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A Phase II Clinical and Correlative Study of BAY 43-9006 (Sorafenib) IND 69,896 in Sarcoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Metastatic Osteosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Osteosarcoma, Stage I Adult Soft Tissue Sarcoma, Stage II Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

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Trial Information

A Phase II Clinical and Correlative Study of BAY 43-9006 (Sorafenib) IND 69,896 in Sarcoma


PRIMARY OBJECTIVES:

I. To determine if the combined VEGF-R2/PDGFR beta inhibitor BAY 43-9006/ sorafenib can
decrease interstitial fluid pressure (IFP) in soft tissue sarcomas.

II. To investigate the effects of BAY 43-9006/sorafenib on tumor blood flow, circulating
endothelial cells, vascular density and pericyte coverage.

III. To characterize the pharmacokinetics of BAY 43-9006/sorafenib in sarcoma patients.

SECONDARY OBJECTIVES:

I. To describe any preliminary evidence of anti-tumor activity. II. Assess whether there are
any significant relationships between systemic drug exposure and drug-related toxicity or
biological effect.

OUTLINE: This is a multicenter study. Patients are assigned to one of two groups (group 1
closed to accrual as of 5/30/07).

GROUP I (SARCOMAS OF THE EXTREMITY) (CLOSED TO ACCRUAL AS OF 5/30/07): Patients receive oral
sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on
approximately day 15. Once patients recover from surgery (and radiotherapy if indicated),
patients who demonstrate a clinically and pathologically significant response (≥ 25%
reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib
as above for a maximum of 6 months in the absence of disease progression or unacceptable
toxicity and at the discretion of the principal investigator. Biopsy tissue and blood
samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at
baseline and immediately before surgery.

GROUP II (METASTATIC OR INOPERABLE SARCOMAS): Patients receive oral sorafenib twice daily on
days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable
disease may continue sorafenib in the absence of disease progression or unacceptable
toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at
baseline and on days 28 and 56.

In both groups, blood samples are drawn periodically for pharmacological studies.

After completion of study therapy, patients are followed monthly until all study-related
toxicities are resolved and then at the discretion of the investigator.


Inclusion Criteria:



- There are two groups of patients eligible for this study; treatment group 1 consists
of patients with extremity sarcomas other than potentially curable osteosarcoma or
Ewing's sarcoma who are candidates for potentially curative surgery; treatment group
2 consists of patients with metastatic or inoperable sarcoma, for which there is no
known curative or survival prolonging palliative therapy, or failure of these
therapies; patients must have at least one site of measurable disease by radiologic
imaging techniques; patients must have at least one palpable tumor mass with no
overlying viscera which is amenable to biopsy; the tumor mass should be approximately
2 cm or greater in diameter; patients with smaller palpable tumors are eligible if
participation is approved by the treating surgeon after discussion with the study
chairperson

- As of 5/30/07, no subjects will accrue to Treatment Group I

- Life expectancy >= 2 months

- ECOG performance status =< 2

- Pretreatment laboratory data, obtained within 14 days of study entry, must meet the
following criteria:

- ANC >= 1,500/mm^3

- Platelets >= 100,000/mm^3

- SGOT =< 2.5-times the upper limit of normal (ULN)

- SGPT =< 2.5-times ULN

- Total Bilirubin =< ULN

- Serum creatinine =< 1.5-times ULN

- >= 3 weeks since major surgery unrelated to study disease (sarcoma)

- >= 3 weeks since chemotherapy or radiation therapy (6 weeks for nitrosourea or
mitomycin C chemotherapy)

- No prior treatment with sorafenib (BAY 43-9006) or specific inhibitors of MAPK kinase
pathways are permitted; a previously irradiated tumor site cannot be used for
clinical or correlative measurements, although irradiation to sites other than a
measurable site is permitted; there are no limitations on the extent or type of prior
therapy received by the patient other than the time intervals indicated in the above
and demonstrating complete recovery from any adverse effects associated by satisfying
all relevant eligibility criteria

- Patients who are on warfarin anticoagulation are allowed to participate as long as
they are converted to a low molecular weight heparin (e.g. lovenox) from study entry
until at least day 56

- Women of childbearing potential must not be pregnant or lactating; all women of
childbearing potential (age < 50, LMP < 12 months ago) must have a negative serum or
urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to
receiving the study medication; BAY43-9006 has antiproliferative effects, which may
be harmful to the developing fetus or nursing infant

- Fertile males and females must use adequate contraception

- Signed informed consent

Exclusion Criteria:

- Ewing's sarcoma or osteosarcoma that is potentially curable with surgery,
chemotherapy, and/or radiation therapy

- Active brain metastases including evidence of cerebral edema by CT scan or MRI, or
progression from prior imaging study, any requirements for steroids, or
enzyme-inducing anti-convulsant agents, or clinical symptoms of/from brain
metastases; patients with treated and/or stable brain metastasis who are asymptomatic
can be enrolled, if otherwise eligible

- Any uncontrolled serious medical or psychiatric illness; particular note is given to
uncontrolled hypertension (discretion left to investigators) and significant
proteinuria > 1 gm/24 hr (does not require quantitation in absence of clinical
indication)

- Patients receiving other investigational agents

- HIV patients receiving combination anti-retroviral therapy are excluded because of
potential pharmacokinetic interactions

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change in FDG uptake (SUVmax)

Outcome Description:

Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.

Outcome Time Frame:

Baseline to up to 1 month post-treatment

Safety Issue:

No

Principal Investigator

Jeffrey Morgan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03122

NCT ID:

NCT00330421

Start Date:

June 2006

Completion Date:

Related Keywords:

  • Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Metastatic Osteosarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Osteosarcoma
  • Stage I Adult Soft Tissue Sarcoma
  • Stage II Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Osteosarcoma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Sarcoma
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115