Mechanistic Evaluation on Sorafenib Induced Hypophosphatemia.

Mechanistic Evaluations on Sorafenib Induced Hypophosphatemia in Patients With Advanced Renal Cell Carcinoma

The purpose of this study is to:

1. To elucidate the mechanism involved in the sorafenib-induced hypophosphatemia and possible early effect of hypophosphatemia on bone mineral density
2. A secondary objective to assess the effect sorafenib treatment on evaluate left ventricular function (LVEF) and Beta-type natriuretic peptide in plasma.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Sorafenib (Nexavar, BAY43-9006)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
  • Florida
    • Jacksonville, Florida, United States, 32224
  • Illinois
    • Maywood, Illinois, United States, 60153
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
  • New York
    • Stony Brook, New York, United States, 11794-944

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >/= 18 years
• Histologically or cytologically confirmed advanced RCC
• Evaluable disease with lesions measured by CT-scan or MRI according to modified Response Evaluation Criteria in Solid Tumors (RECIST)
• ECOG Performance Status of 0 or 1

• Adequate bone marrow, liver and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

  • Hemoglobin > 9.0 g/dL 1. Age greater Than 18 yrs old
  • Absolute neutrophil count (ANC) > 1,500/mm3
  • Platelet count 100,000/mm3
  • Total bilirubin <= 1.5 times the upper limit of normal
  • ALT and AST <= 2.5 x upper limit of normal (<= 5 x upper limit of normal for patients with liver involvement of their cancer)
  • Amylase and lipase < 1.5 x the upper limit of normal
  • PT-INR/PTT 1.5 x ULN (Patients who are being prophylactically anti-coagulated with an agent such as coumadin or low molecular weight heparin or therapeutically anti-coagulated with LMWH will be allowed to participate provided that they meet these criteria; in addition, these patients must be monitored at appropriate intervals throughout study)
  • Serum creatinine < 2.0 x the upper limit of normal or creatinine clearance (CrCl) 45 mL/min (CrCl = Wt (kg) (140-age)/72 Cr level, female 0.85) for patients with creatinine levels above 2.0 x ULN
  • Phosphate 2.0 mg/dl
  • LVEF >/= 40%
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Negative results must be available prior to study treatment
• Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 day period after last study drug dosing. The investigator should advise the patient how to achieve adequate contraception
• Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

• Patients who meet the following criteria at the time of screening will be excluded:

  • History of cardiac disease: congestive heart failure >NYHA Class 2; hospitalization for CHF symptoms in the 6 months prior to study entry; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
  • Known history of HIV infection or chronic hepatitis B or C
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
  • Active clinically serious infections (> Grade 2 CTCAE v3)
  • Known history or presence of metastatic brain or meningeal tumors (head CT or MRI at screening to confirm)
  • Patients with seizure disorder requiring medication (such as steroids or anti epileptics)
  • History of organ allograft
  • Patients undergoing renal dialysis
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
  • Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry. Anticancer therapy is defined as any agent or combination of agents with clinically proven anticancer activity administered by any route with the purpose of affecting the cancer, either directly or indirectly, including palliative and therapeutic endpoints
  • Radiotherapy to target lesions within 4 weeks of start of study drug
  • Major surgery within 4 weeks of start of study
  • Serious, non-healing wound, ulcer, or bone fracture
  • Investigational drug therapy within 4 weeks of study entry
  • Prior exposure to sorafenib
  • Pregnant or breast-feeding patients
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  • Unable to swallow oral medications
  • Any malabsorption condition
  • Current treatment with bisphosphonates therapy or prior therapy with such agents within 12 weeks of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Sorafenib (Nexavar, BAY43-9006); Sorafenib will be administered at 400mg BID for a 28 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate a potential mechanism of hypophosphatemia related to sorafenib treatment based on measurement of phosphate regulating factors, peptides, and related laboratory variables	Occur when the last query is resolved

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effect of sorafenib treatment on left ventricular ejection fraction (LVEF) and B-type Natriuretic Peptide (BNP) in plasma	Occur when the last query is resolved

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: February 13, 2008
• First Submitted That Met QC Criteria: February 13, 2008
• First Posted (Estimate): February 25, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2014
• Last Update Submitted That Met QC Criteria: December 17, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Sorafenib; Hypophosphatemia; Left ventricular ejection fraction (LVEF); Beta-type Natriuretic Peptide (BNP)
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Phosphorus Metabolism Disorders; Carcinoma, Renal Cell; Carcinoma; Hypophosphatemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 12345 (Other Grant/Funding Number: Reasons for Hope Fund in Prevention and Early Detection of Mental Illness)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No