Temsirolimus as Second-line Therapy in HCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01567930
Recruitment Status : Unknown
Verified March 2012 by University of Tennessee Cancer Institute.
Recruitment status was:  Recruiting
First Posted : March 30, 2012
Last Update Posted : December 17, 2012
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
University of Tennessee Cancer Institute

Brief Summary:
The purpose of this study is to evaluate the activity of temsirolimus in patients who have advanced hepatocellular carcinoma (HCC) and have been treated with one previous chemotherapy or biologic therapy like sorafenib, but have experienced disease progression or intolerance to that therapy.

Condition or disease Intervention/treatment Phase
Unresectable or Metastatic Hepatocellular Carcinoma Drug: Temsirolimus Phase 2

Detailed Description:

Currently, no standard therapy exists for patients who progress on sorafenib. mTOR signaling is often up-regulated in HCC promoting cell growth and survival. This process is inhibited by rapamycin, a specific inhibitor of mTOR. Temsirolimus, a rapamycin analog, may delay tumor progression by inhibiting mTOR in HCC.Intervention: Temsirolimus IV

Eligible patients will receive temsirolimus IV on days 1,8,15 every 21 days. Treatment will continue till disease progression or untolerable side effects

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Temsirolimus as Second-line Therapy in Patients With Advanced, Unresectable Hepatocellular Carcinoma
Study Start Date : February 2010
Estimated Primary Completion Date : December 2012
Estimated Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Temsirolimus
    Intervention: Temsirolimus IV Eligible patients will receive temsirolimus IV on days 1,8,15 every 21 days. Treatment will continue till disease progression or untolerable side effects
    Other Name: Torisel

Primary Outcome Measures :
  1. Disease Progression
    The primary outcome measure is to determine the proportion of patients who are progression free at 3 months.

Secondary Outcome Measures :
  1. Response rate
    Response rate, clinical benefit rate (complete + partial response + stable disease > 12 weeks) and overall survival with temsirolimus

  2. Safety and tolerability
    Number and frequency of adverse events and serious adverse events will be monitored.

  3. Biochemical response
    Biochemical response (>50% decline in AFP levels from baseline) with temsirolimus

  4. Pharmacokinetics
    Pharmacokinetics will be assessed: AUC pre-dose, 1, 3, 24,48, 72 and 162 hours post dose.

  5. Circulating tumor cells levels
    Feasibility and utility of circulating tumor cells in this patient population

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have advanced unresectable or metastatic hepatocellular carcinoma (HCC). Prior diagnosis of HCC could have been established histologically or based on one of the following criteria:

    • Liver mass > 2cm: Characteristic enhancement on at least one imaging technique(triphasic CT scan, MRI, or contrast enhanced ultrasound) or AFP > 200 ng/ml.
    • Liver mass between 1 and 2 cm: Characteristic enhancement on two imaging techniques.Diagnosis of HCC must have been confirmed by biopsy if non-characteristic enhancement on imaging.
  2. All patients must have received exactly one prior systemic therapy (cytotoxic chemotherapy or targeted therapies) and must not be eligible for further locoregional treatment modalities.
  3. All patients must have measurable disease per RECIST criteria.
  4. Patients with previous locoregional therapies, including but not limited to radio-frequency ablation, cryoablation, percutaneous ethanol injection, chemo-embolization, hepatic artery embolization, and hepatic artery infused FUDR, stereotactic radiotherapy are eligible provided they have documented progression of their disease or have measurable extrahepatic disease.
  5. Patients must have an ECOG performance status of 0 - 2 (see Appendix B).
  6. Patients must be greater than or equal to 18 years of age.
  7. Patients with Child-Pugh class A (score of 5-6) or class B (score of 7-9) are eligible.
  8. Patients must have adequate organ function as defined by:

    • AST, ALT and Alkaline phosphatase ≤ 5x upper limit of normal (ULN)
    • Total Bilirubin < 2 mg/dl.
    • Creatinine clearance ≥ 15ml/min & patients must not be dialysis dependent.
  9. Patients must have adequate bone marrow function as defined by:

    • Leukocytes ≥ 2000 / mm3 or absolute neutrophil count (ANC) ≥ 1000 / mm3
    • Platelet count ≥ 75000 / mm3
  10. Pregnant and nursing women will be excluded from this study. All patients of reproductive potential must agree to use adequate birth control measures to be eligible for study enrollment.
  11. Prior palliative radiotherapy is permissible provided it has been completed at least 2 weeks prior to study entry and the patient has recovered from any radiation-related side effects.
  12. Patients must not be receiving any other investigational agents or other anti-cancer therapies. At least 28 days must have elapsed since completion of previous systemic therapy prior to study entry and the patient should have recovered from all toxicities related to prior therapy.
  13. Patients must not have a history of other malignancies that are active and require therapy (other than non-melanoma skin cancers).

Exclusion Criteria:

  1. Patients with prior treatment with any mTOR inhibitor are not eligible.
  2. Patients with a history of an 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 are not eligible.
  3. Patients taking cytochrome P450 enzyme-inducers or inhibitors are not eligible.
  4. Patients with a known history of HIV infection are not eligible.
  5. Patients with uncontrolled hyperlipidemia or hypercholesterolemia are not eligible (fasting serum cholesterol > 350 mg/dL or fasting serum triglycerides > 400 mg/dL).
  6. Patients with a known history or clinical evidence of CNS metastases are not eligible.
  7. Patients who, in the best judgment of the investigator, will not be able to comply with the requirements of the protocol are not eligible.
  8. Patients with Child-Pugh class C liver disease are not eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01567930

Contact: Steve West, BS, CCRP 901.226.1493

United States, Tennessee
Boston Baskin Cancer Foundation Recruiting
Memphis, Tennessee, United States, 38120
Sponsors and Collaborators
University of Tennessee Cancer Institute
Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: Jasgit Sachdev, MD University of Tennessee Cancer Institute

Responsible Party: University of Tennessee Cancer Institute Identifier: NCT01567930     History of Changes
Other Study ID Numbers: 3066K1‐2247
First Posted: March 30, 2012    Key Record Dates
Last Update Posted: December 17, 2012
Last Verified: March 2012

Keywords provided by University of Tennessee Cancer Institute:
Advanced hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents