Genitourinary Cancer, Kidney Cancer
Conditions
Keywords
Genitourinary Cancer, Kidney Cancer, Metastatic Renal Cell Carcinoma, mRCC, Sunitinib, Sunitinib malate, SUO11248, Sutent, Questionnaire, Survey
Brief summary
The goal of this clinical research study is to learn more about the safety of giving sunitinib to patients with metastatic kidney cancer for 2 weeks followed by 1 week in which they receive no drug. Researchers want to learn more about the side effects of the drug and the effects of a different dosing schedule.
Detailed description
Study Drug Administration: If you are found to be eligible to take part in this study, you will take sunitinib capsules by mouth every day for 2 weeks, followed by 1 week in which you do not receive any study drug. This will then be repeated every 3 weeks. Every 6 weeks will be 1 study cycle. If you have any side effects tell the study doctor right away. The study doctor may change your dose of the study drug. Study Visits: Every day during the first week, and then at least 1 time each week during the study, your blood pressure will be checked (either at home, at the clinic, or by your local doctor). You will need to write down your blood pressure in a blood pressure diary each time you check it and bring the diary with you to each clinic visit. On Day 1 of Cycle 1: * You will have a physical exam. * Blood (about 3-4 tablespoons) will be drawn for routine and biomarker testing. * You will fill out a questionnaire about the quality of your life and about how you are feeling. This should take about 5 minutes. On Day 42 of every cycle: * You will have a physical exam. * Blood (about 3-4 tablespoons) will be drawn for routine tests. On Day 42 of every even-numbered cycle (Cycles 2, 4, 6, and so on): * You will have a CT scan of your chest, abdomen, and pelvis. * Blood (about 1 tablespoon) will be drawn to check your thyroid function. * Blood (about 2 tablespoons) will be drawn for biomarker testing. (Cycles 2 , 4, and 6 only) * You will fill out the questionnaire about the quality of your life and about how you are feeling. (Cycles 2 , 4, and 6 only) At any time that the doctor thinks it is needed, additional blood (about 1 tablespoon) may be drawn to check your thyroid function, and you may need to have a bone scan and CT scan or MRI of the brain to check the status of the disease. Length of Study: You may continue taking the study drug for as long as the study doctor thinks it is in your best interest. You will be taken off treatment if the disease gets worse, intolerable side effects occur, or if you are unable to follow study directions. Your participation in this study will be over after the follow-up visit. However, the study team may perform a medical record review or follow-up call to check on how you are doing. If you are called, this should last about 5-10 minutes. End-of-Treatment Visit: After you are no longer receiving the study drug, you will have an end-of-treatment visit. You will have a physical exam and blood (about 3-4 tablespoons) will be drawn for routine and biomarker testing. End-of- Treatment Follow-Up Visit: About 30 days after your end-of-treatment visit you will have a follow-up visit and the following procedures will be performed: * You will have a physical exam. * Blood (about 3-4 tablespoons) will be drawn for routine tests. * You will have CT scans of your chest, abdomen and pelvis to check the status of the disease. This is an investigational study. Sunitinib is FDA approved and commercially available to treat advanced kidney cancer. The dosing schedule being used on this study is investigational. Up to 60 participants will be enrolled in this study. Up to 60 may take part at MD Anderson.
Interventions
DRUGSunitinib
Starting dose: 50 mg by mouth daily given for 2 weeks on followed by 1 week off. 1 cycle is 6 weeks.
BEHAVIORALQuestionnaire
Questionnaire completion on Day 1 of Cycle 1, and on Day 35 of Cycles 2, 4, and 6.
