Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Northwestern University
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01008917
First received: October 30, 2009
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

This is a Phase I study, which means that the goal is to see if the combination of Temsirolimus and Sorafenib is safe in patients with Hepatocellular Carcinoma. Sorafenib is a standard treatment for Hepatocellular Carcinoma. Temsirolimus is used to treat cancer in the kidneys. It is hoped that the addition of Temsirolimus will make Sorafenib more effective against Advanced Hepatocellular Carcinoma, however this can not be guaranteed. The addition of Temsirolimus to Sorafenib is not an FDA approved treatment for Advanced Hepatocellular cancer.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: sorafenib with temsirolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: up to 14 months after initial dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine safety/toxicity profile of temsirolimus in combination with sorafenib [ Time Frame: Treatment Period up to 22 cycles estimated to be up to 88 weeks ] [ Designated as safety issue: Yes ]
    each cycle is 4 weeks long

  • Describe pharmacokinetics of temsirolimus alone in the cohort of 6 subjects treated at MTD [ Time Frame: Three cycles of treatment estimated to be 12 weeks ] [ Designated as safety issue: No ]
    each cycle is 4 weeks long

  • Describe pharmacokinetics of temsirolimus in combination with sorafenib in the cohort of 6 subjects treated at MTD [ Time Frame: Three cycles of treatment estimated to be 12 weeks ] [ Designated as safety issue: No ]
    each cycle is 4 weeks long

  • Incidence of progression-free survival, overall survival, and disease control rate [ Time Frame: 4 weeks (± 5 days) after removal from study or until death, whichever occurs first ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: November 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: single treatment-non randomized study
Phase I study is to test the safety of the combination of sorafenib with temsirolimus at different dose levels
Drug: sorafenib with temsirolimus
Weekly intravenous temsirolimus with daily oral sorafenib
Other Names:
  • Torisel
  • Nexavar

  Show Detailed Description

  Eligibility

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

Inclusion Criteria

  • Histologically or clinically* diagnosed AJCC stage III or IV HCC not amenable to curative resection and with no prior systemic cytotoxic or molecularly-targeted therapies. *Clinical diagnosis is acceptable if tumor meets radiographic criteria.
  • Age ≥ 18 years.
  • Child-Pugh score A or score of B with 7 points only and bilirubin ≤ 2 mg/dL.
  • ECOG performance status ≤ 2.
  • Radiographically measurable disease in at least one site not previously treated with chemoembolization, radioembolization, or other local ablative procedures.
  • Prior chemoembolization, local ablative therapies, or hepatic resection permitted if completed ≥ 6 weeks prior to study enrollment and if criterion 6 is present.
  • Prior radiation for bone or brain metastases is permitted if patient is now asymptomatic and has completed all radiation and steroid therapy (if applicable) for brain or bone metastases ≥ 2 weeks prior to study enrollment.
  • Treatment with appropriate antiviral therapy for patients with active HBV infection is required.
  • Treatment for clinically-significant hyperglycemia, hyperlipidemia, or hypertension that develops on study is required.
  • Baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic < 140 mm Hg, diastolic < 90 mm Hg).
  • Baseline cholesterol must be < 350 mg/dL and triglycerides < 300 mg/dL (with or without the use of antihyperlipidemic medications).
  • Baseline fasting blood glucose must be ≤ 140 mg/dL and hemoglobin A1c less than 7% (with or without the use of anti-diabetic medications).
  • Adequate baseline organ and marrow function as defined below:
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 75,000/mcL
  • Hemoglobin ≥ 8.5 g/dL
  • Total bilirubin ≤ 2 mg/dL or ≤ 1.5 times ULN
  • AST(SGOT)/ALT(SGPT) ≤ 5 times ULN
  • INR ≤ 1.5 times ULN
  • Albumin ≥ 2.8 g/dL
  • Creatinine ≤ 1.5 times ULN
  • Able to tolerate oral therapy.
  • Ability to give written informed consent and willingness to comply with the requirements of the protocol.
  • Effective means of contraception are required in fertile, sexually-active patients.

Exclusion Criteria

  • Mixed tumor histology or fibrolamellar variant tumors are excluded.
  • Prior antiangiogenic therapy (including thalidomide, sorafenib, sunitinib, or bevacizumab).
  • Prior treatment with mTOR inhibitor or other molecularly targeted therapy.
  • Prior systemic cytotoxic therapies for HCC (chemoembolization is permitted if inclusion criteria are met).
  • Treatment with other investigational agents.
  • Immunosuppressive medications including systemic corticosteroids unless used for adrenal replacement, appetite stimulation, acute therapy for asthma or bronchitis exacerbation (≤ 2 weeks), or antiemesis.
  • Patients with known HIV infection are excluded.
  • Patients who have undergone liver transplantation are excluded.
  • Symptomatic brain or bone metastases; prior radiation and/or steroid therapy for brain or bone metastases (if applicable) must be completed ≥ 2 weeks prior to study enrollment.
  • History of seizure disorder requiring antiepileptic medication or brain metastases with seizures.
  • Serious non-healing wound, ulcer, bone fracture, or abscess.
  • Patients requiring chronic anticoagulation with warfarin are excluded. Patients treated with low molecular weight heparin or unfractionated heparin are eligible if on a stable dose without evidence of clinically significant bleeding for at least 2 weeks prior to enrollment.
  • Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.
  • Uncontrolled intercurrent illness.
  • No required concomitant medications with potential for significant interaction with study drugs.
  • Any other condition that compromises compliance with the objectives and procedures of this protocol, as judged by the Study Chair, is also grounds for exclusion.
  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: NCT01008917

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
University of California, San Francisco
Northwestern University
Investigators
Principal Investigator: Robin K Kelley, MD University of California, San Francisco
Principal Investigator: Alan P Venook, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01008917     History of Changes
Obsolete Identifiers: NCT01013519
Other Study ID Numbers: CC# 09455
Study First Received: October 30, 2009
Last Updated: October 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Hepatocellular carcinoma
HCC
Liver cancer
Hepatoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014