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Phase II Trial of Sorafenib (BAY 43-9006) (IND 69896; NSC 724772) in Patients With Advanced Urothelial Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Regional Transitional Cell Cancer of the Renal Pelvis and Ureter, Squamous Cell Carcinoma of the Bladder, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder, Urethral Cancer Associated With Invasive Bladder Cancer

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Trial Information

Phase II Trial of Sorafenib (BAY 43-9006) (IND 69896; NSC 724772) in Patients With Advanced Urothelial Cancer


PRIMARY OBJECTIVES:

I. To evaluate the 4-month progression-free survival rate, response rate and toxicity of BAY
43-9006 in patients with progressing regional or metastatic transitional cell carcinoma (or
mixed histologies containing a component of TCC) of the urothelium who have progressed on
one and only one prior systemic chemotherapy regimen for metastatic disease.

SECONDARY OBJECTIVES:

I. To determine the time to disease progression and overall survival with BAY 43-9006.

II. To evaluate the frequency of polymorphisms in drug metabolizing enzymes and to correlate
these polymorphisms with variations in BAY 43-9006 pharmacokinetics.

III. To evaluate the frequency of raf kinase mutations in tumor specimens and correlate
these with response rate.

IV. To evaluate serum VEGF levels as potential markers of angiogenesis inhibition by BAY
43-9006.

V. To evaluate markers of apoptosis and kinase inhibition in peripheral blood mononuclear
cells as potential biomarkers of BAY 43-9006 activity.

VI. To determine if there are proteins differentially translated from the genome in patients
who respond to treatment with BAY 43-9006 versus patients who do not respond to BAY 43-9006.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until 2 years from
study entry and then every 6 months until 3 years from study entry.


Inclusion Criteria:



- Histologically confirmed transitional cell carcinoma or mixed histologies containing
a component of transitional cell carcinoma of the urothelium (renal pelvis, ureter,
bladder, urethra) with manifestations of progressing regional or metastatic cancer;
or (2) Nontransitional cell histologies include patients with adenocarcinoma or
squamous cell carcinomas representing greater than 90% of specimen; patients with
small cell carcinoma, soft tissue sarcomas, or carcinosarcomas are excluded

- Measurable disease, as defined in the RECIST criteria; all sites of disease must be
evaluated within 4 weeks prior to registration

- Patients must have progressed on one and only one prior systemic chemotherapy for
metastatic disease; prior chemotherapy administered in the adjuvant or neoadjuvant
setting is permitted (i.e. does not count as 1 prior regimen) provided that it was
completed greater than 12 months prior to the start of the first chemotherapy regimen
administered in the metastatic setting

- Patients must not have had prior systemic biologic response modifier therapy;
patients must not have had chemotherapy, hormonal or biologic therapy within 4 weeks
(6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have
recovered from adverse events due to agents administered more than 4 weeks earlier

- Prior radiotherapy is allowed; patients must be >= 2 weeks post-radiotherapy at time
of registration; a previously irradiated lesion can only be used as a marker lesion
if there is unequivocal evidence of progression demonstrated on serial imaging
studies; patients must have recovered from all toxicities associated with prior
radiotherapy

- Patients must be >= 4 weeks post-major surgery at time of registration; patients must
have recovered from all toxicities associated with prior surgery

- ECOG performance status of 0 or 1

- No history of severe cardiovascular disease (AHA Class III or IV), uncontrolled CHF,
uncontrolled hypertension, or ventricular dysrhythmias

- Patients with previously resected and irradiated CNS metastases with evidence of
stable disease are eligible

- Patients with a history of prior malignancy are eligible provided they were treated
with curative intent and have been disease free for >= 5 years; curatively treated
basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix
must have been treated with curative intent; patients with clinically unsuspected
organ confined prostate cancer found at the time of cystoprostatectomy are eligible

- Creatinine < 1.5 mg/dL

- Granulocytes >= 1500/mm^3

- Platelets >= 100,000/mm^3

- AST =< 2.5 x institutional upper limit of normal

- Bilirubin < 1.5 mg/dl

- No active unresolved infection requiring parenteral antibiotics < 7 days prior to
study entry

- Patients must not have a swallowing dysfunction which would prevent the ingesting of
pills

- Patients must not have any evidence of bleeding diathesis

- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation
(i.e. low dose warfarin) of venous or arterial access devices is allowed provided
that the requirements for PT, INR or PTT are met

- Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs
(phenytoin, carbamazepine, and phenobarbital), rifampin, or St. John's Wort

- Women of childbearing potential must not be pregnant (as proven by a negative
pregnancy test within 14 days prior to registration) or breast feeding because the
effects of this treatment on the fetus and breast-fed infants is unknown

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Kaplan-Meier Estimate of Progression-free Survival at 4 Months

Outcome Description:

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive and progression-free at 4 months. Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.

Outcome Time Frame:

Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.

Safety Issue:

No

Principal Investigator

Robert Dreicer

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02975

NCT ID:

NCT00112905

Start Date:

October 2005

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Bladder
  • Distal Urethral Cancer
  • Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Proximal Urethral Cancer
  • Recurrent Bladder Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Urethral Cancer
  • Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Squamous Cell Carcinoma of the Bladder
  • Stage III Bladder Cancer
  • Stage IV Bladder Cancer
  • Transitional Cell Carcinoma of the Bladder
  • Urethral Cancer Associated With Invasive Bladder Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Carcinoma, Transitional Cell
  • Urethral Neoplasms
  • Kidney Neoplasms
  • Ureteral Neoplasms

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215