Sponsors
Pfizer
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically-confirmed metastatic renal cell carcinoma of clear cell histology. Prior nephrectomy is not a requirement for eligibility 2. Age \>/=18 years 3. Measurable or evaluable metastatic disease per RECIST v 1 4. ECOG performance status 0-1 5. Normal organ and bone marrow function as defined by: Serum aspartate transaminase (AST) or serum glutamic oxaloacetic transaminase (SGOT) and serum alanine transaminase (ALT) or serum glutamic pyruvic transaminase (SGPT) \</= 2.5 x laboratory upper limit of normal (ULN); Total serum bilirubin \</= 2.0 x ULN; Absolute neutrophil count (ANC) \>/= 1500/µL; Platelets \>/= 100,000/µL; Hemoglobin \>/= 9.0 g/dL (transfusion permitted); Serum calcium \</= 12.0 mg/dL; Serum creatinine \</= 2.5 mg/dL 6. Patients with a history of deep venous thromboembolism or pulmonary embolism on treatment with anticoagulation are eligible for the study. 7. Subjects must have the ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
1. Prior treatment with sunitinib or any other systemic therapy in the metastatic setting (prior neo/adjuvant therapy will be allowed if completed \> 6 months prior to registration and therapy not discontinued for toxicity) 2. Uncontrolled hypertension (defined as blood pressure \>140/90 mm Hg not controlled with anti-hypertensives) 3. Prior intraabdominal, intrathoracic, vascular, spinal or intracranial surgery or radiation therapy within 4 weeks of starting treatment 4. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis 5. New York Heart Association (NYHA) grade II or greater congestive heart failure 6. Current treatment on another therapeutic clinical trial 7. Any of the following within the preceding 6 months- myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass, graft, cerebrovascular accident or transient ischemic attack, clinically significant bleeding 8. Pregnant or breastfeeding women are excluded from this study because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib. Breastfeeding must be discontinued if the mother is treated with sunitinib 9. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness 10. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Toxicity | Participants were monitored for toxicities for 30 days after treatment was discontinued; total treatment duration approximately 34 months | Determine the number of participants who experience a specific, treatment-related adverse events at a grade three, four or five: fatigue, hand-foot syndrome, and/or diarrhea. Adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 17 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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 |
| The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Participants were monitored for toxicities for 30 days after treatment was discontinued or until death, whichever occurred first. | Adverse events as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4 |
| Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities | 2 years | Reported as the number and percentage of participants who underwent one or more dose reductions, as well as, the number and percentage of participants whose treatment ended. |
| Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | 36 weeks from the start of treatment | Participants completed FACT-G suveys evaluating quality of life at weeks 0, 12, 24, and 36. The score range is from 0 to 180 with higher scores reflecting a better quality of life. The results were reported for each time point for all participants and then broken into two groups: participants with a grade 3 toxicity and participants without a grade 3 toxicity. The total number of surveys changes as the weeks progress. |
| Changes in Circulating DNA Levels With Antiangiogenic Treatment | Not applicable due data not generated due to timing and budgetary issues | — |
Countries
United States
Participant flow
Recruitment details
Sixty participants enrolled between August 2014 and March 2016. Participants recruited from The University of Texas MD Anderson Cancer Center, Cleveland Clinic Foundation, Fox Chase Cancer Center, and University of North Carolina Lineberger Cancer Center). All participants had confirmed treatment naive metastatic clear cell renal cell carcinoma.
Pre-assignment details
One participant did not take the study medication due to declining mental health status before the first dose was initiated. Consequently, only 59 patients were included in the final analysis.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Sunitinib starting dose 50 mg by mouth daily given for 2 weeks on followed by 1 week off. 1 cycle is 6 weeks.
Sunitinib: Starting dose: 50 mg by mouth daily given for 2 weeks on followed by 1 week off. 1 cycle is 6 weeks.
Questionnaire: Questionnaire completion on Day 1 of Cycle 1, and on Day 35 of Cycles 2, 4, and 6. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Sunitinib |
|---|---|
| Age, Continuous | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 53 Participants |
| Memorial Sloan Kettering Cancer Center (MSKCC) Risk Factor Good | 13 Participants |
| Memorial Sloan Kettering Cancer Center (MSKCC) Risk Factor Intermediate | 40 Participants |
| Memorial Sloan Kettering Cancer Center (MSKCC) Risk Factor Poor | 6 Participants |
| Memorial Sloan Kettering Cancer Center (MSKCC) Risk Factor Unknown | 1 Participants |
| Metastatic Sites Bone | 3 Participants |
| Metastatic Sites Liver | 8 Participants |
| Metastatic Sites Lung | 39 Participants |
| Metastatic Sites Lymph node | 10 Participants |
| Metastatic Sites Other | 29 Participants |
| Number of Metastatic Sites | 2 Number of metastatic sites |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 50 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 59 |
| other Total, other adverse events | 59 / 59 |
| serious Total, serious adverse events | 35 / 59 |
Outcome results
Primary
Rate of Toxicity
Determine the number of participants who experience a specific, treatment-related adverse events at a grade three, four or five: fatigue, hand-foot syndrome, and/or diarrhea. Adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4
Time frame: Participants were monitored for toxicities for 30 days after treatment was discontinued; total treatment duration approximately 34 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alternating Sunitinib | Rate of Toxicity | Grade>=3, of all 3 adverse events | 15 Participants |
| Alternating Sunitinib | Rate of Toxicity | Fatigue, Grade >=3 | 8 Participants |
| Alternating Sunitinib | Rate of Toxicity | Diarrhea, Grade >=3 | 5 Participants |
| Alternating Sunitinib | Rate of Toxicity | Hand-foot syndrome, Grade >=3 | 3 Participants |
Secondary
Changes in Circulating DNA Levels With Antiangiogenic Treatment
Time frame: Not applicable due data not generated due to timing and budgetary issues
Population: Data were not collected due to timing and budgetary issues.
