Mechanistic Evaluation on Sorafenib Induced Hypophosphatemia.

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00622479
First received: February 13, 2008
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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.

Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Sorafenib (Nexavar, BAY43-9006)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Mechanistic Evaluations on Sorafenib Induced Hypophosphatemia in Patients With Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • To evaluate a potential mechanism of hypophosphatemia related to sorafenib treatment based on measurement of phosphate regulating factors, peptides, and related laboratory variables [ Time Frame: Occur when the last query is resolved ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the effect of sorafenib treatment on left ventricular ejection fraction (LVEF) and B-type Natriuretic Peptide (BNP) in plasma [ Time Frame: Occur when the last query is resolved ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: May 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib will be administered at 400mg BID for a 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00622479

Locations
United States, Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Jacksonville, Florida, United States, 32224
United States, Illinois
Maywood, Illinois, United States, 60153
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, New York
Stony Brook, New York, United States, 11794-944
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00622479     History of Changes
Other Study ID Numbers: 12345
Study First Received: February 13, 2008
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Sorafenib
Hypophosphatemia
Left ventricular ejection fraction (LVEF)
Beta-type Natriuretic Peptide (BNP)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Hypophosphatemia
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Metabolic Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Phosphorus Metabolism Disorders
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014