Clinical Trials News

Antioxidants Offer Pain Relief In Patients With Chronic Pancreatitis

2009-01-06T13:26:00.000-08:00

Antioxidant supplementation was found to be effective in relieving pain and reducing levels of oxidative stress in patients with chronic pancreatitis (CP), reports a new study in Gastroenterology. CP is a progressive inflammatory disease of the pancreas in which patients experience abdominal pain (in early stage) and diabetes and maldigestion (in late stage). Pain is the major problem in 90 percent of patients with CP and currently, there is no effective medical therapy for pain relief. Gastroenterology is the official journal of the American Gastroenterological Association (AGA) Institute.

In this placebo-controlled, double blind trial, 127 patients, ages 30.5+/-10.5, were assigned to placebo or antioxidant groups. After six months, the reduction in the number of painful days/month was significantly higher in the antioxidant group, compared with the placebo group (7.4±6.8 versus 3.2±4, respectively). The reduction in the number of analgesic tablets/month was also higher in the antioxidant group (10.5±11.8 versus 4.4±5.8, respectively). Furthermore, 32 percent and 13 percent of patients became pain free in the antioxidant and placebo groups, respectively; the beneficial effect of antioxidants on pain relief was noted early at three months.

"Abdominal pain, the predominant symptom in patients with CP, is difficult to treat. The main reason for a largely ineffective medical treatment is that the mechanism of pain in CP is not well understood," said Pramod Kumar Garg, MD, DM, of the All India Institute of Medical Sciences, New Delhi and lead author of the study. "We are encouraged by our findings, as significant improvement was noted with antioxidants in respect to all the parameters of pain in this study. In addition, reduction in pain resulted in fewer man-days lost, thus providing functional employment gain to the patients. The findings should spur further research in this exciting area."

There are two important implications of this study - the fact that measures of oxidative stress were increased initially and decreased subsequently after supplementation with antioxidants suggests that there is a state of heightened free radical mediated injury in CP, and that injury is reversible. Second, with regard to pain management, this trial showed that antioxidant therapy is effective for pain relief in patients with CP. This assumes significance since no effective medical therapy exists for pain relief for such patients.

Pancreatitis is inflammation of the pancreas that usually begins as a sudden attack and is often caused by gallstones, alcohol abuse or genetic mutations. Symptoms of pancreatitis start with a gradual or sudden severe pain in the center part of the upper abdomen going through to the back. Treatment often focuses on the nutritional and metabolic needs of the patient and on relieving pain. Most people with chronic pancreatitis have a good prognosis if they follow their treatment regimen. "Aside from medication, abstaining from alcohol and smoking are most important and key to halt the progression of CP," added Dr. Garg.

What Is The Best Strategy For Treating Helicobacter Pylori?

2008-09-24T12:20:00.000-07:00

The most popular treatment for H pylori is triple therapy but resistance to Clarithromycin is reducing its effectiveness. Courses using four drugs have been known to be more successful but are used less popular because of their side-effects. While, what is the best way for treating H pylori-related diseases.
A research article to be published on 28 June 2008, in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Mr Siok Ching from United Kingdom compared a lansoprazole-based triple versus quadruple therapy for H pylori eradication with emphasis on side effect profile, patient compliance and eradication rate at a rural district general hospital in Wales, United Kingdom.

Overall the treatment of H Pylori using both three drugs and four drugs are still highly effective in rural North Wales (92%), however, almost all (97%) of the patients who managed to complete the course of four tablets got rid of the infection.

Authors feel that treatments with four drugs remain the best option for white Caucasians in rural UK. Patients need educating about the side effects of the drugs and the reasons for treatment so that they can reap the full benefits.

They concluded that one-week triple and quadruple therapies have similar intention-to-treat eradication rates. Certain side effects are more common with quadruple therapy, which can compromise patient compliance. Patient education or modifications to the regimen are alternative options to improve compliance of the quadruple regimen.

The side effects may be reduced by replacing metronidazole with amoxycillin but patients should be better educated about the side effects in order to improve compliance and cure rates.

Is Mirtazapine And Fluoxetine Helpful In Treating Pancreatic Cancer?

2008-09-24T12:17:00.000-07:00

The treatment of pancreatic cancer remains a great challenge. The majority of patients with pancreatic cancer developed major depression. Antidepressant treatment has been accepted as one of the new strategies in cancer adjuvant therapy. However, systemic studies on the treatment of depression in patients with cancer have not been well documented.

A research article published in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Jia Lin evaluated the effectiveness of mirtazapine and fluoxetine on body weight, ingestive behavior, locomotor activity and tumor growth in a pancreatic cancer mouse model in the six-week period trial.

In this study, the researchers observed that mirtazapine had the effectiveness of increasing appetite, partly reversed the rate of weight loss. In addition, the potential effectiveness of weight gain associated with an increase in food intake. However, fluoxetine produced a significant suppression of food intake and promoted weight loss. These effects lasted a long-term. Mirtazapine and fluoxetine didn't affect the pancreatic tumor growth. Mirtazapine had more quickly efficacy on the adaptability to new environment than fluoxetine.

Erbitux(R) Cetuximab ,Phase III Clinical Study In Gastric Cancer Started

2008-07-10T05:35:00.000-07:00

Merck Serono, a division of Merck KGaA, announced that the first patient has been enrolled into its pivotal Phase III gastric cancer clinical study, EXPAND (Erbitux in combination with Xeloda and cisplatin in advanced esophago-gastric cancer). The study will assess the clinical benefit of the targeted cancer therapy

Erbitux® (cetuximab) in combination with cisplatin and capecitabine as a 1st-line treatment for patients with advanced/metastatic gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma. The primary endpoint of the study is progression-free survival.

