Temsirolimus + Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

NCT01335074 | Withdrawn Phase 1

• 1 other identifier: MRHCCTS2010
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Sorafenib is the standard therapy for advanced liver cancer but often shows dose-limiting toxicities with the need to reduce the applied dose of the compound. As this limits the overall response rate of the therapy, a combination with temsirolimus, an inhibitor of mTOR signaling, will be investigated regarding safety and tolerability in patients with advanced liver cancer under a reduced dose of sorafenib.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  12 weeks

Secondary Outcomes (1)

• Overall response rate

  12 weeks

Study Arms (1)

Temsirolimus + Sorafenib

EXPERIMENTAL

Drug: Temsirolimus + Sorafenib

Interventions

Temsirolimus + Sorafenib DRUG

200mg bid Sorafenib + 15, 20 or 25 mg Temsirolimus

Temsirolimus + Sorafenib

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years of age
• Patients who have a live expectancy of at least 12 weeks
• Patients with histologically or radiologically and serologically confirmed advanced HCC; documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable
• At least one tumor lesion that can be accurately measured in at least one dimension according to RECIST and which has not been treated with local therapy (TACE, PEI, radiofrequency ablation); CT or MRI scans should be not more than 2 weeks old to be used as baseline scan
• Patients who received sorafenib at 400 mg bid with consecutive dose reduction to 200 mg bid due to intolerance, toxicity or adverse events or patients who are not eligible for full-dose first-line therapy with sorafenib, e.g. due to myocardial ischemia.
• At least a period of 4 weeks prior to baseline scan after completion of a local therapy such as surgery, radiation therapy, hepatic arterial embolization, TACE, PEI, radiofrequency ablation, cryoablation or others
• Patients who have an ECOG PS of 0, 1 or 2 or a Karnofsky Performance Status \> 70 %
• Cirrhotic status of Child-Pugh class A or B; Child-Pugh status should be calculated based on clinical findings and laboratory results during the sorafenib pretreatment period
• No signs of decompensated liver cirrhosis
• White blood cells ≥ 3,000/mm³
• Neutrophils ≥ 1,500/mm³
• Platelets ≥ 100,000/mm³
• Bilirubin ≤ 3x ULN
• AST and ALT ≤ 3x ULN
• Creatinine normal

You may not qualify if:

• Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these with 4 weeks of study entry except for standard sorafenib therapy
• Prior use of systemic investigational agents for HCC
• Previous concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors and any cancer curatively treated \> 3 years prior to entry is permitted
• Chronic treatment with steroids or another immunosuppressive agents
• A known history of HIV seropositivity
• Renal failure requiring hemo- or peritoneal dialysis
• History of cardiac disease: congestive heart failure (NYHA \> 2), active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than b-blockers or digoxin, uncontrolled hypertension; myocardial infarction more than 6 months prior to study entry is permitted
• Comedication with known strong Cyp3A4 inhibitors or Cyp3A4/5 inducers
• Active clinically serious infections (\> grade 2 CTCAE v.3.0)
• Known carcinomatous meningitis or uncontrolled brain disease
• Patients with clinically significant gastrointestinal bleeding with 30 days prior to study entry or on oral anti-vitamin K medication (except low dose coumarin, i.e. INR outside the therapeutic range of 2.0 to 3.0)
• History of organ allograft
• Uncontrolled diabetes
• Impairment of gastrointestinal function of gastrointestinal disease that may significantly alter the absorption of sorafenib (e.g. ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Patients who have not recovered from surgery

Sponsors & Collaborators

• Philipps University Marburg: lead

Study Sites (1)

University Hospital Giessen and Marburg

Marburg, 35043, Germany

Location

Related Links

• Related Info

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

Study Officials

• Patrick Michl, MD

  Dept. of Gastroenterology

  PRINCIPAL INVESTIGATOR

• Matthias Ocker, MD

  Inst. for Surgical Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 12, 2011
• First Posted: April 13, 2011
• Study Start: April 1, 2011
• Primary Completion: December 1, 2013
• Last Updated: November 15, 2016

Record last verified: 2011-04

Locations

DE (1)