Carfilzomib in Refractory Renal Cell Carcinoma (RCC)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01775930
• Collaborator: Onyx Therapeutics, Inc. (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 63.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of this clinical research study is learn if carfilzomib can help control kidney cancer. The safety of this drug will also be studied.

Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells cannot repair themselves, this may cause them to die.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: Carfilzomib	Phase 2

Detailed Description

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive carfilzomib 2 days a week for the first 3 weeks of each 4-week study cycle (Days 1, 2, 8, 9, 15, and 16 of each cycle). Each dose is given by vein over about 30 minutes.

Before you receive the study drug, you will be given dexamethasone to help decrease the risk of side effects during the first cycle. You may ask the study staff for information about how the drugs are given and their risks.

During Cycle 1, you will receive extra fluid (saline) by vein before each dose of study drug. This is part of standard clinical care. This will also be done during Cycle 2, if the study doctor thinks it is needed.

You will remain in the clinic for an extra hour after receiving each dose during Cycle 1 and after the first dose of Cycle 2, to receive additional fluids by vein.

If you have any side effects from the drug, tell the study doctor right away. The study doctor may then lower the dose or keep the dose level the same.

Each study cycle is 4 weeks.

Study Visits:

Weeks 1, 2, and 3 of each cycle:

• Your vital signs and weight will be measured.

• Blood (about 3 teaspoons) will be drawn for routine tests

Every 4 weeks (+/-4 days):

• Your medical history will be recorded.

• You will have a physical exam, including measurement of your vital signs and weight.

• You will be asked about any drugs or treatments you may be receiving and any side effects that you have had.

• Your performance status will be recorded.

• Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood sugar level and your pancreatic function, if the study doctor thinks it is needed. You will be asked to fast (not eat, and drink only water) for at least 8 hours before this blood draw.

Every 8 weeks (+/-7 days):

• You will have an x-ray of chest, CT scan of the chest and abdomen, and MRI scan of the brain to check the status of the disease. If the doctor thinks it is needed, you will also have a bone scan.

• If you can become pregnant, you will have a blood (about 2 teaspoons) pregnancy test.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, intolerable side effects occur, or you are not able to follow study directions.

End-of-Treatment Visit:

About 30 days after your last dose of the study drug:

• You will have a physical exam, including measurement of your vital signs and weight.

• You will be asked about any drugs or treatments you may be receiving and any side effects that you have had.

• Blood (about 3 teaspoons) will be drawn for routine and blood sugar tests.

• You will have an x-ray, CT scan, and MRI scan to check the status of the disease.

Long-Term Follow-up:

After you stop taking the study drug, the study staff will check your health status every 6 months for the rest of your life. The study staff will collect this information by either checking your medical record, emailing you, or calling you on the telephone. Each call should only last about 5 minutes.

This is an investigational study. Carfilzomib is FDA approved and commercially available in treatment of multiple myeloma. The use of carfilzomib in kidney cancer is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Carfilzomib in Patients With Refractory Renal Cell Carcinoma
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jan 18, 2019
• Actual Study Completion Date: Jan 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carfilzomib Patients receive Carfilzomib at dose of 20 mg/m2 over 30 minutes by vein infusion on Days 1 and 2 and a dose of 56 mg/m2 over 30 minutes by vein infusion on Days 8, 9, 15, and 16 of each 4 week cycle.	Drug: Carfilzomib; 20 mg/m2 over 30 minutes by vein infusion on Days 1 and 2 and a dose of 56 mg/m2 over 30 minutes by vein infusion on Days 8, 9, 15, and 16 of each 4 week cycle.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) of Carfilzomib Therapy in Participants With Refractory Or Intolerant to Prior Therapy [The number of months from enrollment to progression of cancer or death, whichever comes first up to 4 months]

   Progression free survival defined as time from enrollment to progression or death, whichever comes first. Progression defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Any patients who are alive and free of disease at time of analysis censored at date of most recent tumor assessment.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Participants response was evaluated every 8 weeks from the first dose of carfilzomib until progression od disease (PD), up to 4 months]

   The number of participants had a complete response (CR, complete reduction in tumor burden) or partial response (PR, a reduction in tumor burden of at least 30%) as determined for radiographic imaging such as a CT scan. Participants who do not have a reduction in tumor burden will either have stable disease (SD) or progressive disease (PD, which is an increase in tumor burden of at least 20%). The results are based on the best response that each participant achieved while on treatment.

