Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

• Status: Completed
• Trial end date: 2013-06-27
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Northwestern University
• Treatments: Everolimus; Niacinamide; Sirolimus; Sorafenib

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.