Temsirolimus as Second-line Therapy in HCC

A Phase II Study of Temsirolimus as Second-line Therapy in Patients With Advanced, Unresectable Hepatocellular Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Unresectable or Metastatic Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Temsirolimus

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
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Steve West, BS, CCRP; Phone Number: 901.226.1493; Email: steve.west@bmhcc.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Boston Baskin Cancer Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Disease Progression	The primary outcome measure is to determine the proportion of patients who are progression free at 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description
Response rate	Response rate, clinical benefit rate (complete + partial response + stable disease > 12 weeks) and overall survival with temsirolimus
Safety and tolerability	Number and frequency of adverse events and serious adverse events will be monitored.
Biochemical response	Biochemical response (>50% decline in AFP levels from baseline) with temsirolimus
Pharmacokinetics	Pharmacokinetics will be assessed: AUC pre-dose, 1, 3, 24,48, 72 and 162 hours post dose.
Circulating tumor cells levels	Feasibility and utility of circulating tumor cells in this patient population

Collaborators and Investigators

• Sponsor: University of Tennessee Cancer Institute
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Jasgit Sachdev, MD, University of Tennessee Cancer Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: February 1, 2012
• First Submitted That Met QC Criteria: March 28, 2012
• First Posted (Estimate): March 30, 2012

Study Record Updates

• Last Update Posted (Estimate): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 13, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: HCC; Temsirolimus; Advanced hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 3066K1-2247