2. Overall Survival (OS) [15 months]

   The number of months from the time of enrollment until death per participant

3. Safety of Carfilzomib [4 months]

   Reason for stopping therapy

4. PFS and ORR as a Function of VHL Mutation Subtype [No data collected]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Biopsy proven clear cell kidney cancer with metastatic disease. Progressive disease or intolerance to at least one but not more than three (3) prior systemic therapy(ies)

2. 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 for non-nodal lesions and short axis for nodal lesions) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan.

3. Age >/= 18 years

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

5. Adequate hepatic function with serum ALT and AST </= 3.0 times the upper limit of normal and serum direct and total bilirubin </= 1.5 times the upper limit of normal.

6. Absolute neutrophil count (ANC) >/= 1.0 × 10^{9/L; patients with an ECOG performance status of 2 at study entry must have an ANC >/= 1.5 x 10}9/L

7. Hemoglobin >/= 8 g/dL (80 g/L) within 14 days prior to beginning study treatment (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines); Patients with an ECOG performance status of 2 at study entry must have a hemoglobin >/= 9 g/dL (transfusion assistance acceptable)

8. Platelet count >/= 50 × 10^{9/L; Patients with an ECOG performance status of 2 at study entry must have a platelet count >/= 100 × 10}9/L

9. Creatinine clearance (CrCl) >/= 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault)

10. Written informed consent in accordance with federal, local, and institutional guidelines.

11. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception during the study and for a period of 6 weeks after you stop receiving the study drug

12. Male subjects must agree to practice contraception during the study and for a period of 6 weeks after you stop receiving the study drug

Exclusion Criteria:

1. Brain metastases not controlled with surgery, whole brain radiotherapy, or with stereotactic radiosurgery

2. Systemic therapy within two weeks of treatment initiation

3. Pregnant or lactating females

4. Major surgery within 21 days prior to beginning study treatment

5. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to beginning study treatment

6. Known human immunodeficiency virus infection

7. Active hepatitis B or C infection

8. Unstable angina or myocardial infarction within 4 months prior to beginning study treatment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker

9. Uncontrolled hypertension (defined by BP consistently > 150/100) or uncontrolled diabetes (defined by HbA1c > 8.5) within 14 days prior to beginning study treatment

10. Nonhematologic malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas

11. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to beginning study treatment

12. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)

13. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

14. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to beginning study treatment

15. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

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
• Onyx Therapeutics, Inc.

Investigators

• Principal Investigator: Eric Jonasch, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 9, 2014

More Information

Additional Information:

• UT MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01775930
• Other Study ID Numbers: 2012-0694; NCI-2013-02350
• First Posted: Jan 25, 2013
• Last Update Posted: Mar 4, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Kidney Cancer; Refractory Renal Cell Carcinoma; RCC; Clear cell kidney cancer with metastatic disease; Carfilzomib
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms

Study Results

Participant Flow

Recruitment Details	This was a single arm, single-center, non-randomized study of carfilzomib in participants with refractory ccRCC. Participants were accrued over a period of 195 days.

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Overall Participants	9
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	59
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 11.1%
Not Hispanic or Latino	8 88.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 88.9%
More than one race	0 0%
Unknown or Not Reported	1 11.1%
Region of Enrollment (participants) [Number]
United States	9 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants)
ECOG PS 0	6 66.7%
ECOG PS 1	2 22.2%
ECOG PS 2	1 11.1%
Memorial Sloan Kettering Cancer Center (MSKCC) Risk Factor (Count of Participants)
Good	1 11.1%
Intermediate	6 66.7%
Poor	2 22.2%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) of Carfilzomib Therapy in Participants With Refractory Or Intolerant to Prior Therapy
Description	Progression free survival defined as time from enrollment to progression or death, whichever comes first. Progression defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Any patients who are alive and free of disease at time of analysis censored at date of most recent tumor assessment.
Time Frame	The number of months from enrollment to progression of cancer or death, whichever comes first up to 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Measure Participants	9
Median (95% Confidence Interval) [Months]	1.8

