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Carfilzomib in Refractory Renal Cell Carcinoma (RCC)

Primary Purpose

Kidney Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Carfilzomib

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring Kidney Cancer, Refractory Renal Cell Carcinoma, RCC, Clear cell kidney cancer with metastatic disease, Carfilzomib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
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.
Age >/= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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.
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
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)
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
Creatinine clearance (CrCl) >/= 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
Written informed consent in accordance with federal, local, and institutional guidelines.
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
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:

Brain metastases not controlled with surgery, whole brain radiotherapy, or with stereotactic radiosurgery
Systemic therapy within two weeks of treatment initiation
Pregnant or lactating females
Major surgery within 21 days prior to beginning study treatment
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to beginning study treatment
Known human immunodeficiency virus infection
Active hepatitis B or C infection
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
Uncontrolled hypertension (defined by BP consistently > 150/100) or uncontrolled diabetes (defined by HbA1c > 8.5) within 14 days prior to beginning study treatment
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
Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to beginning study treatment
Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
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
Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to beginning study treatment
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

Sites / Locations

University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carfilzomib

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) of Carfilzomib Therapy in Participants With Refractory Or Intolerant to Prior Therapy

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

Overall Response Rate (ORR)

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.

Overall Survival (OS)

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

Safety of Carfilzomib

Reason for stopping therapy

PFS and ORR as a Function of VHL Mutation Subtype

Full Information

NCT ID

NCT01775930

First Posted

January 23, 2013

Last Updated

February 21, 2020

Sponsor

M.D. Anderson Cancer Center

Collaborators

Onyx Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01775930

Brief Title

Carfilzomib in Refractory Renal Cell Carcinoma (RCC)

Official Title

Phase II Study of Carfilzomib in Patients With Refractory Renal Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

October 2013 (Actual)

Primary Completion Date

January 18, 2019 (Actual)

Study Completion Date

January 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

Onyx Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney Cancer

Keywords

Kidney Cancer, Refractory Renal Cell Carcinoma, RCC, Clear cell kidney cancer with metastatic disease, Carfilzomib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Carfilzomib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Carfilzomib

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS) of Carfilzomib Therapy in Participants With Refractory Or Intolerant to Prior Therapy

Description

Time Frame

The number of months from enrollment to progression of cancer or death, whichever comes first up to 4 months

Secondary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

Time Frame

Participants response was evaluated every 8 weeks from the first dose of carfilzomib until progression od disease (PD), up to 4 months

Title

Overall Survival (OS)

Description

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

Time Frame

15 months

Title

Safety of Carfilzomib

Description

Reason for stopping therapy

Time Frame

4 months

Title

PFS and ORR as a Function of VHL Mutation Subtype

Time Frame

No data collected

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) 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. Age >/= 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 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. 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 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) 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 Creatinine clearance (CrCl) >/= 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault) Written informed consent in accordance with federal, local, and institutional guidelines. 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 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: Brain metastases not controlled with surgery, whole brain radiotherapy, or with stereotactic radiosurgery Systemic therapy within two weeks of treatment initiation Pregnant or lactating females Major surgery within 21 days prior to beginning study treatment Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to beginning study treatment Known human immunodeficiency virus infection Active hepatitis B or C infection 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 Uncontrolled hypertension (defined by BP consistently > 150/100) or uncontrolled diabetes (defined by HbA1c > 8.5) within 14 days prior to beginning study treatment 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 Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to beginning study treatment Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) 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 Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to beginning study treatment 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric Jonasch, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31439537

Citation

Hasanov E, Tidwell RSS, Fernandez P, Park L, McMichael C, Tannir NM, Jonasch E. Phase II Study of Carfilzomib in Patients With Refractory Renal Cell Carcinoma. Clin Genitourin Cancer. 2019 Dec;17(6):451-456. doi: 10.1016/j.clgc.2019.07.003. Epub 2019 Jul 23.

Results Reference

derived

Links:

URL

http://www.mdanderson.org

Description

UT MD Anderson Cancer Center Website

Learn more about this trial

Carfilzomib in Refractory Renal Cell Carcinoma (RCC)

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