Sunitinib Malate in Refractory Germ Cell Tumors

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00912912
• Collaborator: Pfizer (Industry)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 67
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if Sutent® (sunitinib malate, SU011248) can control the disease in patients with germ cell tumors that are resistant to earlier treatment.

Condition or Disease	Intervention/Treatment	Phase
Genitourinary Disease	Drug: Sunitinib Malate	Phase 2

Detailed Description

The Study Drug:

Sunitinib malate is designed to block pathways that control important events such as the growth of blood vessels that are essential for the growth of cancer.

Within 14 days of enrollment on this study, you will have the following tests and procedures performed:

• Your complete medical history will be recorded.

• You will have a physical exam.

Within 7 days of enrollment on this study, you will have the following tests and procedures performed:

-Blood (about 3 teaspoons) and urine will be collected for routine testing and to test for certain biomarkers (to check the status of the disease).

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take sunitinib malate capsules once a day (by mouth) for 4 weeks in a row followed by 2 weeks with no study drug. These 6 weeks are considered 1 cycle of study treatment.

Study Visits:

On Day 1 of each cycle (about every 6 weeks), you will have the following tests done before you take the study drug:

• You will have a physical exam.

• You will be asked about how you are feeling and about any side effects you have experienced since your last visit.

• You will have blood (about 3 teaspoons) and urine collected for routine tests and to test for certain biomarkers.

For the first 4 weeks of treatment, you should have your blood pressure monitored. This may be done at your home with a digital pressure device, or you may visit your local doctor for this testing.

About Day 21 of Cycles 1 and 2, blood (about 2- 3 teaspoons) will be drawn for routine tests. This may be done at your local doctor's office and results faxed to the study doctor.

On Day 1 of Cycle 2, Day 1 of Cycle 3, and then Day 1 of every 2 cycles after that (Cycle 5, Cycle 7, and so on), you will have imaging scans to check status of the disease. This could include CT or MRI scans, an ECG, and a chest x-ray. If your doctor thinks it is necessary, you may have additional imaging scans at any time.

On Day 1 of every other cycle (Cycle 3, Cycle 5, and so on), you will have an echocardiogram or MUGA scan.

Length of Study:

You may remain on study for as long as you are benefitting. You will be taken off study if intolerable side effects occur or if the disease gets worse. However, if the disease gets worse very quickly during Cycles 1 or 2, you will be taken off study at that time.

Off-Study Visit:

When you are taken off of treatment on this study, the following tests and procedures will be performed:

• You will have a physical exam.

• You will be asked how you are feeling and about any changes in your medical history since beginning this study.

• You will also be asked about any side effects you have experienced since your last visit.

This is an investigational study. Sunitinib malate is approved by the FDA for the treatment of adults with kidney cancer. Its use in patients with germ cell tumors is investigational. Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Sunitinib Malate in Refractory Germ Cell Tumors
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sunitinib Malate Sunitinib Malate 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.	Drug: Sunitinib Malate; 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.; Other Names: SU011248 Sutent

Outcome Measures

Primary Outcome Measures

1. 12 Week Progression Free Survival Rate in Refractory Germ Cell Tumors Treated With Sunitinib Malate [12 weeks]

   Measurable disease or response recorded from start of treatment until disease progression/recurrence. Participants who die during therapy or are lost to follow-up shall be counted as progressive disease. Progressive disease defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Evaluation of measurable disease response follows Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Progressive metastatic Germ-cell tumors (GCTs) of gonadal or extragonadal origin in males after failure of front-line therapy and at least one salvage regimen.

2. Must have evaluable or measurable disease by clinical or radiological studies. Alternatively, in the absence of radiologically evaluable or measurable disease, two sequentially rising marker values each one week apart attributed by treating physician to germ cell tumor is permitted; either beta human chorionic gonadotropin (hCG) above 50 mIU/ml and/or alpha-fetoprotein (AFP) above 20 ng/ml qualifies as eligible.

3. The Eastern Cooperative Oncology Group (ECOG) Performance Score 0-2

4. Adequate organ function as follows: Calculated creatinine clearance >/= 35cc/min, Absolute neutrophil count >/= 1500/mm^{3, hemoglobin >/= 8 g/dL, serum calcium </= 12 mg/dL, Platelet count >/= 75,000/mm}3, AST (SGOT)/ALT (SGPT) < 2.5 x upper limit of normal (ULN), Total bilirubin < 2.0mg/dl.

5. Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 grade </= 2.

6. At least 18 years of age as safety of sunitinib in a pediatric population has not been established.

7. Able to provide informed consent

8. Must be able to ingest oral medication

9. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.

10. Patients who have not received prior high-dose chemotherapy and stem cell rescue as salvage therapy will have this option discussed with them. Only patients ineligible, unwilling or unable to undertake this option will be eligible for this trial.

Exclusion Criteria:

1. NCI CTCAE Version 3.0 grade 3 hemorrhage within the 4 weeks prior to starting the study treatment.

2. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.