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	The number of participants had a complete response (CR, complete reduction in tumor burden) or partial response (PR, a reduction in tumor burden of at least 30%) as determined for radiographic imaging such as a CT scan. Participants who do not have a reduction in tumor burden will either have stable disease (SD) or progressive disease (PD, which is an increase in tumor burden of at least 20%). The results are based on the best response that each participant achieved while on treatment.
Time Frame	Participants response was evaluated every 8 weeks from the first dose of carfilzomib until progression od disease (PD), up to 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Measure Participants	9
Complete response (CR)	0 0%
Partial response (PR)	0 0%
Stable disease (SD)	3 33.3%
Progression of disease (PD)	6 66.7%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	The number of months from the time of enrollment until death per participant
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Measure Participants	9
Median (95% Confidence Interval) [Months]	13.2

4. Secondary Outcome

Title	Safety of Carfilzomib
Description	Reason for stopping therapy
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Measure Participants	9
Progressive disease	9 100%
Toxicity	0 0%
Patient decision	0 0%

5. Secondary Outcome

Title	PFS and ORR as a Function of VHL Mutation Subtype
Time Frame	No data collected

Outcome Measure Data

Analysis Population Description

The futility stopping rule was meet due to the low response rate to the treatment. None of our patients had a better response than stable disease (SD). Consequently the correlative analyses were not performed for VHL mutation subtype only for PFS and ORR which is reported as Outcomes.

Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
Measure Participants	0

Adverse Events

Time Frame	Adverse events will be followed for 30 days beyond discontinuation of treatment for any reason; duration of treatment up to 4 months. All-Cause Mortality will be assessed up to 15 months.
Arm/Group Title	Carfilzomib Treatment
Arm/Group Description	Dosed with 20 mg/mm2 infused on Day 1 and 2. Dosed with 56 mg/mm2 infused on Day 8, 9, 15, and 16.
All Cause Mortality
	Carfilzomib Treatment
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Serious Adverse Events
	Carfilzomib Treatment
	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)
Blood and lymphatic system disorders
Anemia	1/9 (11.1%)
Lymphocyte count decreased	1/9 (11.1%)
General disorders
Fatigue	2/9 (22.2%)
Investigations
BUN elevated	1/9 (11.1%)
Metabolism and nutrition disorders
Hyperuricemia	1/9 (11.1%)
Renal and urinary disorders
Acute kidney injury	2/9 (22.2%)
Creatinine increased	2/9 (22.2%)
Proteinuria	1/9 (11.1%)
Vascular disorders
Hypertension	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Carfilzomib Treatment
	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)
Blood and lymphatic system disorders
Anemia	6/9 (66.7%)
Lymphocyte count decreased	6/9 (66.7%)
Neutrophil count decreased	2/9 (22.2%)
Platelet count decreased	4/9 (44.4%)
White blood cell decreased	4/9 (44.4%)
Gastrointestinal disorders
Constipation	2/9 (22.2%)
Diarrhea	2/9 (22.2%)
Nausea	2/9 (22.2%)
Oral pain	1/9 (11.1%)
Vomiting	1/9 (11.1%)
General disorders
Chills	3/9 (33.3%)
Edema	2/9 (22.2%)
Fatigue	3/9 (33.3%)
Fever	3/9 (33.3%)
Pain	1/9 (11.1%)
Investigations
Alanine aminotransferase increased	1/9 (11.1%)
Alkaline phosphatase increased	2/9 (22.2%)
Aspartate aminotransferase increased	1/9 (11.1%)
BUN elevated	1/9 (11.1%)
Metabolism and nutrition disorders
Anorexia	3/9 (33.3%)
Hypercalcemia	1/9 (11.1%)
Hyperglycemia	2/9 (22.2%)
Hyperkalemia	2/9 (22.2%)
Hyperuricemia	1/9 (11.1%)
Hypoalbuminemia	1/9 (11.1%)
Hypomagnesemia	4/9 (44.4%)
Hyponatremia	1/9 (11.1%)
Nervous system disorders
Headache	3/9 (33.3%)
Paresthesia	1/9 (11.1%)
Renal and urinary disorders
Creatinine increased	6/9 (66.7%)
Hemoglobinuria	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/9 (33.3%)
Dyspnea	5/9 (55.6%)
Productive cough	1/9 (11.1%)
Upper respiratory infection	1/9 (11.1%)
Skin and subcutaneous tissue disorders
Alopecia	1/9 (11.1%)
Pruritus	1/9 (11.1%)
Rash maculo-papular	2/9 (22.2%)
Vascular disorders
Hypertension	1/9 (11.1%)

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.