Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

NCT01687673 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 124511NCI-2012-02021
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase II trial is being developed following the completion of a Phase I study of the combination of temsirolimus and sorafenib in 25 first-line therapy patients with advanced hepatocellular carcinoma (December 2009 through April 2012). The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of temsirolimus is 10 mg IV weekly plus sorafenib 200 mg (oral, twice daily).

Conditions

Hepatocellular Carcinoma

Keywords

Advanced HCC; Temsirolimus; TORISEL; Sorafenib

Outcome Measures

Primary Outcomes (1)

• Median Time to Progression (TTP)

  Median TTP will be calculated in months from date of first dose of protocol therapy to date of removal from study for progression, where progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of the target lesions (SLD), taking as reference the smallest sum of the SLD recorded since the treatment started and minimum 5 millimeter (mm) increase over the nadir, or the appearance of one or more new lesions for target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions . Kaplan-Meier methods will be used to summarize the primary endpoint

  24 months

Secondary Outcomes (8)

• Response Rate (RR)

  24 months

• Median Progression Free Survival (PFS)

  24 months

• Median Overall Survival (OS)

  60 months

• Time to Treatment Failure (TTF)

  24 months

• Number of Patients With a Demonstrated Alpha-fetoprotein (AFP) Response

  24 months

Study Arms (1)

Treatment

EXPERIMENTAL

Combination temsirolimus plus sorafenib

Drug: Temsirolimus; Drug: Sorafenib:

Interventions

Temsirolimus DRUG

10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment.

Treatment

Sorafenib: DRUG

200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.

Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically diagnosed American Joint Committee on Cancer (AJCC) stage II, III, or IV hepatocellular carcinoma (HCC) not eligible for curative resection, transplantation, or ablative therapies
• Radiographically measurable disease by RECIST version 1.1 in at least one site not previously treated with chemoembolization, radioembolization, or other local ablative procedures (i.e. must have at least one measurable target lesion, either within the liver or in a measurable metastatic site); a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a Radiologist, is acceptable
• No prior systemic cytotoxic chemotherapy or targeted therapy (including sorafenib) for HCC
• Prior chemoembolization, local ablative therapies, or hepatic resection permitted if completed ≥ 4 weeks prior to study enrollment if patient has recovered with ≤ grade 1 toxicity and if measurable disease (criterion 2) 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.
• Age ≥ 18 years.
• Child-Pugh score of A or B with ≤ 7 points and meeting laboratory eligibility for all parameters
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than 3 months
• Treatment with appropriate antiviral therapy for patients with active hepatitis B Virus (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 ≤ 150 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 7.5% (with or without the use of anti-diabetic medications)
• Adequate baseline organ and marrow function as defined below

You may not qualify if:

• Mixed tumor histology or fibrolamellar variant tumors are excluded.
• Prior systemic or antiangiogenic therapy for HCC (including thalidomide, sorafenib, sunitinib, or bevacizumab). Prior systemic therapy for other diagnoses is permitted if greater than 6 months have elapsed since last dose, any prior toxicity has recovered to ≤ grade 1 by CTCAE v4.0, and treatment was not discontinued for toxicity.
• 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 ineligible due to risk of pharmacokinetic interactions between anti-retroviral therapy and the study drugs, as well as potential for significant immunosuppression and serious infections with mTOR inhibition.
• Patients who have undergone liver transplantation are excluded.
• Uncontrolled hypertension (\> 150/90 mmHg).
• Uncontrolled hyperlipidemia (total cholesterol \> 350 or triglycerides \> 300).
• 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.
• Major surgical procedure less than 4 weeks from start of protocol treatment.
• 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. (Patients with history of malignancy are not considered to have a "currently active" malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse.)

Sponsors & Collaborators

• University of California, San Francisco: lead
• Robert H. Lurie Cancer Center: collaborator
• Pfizer: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

temsirolimus; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver 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

Results Point of Contact

• Title: Dr. R. Katie Kelley, MD
• Organization: University of California, San Francisco

Katie.Kelley@ucsf.edu

(415) 353-9888

Study Officials

• Kate Kelley, MD

  University of California, San Francisco

  STUDY CHAIR

• Kate Kelley, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: September 19, 2012
• Study Start: October 5, 2012
• Primary Completion: April 26, 2016
• Study Completion: January 9, 2020
• Last Updated: December 7, 2020
• Results First Posted: December 7, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)