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Sorafenib, Gemcitabine, and Capecitabine in Treating Patients With Unresectable and/or Metastatic Kidney Cancer

Primary Purpose

Recurrent Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Gemcitabine Hydrochloride
Sorafenib Tosylate
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Renal Cell Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Patients must have histologically or cytologically confirmed renal cell carcinoma that is unresectable and/or metastatic; patients with collecting duct carcinoma, oncocytomas, or transitional cell carcinoma are not eligible; patients with sarcomatoid renal cell carcinoma are eligible, but those with pure sarcomas are not; histologic documentation of metastatic disease is not required; clinical confirmation, but not pathologic staging, of metastatic disease is required 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 Patients may have received one prior immunotherapy based regimen (i.e. interleukin-2 or interferon alpha) ending >= 4 weeks prior to enrollment Patients may have received up to 2 prior regimens containing mitogen-activated protein kinases (MAPK), vascular endothelial growth factor (VEGF) pathway inhibitors (e.g. sunitinib or bevacizumab) and/or mammalian target of rapamycin (mTOR) inhibitor (e.g. temsirolimus) ending >= 4 weeks prior to enrollment Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) =< 2 OR Karnofsky >= 60% Leukocytes >= 3000/uL Absolute neutrophil count >= 1,500/uL Platelet count >= 100,000/uL Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x IULN Creatinine =< 1.5 x IULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal The effects of sorafenib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing 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; 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 may not have received prior chemotherapy; if patients have had prior definitive or other surgery, prior radiation therapy, they must have fully recovered from the effects of therapy with at least 4 weeks recovery time; for patients who have had a surgical biopsy only, they must have simply recovered Patients may not be receiving any other investigational agents Patients with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; previously treated brain metastases are allowed if they show no evidence of progression on CT or magnetic resonance imaging (MRI) at least 8 weeks after completion of surgery and/or radiotherapy History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib, gemcitabine and capecitabine No concurrent megestrol is permitted; no megestrol therapy within 4 weeks prior to protocol treatment is allowed; no concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, phenobarbitol or carbamazepine), rifampin, or St. John's wort Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary disease including asthma, chronic bronchitis, emphysema with requirements for chronic oxygen use or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because sorafenib is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued if the mother is treated with sorafenib; the potential risks may apply to other agents used in this study Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with sorafenib, gemcitabine, or capecitabine administered during the study; appropriate studies will be undertaken in patients receiving combination ant-retroviral therapy when indicated Any swallowing dysfunction leading to difficulty taking the investigational therapy or capecitabine Prior treatment with sorafenib Patients with any history or evidence of a bleeding diathesis Patients on therapeutic anticoagulation with coumarins (e.g. warfarin); prophylactic coumarin-based anticoagulation (i.e. low dose warfarin) for venous or arterial access devices is allowed provided that the requirements for prothrombin time (PT), international normalization ratio (INR) and/or partial thromboplastin time (PTT) are met; prophylactic or therapeutic low molecular weight heparin is allowed; patients with known brain metastases are excluded (even if treated and stable) if they are also on therapeutic doses of anticoagulation Patients with known dihydropyrimidine dehydrogenase deficiency

Sites / Locations

  • Montefiore Medical Center - Moses Campus
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • Mount Sinai Hospital
  • Weill Medical College of Cornell University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib + Gemcitabine + Capecitabine

Arm Description

Patients receive sorafenib* PO BID on days 1-21, gemcitabine IV over 30 minutes on days 1 and 8, and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for at least 3 courses in the absence of unacceptable toxicity or disease progression.

Outcomes

Primary Outcome Measures

Objective Response for BAY 43-9006 in Combination With Gemcitabine and Capecitabine Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR

Secondary Outcome Measures

Median Number of Months of Progression Free Survival (PFS)
PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Number of Participants Who Survived (Overall Survival)
Overall survival (OS) is defined as the time from start of treatment to death from any cause.