3. Patients with history of Long QT syndrome.

4. Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade >/= 2.

5. Uncontrolled Hypertension (> 140/90 mm Hg despite optimal medical therapy).

6. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.

7. Symptomatic bowel obstruction.

8. Prior VEGFR/PDGFR inhibitor therapy.

9. Known human immunodeficiency virus infection, chronic active hepatitis or liver cirrhosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Pfizer

Investigators

• Study Chair: Lance Pagliaro, MD, BA, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00912912
• Other Study ID Numbers: 2006-0685; NCI-2012-01645
• First Posted: Jun 3, 2009
• Last Update Posted: Apr 15, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Genitourinary; Testis; Refractory Germ Cell Tumors; Advanced germ cell tumors; GCTs; Sunitinib Malate; Sutent; SU011248
• Additional relevant MeSH terms: Neoplasms, Germ Cell and Embryonal; Sunitinib

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 29, 2009 to July 29, 2010. All recruitment was done at The University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Study was closed early due to low rate of response and slow accrual.

Arm/Group Title	Sunitinib Malate
Arm/Group Description	Sunitinib Malate 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.
Period Title: Overall Study
STARTED	5
COMPLETED	1
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Sunitinib Malate
Arm/Group Description	Sunitinib Malate 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 20%
White	3 60%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	12 Week Progression Free Survival Rate in Refractory Germ Cell Tumors Treated With Sunitinib Malate
Description	Measurable disease or response recorded from start of treatment until disease progression/recurrence. Participants who die during therapy or are lost to follow-up shall be counted as progressive disease. Progressive disease defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Evaluation of measurable disease response follows Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib Malate
Arm/Group Description	Sunitinib Malate 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.
Measure Participants	5
Number [Percentage of Participants]	20 400%

Adverse Events

Time Frame	Adverse event collection through each cycle, defined as a planned 6-week treatment interval (cycle) with participants to complete at least 2 cycles of therapy unless evidence of rapid disease progression.
Arm/Group Title	Sunitinib Malate
Arm/Group Description	Sunitinib Malate 50 mg capsules once a day (by mouth) for 4 weeks in a row in a 6 week cycle.
All Cause Mortality
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
General disorders
PAIN (LEFT-CHEST)	1/5 (20%)	1
DEATH	1/5 (20%)	1
WEAKNESS	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
PAIN (MID-BACK)	1/5 (20%)	1
PAIN (THORACIC BACK)	1/5 (20%)	1
Nervous system disorders
HEADACHE	1/5 (20%)	1
Vascular disorders
HEMORRHAGE	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
HEMOGLOBIN	4/5 (80%)	9
PLATELETS	3/5 (60%)	4
NEUTROPHILS/GRANULOCYTES	3/5 (60%)	3
LYMPHOPENIA	1/5 (20%)	2
LEUKOCYTES	4/5 (80%)	6
Cardiac disorders
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA	2/5 (40%)	2
Endocrine disorders
HYPOTHYROIDISM	1/5 (20%)	1
ENDOCRINE - OTHER	1/5 (20%)	1
Gastrointestinal disorders
CONSTIPATION	2/5 (40%)	7
NAUSEA	3/5 (60%)	5
VOMITING	2/5 (40%)	7
PAIN (ABDOMEN)	3/5 (60%)	4
ANOREXIA	2/5 (40%)	5
DIARRHEA	2/5 (40%)	3
ULCER - GI	1/5 (20%)	1
GASTROINTESTINAL - OTHER	1/5 (20%)	1
MUCOSITIS/STOMATITIS	4/5 (80%)	13
General disorders
FATIGUE	4/5 (80%)	17
INSOMNIA	1/5 (20%)	1
PAIN (OTHER)	2/5 (40%)	3
WEIGHT LOSS	1/5 (20%)	1
PAIN (CHEST/THORAX)	2/5 (40%)	2
Metabolism and nutrition disorders
HYPOMAGNESEMIA	2/5 (40%)	2
PROTEINURIA	2/5 (40%)	2
CREATININE	1/5 (20%)	1
HYPERBILIRUBINEMIA	1/5 (20%)	5
HYPERGLYCEMIA	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
PAIN (EXTREMITY - LIMB)	2/5 (40%)	2
PAIN (BACK)	2/5 (40%)	2
MUSCULOSKELETAL/SOFT TISSUE - OTHER	1/5 (20%)	1
Nervous system disorders
NEUROPATHY: SENSORY	4/5 (80%)	5
HEADACHE	1/5 (20%)	1
NEUROLOGY - OTHER	1/5 (20%)	2
Psychiatric disorders
MOOD ALTERATION (DEPRESSION)	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	1/5 (20%)	1
DYSPNEA	2/5 (40%)	4
Skin and subcutaneous tissue disorders
ALOPECIA	2/5 (40%)	2
RASH/DESQUAMATION	3/5 (60%)	4
HYPOPIGMENTATION	2/5 (40%)	4
BRUISING	1/5 (20%)	1
DRY SKIN	1/5 (20%)	2

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.