (7.1%)
Urinary frequency/urgency	3/56 (5.4%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	3/56 (5.4%)
Skin and subcutaneous tissue disorders
Dry skin	10/56 (17.9%)
Hair loss/alopecia (scalp or body)	16/56 (28.6%)
Pruritus/itching	4/56 (7.1%)
Rash/desquamation	26/56 (46.4%)
Rash: acne/acneiform	18/56 (32.1%)
Rash: hand-foot skin reaction	20/56 (35.7%)
Sweating (diaphoresis)	3/56 (5.4%)
Vascular disorders
Hot flashes/flushes	4/56 (7.1%)
Hypertension	18/56 (32.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.