Full Information

First Posted
July 19, 2005
Last Updated
March 17, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00121251
Brief Title
Sorafenib, Gemcitabine, and Capecitabine in Treating Patients With Unresectable and/or Metastatic Kidney Cancer
Official Title
A Phase I/II Trial of BAY 43-9006 Plus Gemcitabine and Capecitabine in the Treatment of Patients With Advanced Renal Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
June 3, 2005 (Actual)
Primary Completion Date
March 14, 2017 (Actual)
Study Completion Date
March 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I/II trial is studying the side effects and best dose of sorafenib, gemcitabine, and capecitabine and to see how well they work in treating patients with unresectable and/or metastatic kidney cancer. Sorafenib 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. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with gemcitabine and capecitabine may kill more tumor cells.
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of sorafenib administered in combination with gemictabine and capecitabine in patients with advanced renal cell carcinoma. II. Determine the objective response rate for sorafenib in combination with gemictabine and capecitabine in patients with advanced renal cell carcinoma. III. Determine the duration of overall survival and progression free survival in these patients. OUTLINE: This is a multicenter, non-randomized, phase I dose-escalation study followed by a phase II study. PHASE I: Patients receive sorafenib* orally (PO) twice daily (BID) on days 1-21, gemcitabine intravenously (IV) over 30 minutes on days 1 and 8, and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for at least 3 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of sorafenib, gemcitabine, and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Note: *Patients who complete at least 3 courses of treatment with objective response or stable disease but are deemed poor candidates for continued chemotherapy may continue treatment with sorafenib PHASE II: Patients receive sorafenib 200mg orally twice a day on days 1-21, gemcitabine 750 mg/m2 intravenously on days 1 & 8, and capecitabine 415 mg/m2 orally twice a day on days 1-14 of each 21 day cycle, as in phase I at the MTD determined in phase I. After completion of study treatment patients are followed periodically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib + Gemcitabine + Capecitabine
Arm Type
Experimental
Arm Description
Patients receive sorafenib* PO BID on days 1-21, gemcitabine IV over 30 minutes on days 1 and 8, and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for at least 3 courses in the absence of unacceptable toxicity or disease progression.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Sorafenib Tosylate
Other Intervention Name(s)
BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective Response for BAY 43-9006 in Combination With Gemcitabine and Capecitabine Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR
Time Frame
Up to 9 years
Secondary Outcome Measure Information:
Title
Median Number of Months of Progression Free Survival (PFS)
Description
PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Time Frame
From the time of the patient's initial best response (PR or CR) until documented progression, assessed up to 9 years
Title
Number of Participants Who Survived (Overall Survival)
Description
Overall survival (OS) is defined as the time from start of treatment to death from any cause.
Time Frame
Up to 9 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed renal cell carcinoma that is unresectable and/or metastatic; patients with collecting duct carcinoma, oncocytomas, or transitional cell carcinoma are not eligible; patients with sarcomatoid renal cell carcinoma are eligible, but those with pure sarcomas are not; histologic documentation of metastatic disease is not required; clinical confirmation, but not pathologic staging, of metastatic disease is required 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 Patients may have received one prior immunotherapy based regimen (i.e. interleukin-2 or interferon alpha) ending >= 4 weeks prior to enrollment Patients may have received up to 2 prior regimens containing mitogen-activated protein kinases (MAPK), vascular endothelial growth factor (VEGF) pathway inhibitors (e.g. sunitinib or bevacizumab) and/or mammalian target of rapamycin (mTOR) inhibitor (e.g. temsirolimus) ending >= 4 weeks prior to enrollment Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) =< 2 OR Karnofsky >= 60% Leukocytes >= 3000/uL Absolute neutrophil count >= 1,500/uL Platelet count >= 100,000/uL Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x IULN Creatinine =< 1.5 x IULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal The effects of sorafenib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing 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; 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 may not have received prior chemotherapy; if patients have had prior definitive or other surgery, prior radiation therapy, they must have fully recovered from the effects of therapy with at least 4 weeks recovery time; for patients who have had a surgical biopsy only, they must have simply recovered Patients may not be receiving any other investigational agents Patients with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; previously treated brain metastases are allowed if they show no evidence of progression on CT or magnetic resonance imaging (MRI) at least 8 weeks after completion of surgery and/or radiotherapy History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib, gemcitabine and capecitabine No concurrent megestrol is permitted; no megestrol therapy within 4 weeks prior to protocol treatment is allowed; no concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, phenobarbitol or carbamazepine), rifampin, or St. John's wort Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary disease including asthma, chronic bronchitis, emphysema with requirements for chronic oxygen use or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because sorafenib is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued if the mother is treated with sorafenib; the potential risks may apply to other agents used in this study Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with sorafenib, gemcitabine, or capecitabine administered during the study; appropriate studies will be undertaken in patients receiving combination ant-retroviral therapy when indicated Any swallowing dysfunction leading to difficulty taking the investigational therapy or capecitabine Prior treatment with sorafenib Patients with any history or evidence of a bleeding diathesis Patients on therapeutic anticoagulation with coumarins (e.g. warfarin); prophylactic coumarin-based anticoagulation (i.e. low dose warfarin) for venous or arterial access devices is allowed provided that the requirements for prothrombin time (PT), international normalization ratio (INR) and/or partial thromboplastin time (PTT) are met; prophylactic or therapeutic low molecular weight heparin is allowed; patients with known brain metastases are excluded (even if treated and stable) if they are also on therapeutic doses of anticoagulation Patients with known dihydropyrimidine dehydrogenase deficiency
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Tagawa
Organizational Affiliation
Montefiore Medical Center - Moses Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Sorafenib, Gemcitabine, and Capecitabine in Treating Patients With Unresectable and/or Metastatic Kidney Cancer

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