Know Cancer

or
forgot password

Single Agent Sorafenib in Advanced Solid Tumors: Phase II Evaluation of Dose Re-Escalation Following a Dose Reduction (IST000375)


Phase 2
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Single Agent Sorafenib in Advanced Solid Tumors: Phase II Evaluation of Dose Re-Escalation Following a Dose Reduction (IST000375)


OBJECTIVES:

Primary

- To evaluate the feasibility of re-escalating the dose of sorafenib tosylate in patients
with advanced malignant solid tumors who initially required a dose reduction for
toxicity, and dose escalation in those patients who are able to tolerate the initial
dose.

Secondary

- To evaluate the efficacy of this drug in these patients who are able to tolerate a dose
escalation initially or after a dose reduction compared to those who are unable to
tolerate a dose escalation.

Tertiary

- To evaluate the percentage and demographic characteristics of patients who are able to
tolerate 2 dose escalations without a dose reduction.

OUTLINE: This is a dose-finding study.

- Course 1: Patients receive oral sorafenib tosylate twice daily at dose level 0 on weeks
1-4.

- Course 2: Patients experiencing no dose-limiting or intolerable toxicities receive oral
sorafenib tosylate at dose level +1 twice daily on weeks 5-8; while patients
experiencing dose-limiting or intolerable toxicities receive oral sorafenib tosylate at
dose level -1 once daily on weeks 5-8.

- Course 3: Depending on whether or not patients are experiencing dose-limiting or
intolerable toxicities, they are escalated to dose level 0 or dose level +2 (patients
in both dose levels receive oral sorafenib tosylate twice daily) in weeks 9-12, or
de-escalated to dose level 0 or dose level -2 (patients in dose level -2 receives oral
sorafenib tosylate once every other day) in weeks 9-12.

- Maintenance therapy: Patients receive oral sorafenib tosylate at the dose level*
attained at the end of course 3. Treatment continues in the absence of unacceptable
toxicity.

NOTE: *Dose level de-escalation for toxicity or dose re-escalation after a toxicity-related
dose reduction allowed to a maximum level of the initial dose level of the maintenance
therapy.

After completion of study therapy, patients are followed for up to 1 year.

Inclusion Criteria


Inclusion Criteria

- Histologically or cytologically confirmed metastatic or unresectable solid tumor for
which standard curative or palliative measures do not exist or are no longer
effective or solid tumor for which sorafenib is considered acceptable therapy

- Age > 18 years old

- Zubrod Performance Status 0 - 2

- Measurable or non-measurable disease.

- Adequate bone marrow, liver and renal function

- Any number of prior chemotherapy regimens are allowed.

- Any prior chemotherapy, immunotherapy or targeted therapy must have been completed at
least 2 weeks prior to start of this protocol and all side effects resolved to grade
1 or less. Any prior radiation must have been completed at least 2 weeks prior to
start of therapy.

- Women of childbearing potential must have a negative pregnancy test performed within
7 days prior to the start of treatment

- Women of childbearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation. Men should use
adequate birth control for at least three months after the last administration of
sorafenib.

- Ability to understand and the willingness to sign a written informed consent.

- INR < 1.5 or a PT/PTT within normal limits.

Exclusion Criteria

- Prior therapy with sorafenib or sunitinib.

- Cardiac disease: Congestive heart failure > class II NYHA.

- Symptomatic or uncontrolled brain metastasis.

- No component of squamous carcinoma can be present in any patient with non-small cell
lung cancer

- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

- Known HIV infection or chronic Hepatitis B or C.

- Active clinically serious infection > CTCAE Grade 2.

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of
study drug.

- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of
study drug.

- Serious non-healing wound, ulcer, or bone fracture.

- Evidence or history of bleeding diathesis or coagulopathy

- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
dose of study drug.

- Use of St. John's Wort or rifampin

- Known or suspected allergy to sorafenib or any agent given in the course of this
trial.

- Any condition that impairs patient's ability to swallow whole pills.

- Any significant malabsorption problem.

- Therapy with bevacizumab < 3 months prior to first dose of study drug.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Percentage of patients who are able to maintain a re-escalated dose of sorafenib tosylate for 28 days without dose interruption or de-escalation for toxicity

Outcome Time Frame:

At least 3 months

Safety Issue:

Yes

Principal Investigator

Primo N. Lara, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000628775

NCT ID:

NCT00810394

Start Date:

December 2008

Completion Date:

March 2012

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

University of California Davis Cancer CenterSacramento, California  95817