Vicus Therapeutics Announces Initiation of Phase 2 Trial to Evaluate VT-122 in Patients with Liver Cancer Receiving Nexavar

MORRISTOWN, N.J., Dec. 27, 2010 /PRNewswire/ -- Vicus Therapeutics, LLC, today announced the initiation of a Phase 2 trial evaluating VT-122, a novel investigational combination of etodolac and propranolol, and Nexavar® (sorafenib) tablets, as a potential new treatment option for patients with advanced liver cancer (hepatocellular carcinoma), systemic inflammation and cachexia.  

The randomized, open label, multi-center Phase 2 study will evaluate whether VT-122 in combination with Nexavar increases "Clinical Benefit Response," which is a composite measurement of pain, performance status, and lean body mass, as compared to Nexavar alone.  The secondary efficacy endpoints of this study are cancer and cachexia specific symptoms, duration of Nexavar therapy and overall survival.

The study will be conducted under Vicus' US IND and is expected to enroll 80 patients with advanced liver cancer, systemic inflammation and cachexia at multiple sites in the United States.  Enrollment into this study is expected to be completed by the end of 2011. For more information about enrolling in the study, please visit www.clinicaltrial.gov.

Vicus Therapeutics, LLC, Bayer HealthCare Pharmaceuticals, Inc. and Onyx Pharmaceuticals, Inc. have entered into an agreement pursuant to which Bayer and Onyx have agreed to support the study. The terms of the agreement are confidential.

About Cancer-induced Systemic Inflammation and Cachexia

The most common trajectory of the cancer patient is local progression, development of metastases, cancer-induced systemic inflammation and the associated symptom cluster of the anorexia-cachexia syndrome.  The anorexia-cachexia symptom cluster includes cachexia (anorexia, weight loss and muscle wasting), fatigue, weakness, pain, dyspnea, nausea, malaise, anxiety, depression and poor performance status.(1,2)  This symptom cluster is  further associated with poor tolerance, adherence and response to anti-cancer therapy, disease progression and reduced life expectancy.(1,2)

About Hepatocellular Carcinoma

Hepatocellular carcinoma is the most common form of liver cancer and is responsible for about 90 percent of the primary malignant liver tumors in adults.  Liver cancer is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally.  

About VT-122

VT-122 is a novel investigational combination of etodolac and propranolol that targets pathways associated with cancer-induced systemic inflammation, a suspected cause of cancer cachexia.(1,2) VT-122 has demonstrated the ability to increase lean body mass (muscle) and lower other markers of systemic inflammation in a Phase 2 trial of patients with advanced lung cancer.(3) Preclinical and clinical studies show that propranolol and etodolac, when used individually, attenuate systemic inflammation, hypermetabolism, and weight loss.(4,5,6)  Furthermore, non-clinical studies show that this combination acts synergistically to attenuate systemic inflammation, activate cellular immunity, reduce metastasis, and increase animal survival.(7)

About Nexavar

Nexavar is approved in the U.S. for the treatment of patients with unresectable liver cancer and for the treatment of patients with advanced kidney cancer.  Nexavar inhibits both the tumor cell and tumor vasculature.  In preclinical studies, Nexavar has been shown to inhibit members of two classes of kinases thought to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth.  These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.  

Nexavar is currently approved in 99 countries.  

Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators.

Important Safety Considerations For Patients Taking Nexavar

NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and Female patients should also be advised against breast-feeding while receiving Nexavar.

Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction.  Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar.

Uncommon but serious adverse reactions including keratoacanthomas/squamous cell cancer of the skin and Stevens - Johnson Syndrome have been reported in clinical trials

An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar.

Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required.

Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief.  In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered.

Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures.

Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar.  Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers.  Concomitant use of carboplatin and paclitaxel with sorafenib resulted in an increase in paclitaxel exposure and an increase in Nexavar exposure.  Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%),and  nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%.

For information about Nexavar including U.S. Nexavar prescribing information, visit www.nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).

About Vicus Therapeutics, LLC

Vicus Therapeutics is a biopharmaceutical company dedicated to bringing breakthrough therapies to patients with cancer.  Vicus' lead investigational therapy, VT-122, is a combination of etodolac and propranolol.  VT-122 showed positive results in a Phase 2 clinical trial of lung cancer patients and is currently being evaluated in a Phase 2 clinical trial of liver cancer patients receiving Nexavar (sorafenib). For additional information about Vicus, please visit the company's website at www.vicustherapeutics.com.

(1) N. MacDonald. Cancer cachexia and targeting chronic inflammation: a unified approach to cancer treatment and palliative/supportive care.  J.Support.Oncol. 2007 Apr;5(4):157-62.

(2) D.C. McMillan. Systemic inflammation, nutritional status and survival in patients with cancer.  Curr Opin Clin Nutr Metab Care. 2009 May;12(3):223-6.

(3) G.S. Bhattacharyya et al.  Phase II study evaluating safety and efficacy of coadministering propranolol and etodolac for treating cancer cachexia.  J Clin Oncol. 28, 2010 (suppl; abstr e18059).

(4) M.J.  Muller. Hypermetabolism in clinically stable patients with liver cirrhosis. Am J Clin Nutr.  69: 1194– 1201, 1999.

(5) A. Gambardella et al. Intralipid infusion combined with propranolol administration has favorable metabolic effects in elderly malnourished cancer patients. Metabolism. 1999 Mar; 48(3):291-7.

(6) D.C. McMillan et al. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer. 1999. 79(3-4): p. 495-500.

(7) A. Glasner et al. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol. 2010. 184(5): p. 2449-57.

SOURCE Vicus Therapeutics, LLC