Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00478426
• Collaborator: (none)
• Enrollment: 34
• Locations: 29
• Arm: 1
• Actual Duration (Months): 141.5
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well sunitinib malate works in treating patients with endometrial cancer that has come back after a period of improvement (recurrent) or has spread to other places in the body (metastatic). Sunitinib 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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma	Drug: Sunitinib Malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the objective response rate of recurrent or metastatic endometrial cancer to sunitinib (sunitinib malate).

2. To assess the frequency of prolonged stable disease (as defined by percentage [%] of patients alive and free from progressive disease at 6 months) in patients with recurrent or metastatic endometrial cancer treated with sunitinib.

SECONDARY OBJECTIVES:

1. To assess time-to- progression, median overall survival, and rate of one-year survival in patients with recurrent or metastatic endometrial cancer treated with sunitinib.

2. To assess the toxicity associated with sunitinib in patients with recurrent or metastatic endometrial cancer.

OUTLINE:

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up at 4 weeks and then every 3 months until relapse.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma
• Actual Study Start Date: Apr 30, 2007
• Actual Primary Completion Date: Feb 12, 2019
• Actual Study Completion Date: Feb 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (sunitinib malate) Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Sunitinib Malate; Given PO; Other Names: SU011248 SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate [Up to 7 years]

   Objective response rate, defined as the rate of complete or partial response as defined by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), disappearance of all target lesions.

Secondary Outcome Measures

1. Number of Participants With Prolonged Stable Disease [Up to 7 years]

   Described as the best response of stable disease that is maintained for atleast 6 months

2. Overall Survival [Up to 7 years]

   Estimated using the Kaplan-Meier method.

3. Number of Participants With Adverse Effects Assessed by CTCAE Version 3.0 [Up to 7 years]

   Number of participants that experience at east 1 adverse event while on trial, according to the CTCAE.

4. Time to Progression [Up to 7 years]

   The length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. Assessed by Kaplan and Meier method

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed endometrial cancer; adenocarcinoma (endometrioid and serous/papillary serous) and carcinosarcoma (ie. malignant mixed Mullerian tumor [MMMT]) of the uterus will be investigated; patients with other histologies (eg. squamous cell carcinoma or leiomyosarcoma) are excluded

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiotherapy, or radiofrequency ablation

• Previously treated patients must have evidence of progressive disease, either clinically or radiographically, as assessed by the investigator

• Eligible patients may have received no more than one prior cytotoxic chemotherapy regimen for recurrent, locally-advanced, or metastatic disease; if the prior chemotherapy was an anthracycline, they may have received no more than 6 cycles (or less than 450 mg/m^2 doxorubicin); patients must have completed any previous chemotherapy a minimum of 4 weeks (or 6 weeks if the regimen contained carmustine [BCNU] or mitomycin) prior to study registration; prior investigational treatment is permissible (as long as such treatment completed 4 weeks prior to registration)

• Life expectancy of greater than 3 months

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60)

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 100 g/dL

• Serum calcium =< 12.0 mg/dL (=< 3.0 mmol/L)

• Total serum bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Serum lipase =< 1.5 x institutional upper limit of normal

• Serum amylase =< 1.5 x institutional upper limit of normal

• Thyroid stimulating hormone (TSH)/T3/T4 within normal institutional limits

• Magnesium >= 0.5 mmol/L

• Patients must have corrected QT interval (QTc) < 500 msec

• The following group of patients are eligible provided they have normal baseline cardiac function (as determined by estimate of left ventricular ejection fraction [LVEF] on echocardiogram or multi-gated acquisition scan [MUGA]):

• Those with a history of congestive heart failure, provided they are no greater than New York Heart Association (NYHA) class I and on treatment at baseline

• Those with prior anthracycline exposure

• Those who have received prior central thoracic radiation that included the heart in the radiotherapy port

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery

• Patients may not be receiving any other investigational agents

• Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, vascular endothelial growth factor [VEGF] Trap, etc.) are ineligible

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib

• Patients who have a history of serious ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] equal to or greater than 3 beats in a row), QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded

• Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible

• Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5

• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded

• Patients with any of the following conditions are excluded:

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

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment

• Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry

• History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry

• History of pulmonary embolism within the past 12 months

• Class III or IV heart failure as defined by the NYHA functional classification system

• Pre-existing adrenal insufficiency (primary or secondary)

• The eligibility of patients taking medications that are potent inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) will be determined following a review of their case by the Principal Investigator; every effort should be made to switch patients taking such agents or substances to other medications, particularly patients who are taking enzyme-inducing anticonvulsant agents

• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible

• Patients with known brain metastases should be excluded

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with sunitinib malate

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
3	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
5	City of Hope South Pasadena	South Pasadena	California	United States	91030
6	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
7	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
8	Evanston Hospital CCOP	Evanston	Illinois	United States	60201
9	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
10	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
11	Loyola University Medical Center	Maywood	Illinois	United States	60153
12	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
13	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
14	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
15	Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard	Fort Wayne	Indiana	United States	46804
16	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
17	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
18	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
19	Oncology Care Associates PLLC	Saint Joseph	Michigan	United States	49085
20	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
21	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
22	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
23	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
24	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
25	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
26	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario	Canada	K1H 8L6
27	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
28	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
29	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Amit M Oza, University Health Network-Princess Margaret Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2016

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00478426
• Other Study ID Numbers: NCI-2009-00210; NCI-2009-00210; PHL-062; CDR0000513153; 7713; 7713; N01CM62201; N01CM62203; N01CM62209
• First Posted: May 24, 2007
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Carcinosarcoma; Mixed Tumor, Mullerian; Recurrence; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Period Title: Overall Study
STARTED	34
COMPLETED	33
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Overall Participants	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	34 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Canada	22 64.7%
United States	12 35.3%
Endometrioid Subtype (Count of Participants)
Count of Participants [Participants]	24 70.6%
Serous Subtype (Count of Participants)
Count of Participants [Participants]	6 17.6%
Carcinosarcoma Subtype (Count of Participants)
Count of Participants [Participants]	3 8.8%
Number of Lines of Previous Therapies (Count of Participants)
0 prior lines of therapy	9 26.5%
1 prior line of therapy	17 50%
2 prior lines of therapy	8 23.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	Objective response rate, defined as the rate of complete or partial response as defined by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), disappearance of all target lesions.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Of the 33 participants, only 28 were considered evaluable for response.

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Measure Participants	33
Partial Response	6 17.6%
Stable Disease	6 17.6%
Progressive Disease	16 47.1%
non-evaluable patient	5 14.7%

2. Secondary Outcome

Title	Number of Participants With Prolonged Stable Disease
Description	Described as the best response of stable disease that is maintained for atleast 6 months
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Of the 33 participants, 28 were considered evaluable for response. 5 of these patients were not fully evaluable for the study as they were removed before first radiological assessment but are nonetheless included in denominator for response assessment.

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Measure Participants	33
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Overall Survival
Description	Estimated using the Kaplan-Meier method.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Of the 33 participants, 28 were considered evaluable for response. 5 of these patients were not fully evaluable for the study as they were removed before first radiological assessment but are nonetheless included in denominator for response assessment.

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Measure Participants	33
Median (95% Confidence Interval) [months]	19.4

4. Secondary Outcome

Title	Number of Participants With Adverse Effects Assessed by CTCAE Version 3.0
Description	Number of participants that experience at east 1 adverse event while on trial, according to the CTCAE.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Of the 33 participants, 28 were considered evaluable for response. 5 of these patients were not fully evaluable for the study as they were removed before first radiological assessment but are nonetheless included in denominator for response assessment.

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Measure Participants	33
Count of Participants [Participants]	30 88.2%

5. Secondary Outcome

Title	Time to Progression
Description	The length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. Assessed by Kaplan and Meier method
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
Measure Participants	33
Median (95% Confidence Interval) [months]	3

Adverse Events

Time Frame	Adverse events were collected from baseline, onward to end of treatment up to 5 years total.
Arm/Group Title	Treatment (Sunitinib Malate)
Arm/Group Description	Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO
All Cause Mortality
	Treatment (Sunitinib Malate)
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Serious Adverse Events
	Treatment (Sunitinib Malate)
	Affected / at Risk (%)	# Events
Total	30/33 (90.9%)
Blood and lymphatic system disorders
Neutropenia	8/33 (24.2%)	8
Anemia	3/33 (9.1%)	3
Thrombocytopenia	3/33 (9.1%)	3
Cardiac disorders
Hypertension	6/33 (18.2%)	6
General disorders
Fatigue	14/33 (42.4%)	14
Other (Not Including Serious) Adverse Events
	Treatment (Sunitinib Malate)
	Affected / at Risk (%)	# Events
Total	30/33 (90.9%)
Gastrointestinal disorders
Diarrhea	25/33 (75.8%)	25
Dyspepsia	17/33 (51.5%)	17
Nausea	19/33 (57.6%)	19
General disorders
Oral Mucositis	17/33 (51.5%)	17

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.