Sorafenib and Temsirolimus in Treating Patients With Recurrent Glioblastoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2013 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00329719
First received: May 23, 2006
Last updated: May 29, 2015
Last verified: June 2013
  Purpose

This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma. Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib and temsirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sorafenib together with temsirolimus may kill more tumor cells.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: sorafenib tosylate
Drug: temsirolimus
Procedure: conventional surgery
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Sorafenib and CCI-779 in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

    The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation.

    If more than 41 evaluable patients are accrued in group 1 or group 3, the additional patients will not be used to evaluate the decision rule for that group or otherwise used in any decision-making processes. However, they will be included in the final point and confidence interval estimates for that group.

    The 'success' probability, i.e., 6-month progression-free survival percentage, for each of group 1 and group 3 will be estimated as the number of evaluable patients still alive at 6 months divided by the total number of evaluable patients followed for at least 6 months. Ninety-five percent confidence intervals for the 'success' probability will be calculated according to the approach of Duffy and Santner.

    Progression is defined as a 25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From start of study registration to death due to any cause or until last follow-up, up to 5 years ] [ Designated as safety issue: No ]
    The overall survival distribution will be estimated using the method of Kaplan-Meier.

  • Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients in each response category will be summarized and 90% confidence intervals calculated assuming that the incidence of response is binomially distributed.

  • Progression-free Survival [ Time Frame: Time from study registration to date of disease progression or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curves will be used to estimate progression-time distributions.


Enrollment: 115
Study Start Date: March 2006
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I, Arm A

Phase I, Arm A, Dose Escalation

Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Experimental: Phase II, Arm B

Phase II, Arm B, Group I (patients not undergoing surgery)

Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).

Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Experimental: Phase II, Arm C

Phase II, Arm C, Group II (patients undergoing surgery)

Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).

Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Procedure: conventional surgery
Undergo surgery
Other Name: surgery, conventional
Experimental: Phase II, Arm D

Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)

Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).

Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Central pathology review submission prior to registration to confirm eligibility. It should be initiated as soon after surgery as possible.
  • ≤2 prior systemic chemotherapy regimens.
  • ≥18 years of age.
  • Histological confirmation of a grade 4 astrocytoma (glioblastoma) or gliosarcoma, at primary diagnosis or recurrence by World Health Organization (WHO) criteria. Central pathology review is mandatory prior to study entry to confirm eligibility.
  • Evidence of tumor progression by Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scan following Radiation Therapy (RT) or following the most recent anti-tumor therapy.
  • Bidimensionally measurable or evaluable disease by MRI or CT scan.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2.
  • ≥12 weeks since the completion of RT.
  • Fixed or decreasing dose of corticosteroids (or no corticosteroids) ≥1 week prior to registration.
  • ≥1 week from minor surgery other than venous line placement and >3 weeks from major surgery.
  • ≥4 weeks from prior cytotoxic chemotherapy (≥6 weeks for nitrosoureas).
  • ≥2 weeks from cytostatic chemotherapy such as tamoxifen, cis-retinoic acid, or thalidomide.
  • The following laboratory values obtained ≤7 days prior to registration:

    • WBC ≥3000/mm3
    • ANC ≥1500/mm3
    • PLT ≥100,000/mm3
    • Hgb ≥10 gm/dL
    • Total bilirubin ≤1.5 x ULN
    • SGOT (AST) ≤2.5 x ULN
    • Creatinine ≤2.0 x ULN
    • Serum cholesterol ≤350 mg/dL
    • Serum triglycerides ≤400 mg/dL
  • Willingness to provide the biologic specimens as required by the protocol. (Please note that the willingness to participate pertains only to the patient and does not factor in the institution's ability to participate in any part of the translational component.)

Exclusion Criteria:

  • Prior intratumoral chemotherapy (e.g. Gliadel or IL13-PE38QQR), stereotactic radiosurgery or interstitial brachytherapy unless there is a separate lesion on MRI which is not part of the previous treatment field or there is proof of recurrent disease based on biopsy, MRI spectroscopy, or Positron Emission Tomography (PET) scan.
  • Prior CCI-779, sorafenib, or other agents specifically targeting mTOR or raf. Patients receiving prior agents inhibiting VEGF or VEGFR (prior anti-VEGF group) are eligible but: 1) must be at least four weeks from last treatment with the agent(s); and 2) must have recovered from any clinically relevant toxicities attributable to this agent(s).
  • Evidence of bleeding diathesis or coagulopathy.

    • Note: Patients on prophylactic anticoagulation therapy (e.g., low-dose warfarin) are eligible provided their coagulation parameter levels are as follows: prothrombin time (INR; International Normalized Ratio of prothrombin time) <1.1 x institutional upper limit of normal.
    • Note: Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met: a) the patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, and b) the patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
  • INR >1.5 (unless the patient is on full dose warfarin).
  • Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, fosphenytoin, carbamazepine, phenobarbital, or primidone) or any other potent CYP3A4 inducer such as rifampin or St. John's wort.
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills.
  • Hypertension with systolic blood pressure of >140 mmHg or diastolic pressure >90 mmHg. However, patients with well-controlled hypertension are eligible.
  • Uncontrolled infection.
  • Any of the following because temsirolimus and sorafenib are investigational agents whose genotoxic effects on the developing fetus and newborn are unknown:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Known hypersensitivity to any of the components of temsirolimus or sorafenib.
  • Other active malignancy.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with temsirolimus and sorafenib.
  • Receiving any investigational agents other than temsirolimus and sorafenib.
  • Significant intratumoral, intracerebral, or subarachnoid hemorrhage on baseline MRI or CT, or other history of significant intratumoral, intracerebral, or subarachnoid hemorrhage.
  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: NCT00329719

  Show 176 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Kurt Jaeckle North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00329719     History of Changes
Other Study ID Numbers: NCI-2009-00652, N0572, CDR0000472240, NCCTG-N0572, U10CA025224
Study First Received: May 23, 2006
Results First Received: June 2, 2014
Last Updated: May 29, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Everolimus
Sirolimus
Sorafenib
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015