Secondary
Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G)
Participants completed FACT-G suveys evaluating quality of life at weeks 0, 12, 24, and 36. The score range is from 0 to 180 with higher scores reflecting a better quality of life. The results were reported for each time point for all participants and then broken into two groups: participants with a grade 3 toxicity and participants without a grade 3 toxicity. The total number of surveys changes as the weeks progress.
Time frame: 36 weeks from the start of treatment
Population: The number of surveys collected at week 0, 12,24, and 36 are 54, 49, 44, and 35 surveys.The number of surveys with a grade 3 toxicity collected at week 0, 12, 24, and 36 are 14, 11, 12, and 10 surveys. The number of surveys without a grade 3 toxicity collected at week 0, 12, 24, and 36 are 40, 38, 32, and 25 surveys.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | All Participants- week 0 | 87.8 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | All Participants- week 12 | 88 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | All Participants- week 24 | 86 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | All Participants- week 36 | 89 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | Grade 3 tox - week 0 | 86.8 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | Grade 3 tox - week 12 | 79.5 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | Grade 3 tox - week 24 | 79 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | Grade 3 tox - week 36 | 83 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | No grade 3 tox - week 0 | 88.8 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | No grade 3 tox - week 12 | 89.8 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | No grade 3 tox - week 24 | 91.8 Score on a scale |
| Alternating Sunitinib | Changes in Participant Reported Outcomes in the Functional Assessment of Cancer Therapy-General (FACT-G) | No grade 3 tox - week 36 | 93.8 Score on a scale |
Secondary
Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities
Reported as the number and percentage of participants who underwent one or more dose reductions, as well as, the number and percentage of participants whose treatment ended.
Time frame: 2 years
Population: Out of the 59 participants only 29 encountered a dose reduction. The number of dose reductions a participant experienced was also reported with the percentage being based on the 29 participants who had a reduction.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alternating Sunitinib | Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities | 1 Dose Reduction | 7 Participants |
| Alternating Sunitinib | Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities | 2 Dose Reductions | 14 Participants |
| Alternating Sunitinib | Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities | 3 Dose Reductions | 3 Participants |
| Alternating Sunitinib | Dose Reductions and Treatment Discontinuations Due to Unacceptable Toxicities | 4 Dose Reductions | 5 Participants |
Secondary
Progression-Free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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
Time frame: 17 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alternating Sunitinib | Progression-Free Survival (PFS) | 13.7 months |
Secondary
The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event
Adverse events as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4
Time frame: Participants were monitored for toxicities for 30 days after treatment was discontinued or until death, whichever occurred first.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Vomiting | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | White blood cell decreased | 4 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Any grade ≥3 event | 35 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Alkaline phosphatase increased | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Anemia | 6 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Dehydration | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Diarrhea | 5 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Fatigue | 8 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Pancreatic insufficiency | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Headache | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Hypertension | 16 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Hyponatremia | 2 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Hypophosphatemia | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Lymphocyte count decreased | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Mucositis oral | 5 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Gout | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Neutrophil count decreased | 8 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Hand-foot syndrome | 3 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Platelet count decreased | 2 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Thromboembolic event | 3 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Urticaria | 1 Participants |
| Alternating Sunitinib | The Number and Percentage of Participants Who Experienced a Grade 3, 4, or 5 Adverse Event | Vascular access complication | 1 Participants |