Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

NCT01008917 | Completed Phase 1 DMC

• 1 other identifier: CC# 09455
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; HCC; Liver cancer; Hepatoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  up to 14 months after initial dose

Secondary Outcomes (4)

• Determine safety/toxicity profile of temsirolimus in combination with sorafenib

  Treatment Period up to 22 cycles estimated to be up to 88 weeks

• Describe pharmacokinetics of temsirolimus alone in the cohort of 6 subjects treated at MTD

  Three cycles of treatment estimated to be 12 weeks

• Describe pharmacokinetics of temsirolimus in combination with sorafenib in the cohort of 6 subjects treated at MTD

  Three cycles of treatment estimated to be 12 weeks

• Incidence of progression-free survival, overall survival, and disease control rate

  4 weeks (± 5 days) after removal from study or until death, whichever occurs first

Study Arms (1)

single treatment-non randomized study

EXPERIMENTAL

Phase I study is to test the safety of the combination of sorafenib with temsirolimus at different dose levels

Drug: sorafenib with temsirolimus

Interventions

sorafenib with temsirolimus DRUG

Weekly intravenous temsirolimus with daily oral sorafenib

Also known as: Torisel, Nexavar

single treatment-non randomized study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Northwestern University: collaborator

Study Sites (2)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Sorafenib; temsirolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robin K Kelley, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Alan P Venook, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 6, 2009
• Study Start: November 17, 2009
• Primary Completion: September 12, 2012
• Study Completion: June 27, 2013
• Last Updated: May 9, 2019

Record last verified: 2019-05

Locations

US (2)