"The start of the EXPAND study is very exciting because there is a real unmet medical need in this treatment area," said Dr Florian Lordick, National Center for Tumor Diseases University of Heidelberg, Germany, Lead Investigator for the EXPAND study.

Gastric cancer, also known as stomach cancer, is notoriously difficult to treat and is associated with a poor prognosis. In resectable gastric cancer, surgery is potentially curative, but the majority of patients present with late stage disease and are therefore candidates for palliative chemotherapy only.

"Recruitment into this pivotal trial follows three successful Phase II studies in 1st-line gastric cancer. The EXPAND study is another step in the development of Erbitux in this treatment area," said Dr. Wolfgang Wein, Executive Vice President for Merck Serono's Global Oncology Unit. "Combining standard chemotherapy regimens with innovative targeted agents, such as Erbitux, is key to providing more effective cancer treatments and underpins Merck Serono's commitment to oncology."

Erbitux is a monoclonal antibody (MAb) already approved for the treatment of colorectal and head and neck cancers and has also demonstrated as the first targeted therapy to show a significant survival benefit in 1st-line non-small-cell lung cancer in patients across all histological subtypes.1 Like the antibodies circulating as part of the immune system, Erbitux identifies and locks on to a specific target - in this case, the epidermal growth factor receptor (EGFR), which is expressed in certain cancers, including gastric cancer.

Gastric cancer is the second leading cause of cancer death in men and the fourth among women worldwide. Generally, gastric cancer rates are about twice as high in men as in women.2 Each year nearly 930,000 people worldwide are diagnosed with gastric cancer and approximately 700,000 die of the disease.3

EXPAND is a multi-center, open-label, controlled study that will recruit approximately 870 patients at 150 centers in 25 countries worldwide.

Additive Anti-Tumor Activity Of NKTR-102 In Combination With Bevacizumab Highlighted In Positive Preclinical Data Presented At AACR Meeting

2008-04-15T05:41:00.001-07:00

Positive preclinical data was presented by Nektar Therapeutics (Nasdaq: NKTR) this week for its lead oncolytic candidate, NKTR-102 (PEG-irinotecan), which demonstrated enhanced anti-tumor activity in a mouse xenograft model of colorectal cancer when co-administered with bevacizumab. Presented at the American Association for Cancer Research (AACR) Annual Meeting 2008 in San Diego, California, the data also featured the enhanced pharmacokinetic profile and tolerability of NKTR-102, as compared to irinotecan in animal models.

NKTR-102 is a PEGylated form of irinotecan developed using Nektar's innovative small molecule PEGylation technology platform. NKTR-102 is currently in a Phase 2 development program to evaluate its safety and efficacy as a second-line colorectal cancer therapy in combination with cetuximab. Nektar had previously announced its intention to expand the NKTR-102 Phase 2 clinical development program later this year with additional indications.

"NKTR-102 is demonstrating important promise as a solid tumor treatment that could be used in a number of critical cancer care regimens," said Tim Riley, Ph.D., Vice President of PEGylation Research at Nektar. "These data reinforce our confidence in the potential of our small molecule PEGylation technology platform to improve the therapeutic potential of oncolytics that are widely used to treat cancer. We look forward to presenting new data from our clinical trials at additional major oncology conferences this year."

In the preclinical studies presented at AACR, NKTR-102 was co-administered with bevacizumab to evaluate the effects of combination therapy. The combination therapy had an additive effect, inhibiting tumor growth by up to 97% in an irinotecan-resistant mouse xenograft model of colorectal cancer (HT29), which was greater than monotherapy with either NKTR-102 or bevacizumab. NKTR-102 at 46 mg/kg, co-administered with bevacizumab, also resulted in eight partial tumor regressions and one complete tumor regression. This compares to no tumor regressions observed with bevacizumab monotherapy, and two partial regressions and one complete regression with NKTR-102 monotherapy. NKTR-102 alone, and in combination with bevacizumab, was well-tolerated, with minimal weight loss.

NKTR-102 also exhibited superior pharmacokinetics in a repeated dose study in dogs, with a 6-fold increase in exposure (AUC) and a 4-fold lower peak plasma concentration (Cmax) of SN38, the active metabolite of irinotecan, as compared to the equivalent dosing of irinotecan. The lower peak plasma concentration of NKTR-102 was associated with a superior tolerability profile, with less gastrointestinal and hematopoietic toxicity than comparable doses of irinotecan.

In animal models, NKTR-102 had a markedly improved safety and tolerability profile when compared to irinotecan in animal models. Both the incidence and severity of diarrhea and neutropenia were lower in dogs treated with NKTR-102 as compared to irinotecan. Diarrhea and neutropenia are the most common side effects associated with irinotecan treatment, and can limit treatment with the therapy.

Data Presentations

#766: "Enhanced anti-tumor activity of NKTR-102, a novel PEGylated-irinotecan, when administered in combination with bevacizumab in a mouse model of human colorectal tumors"

#5741: "NKTR-102, a novel PEGylated-irinotecan, has an enhanced pharmacokinetic profile with reduced gastrointestinal and hematopoietic toxicity compared to irinotecan with repeat dosing in dogs"

#5742: "NKTR-102, a novel PEGylated-irinotecan, has a superior acute safety, tolerability, and pharmacokinetic profile compared to irinotecan in rats and dogs"

About NKTR-102

Nektar is developing NKTR-102, a PEGylated form of irinotecan, which was invented by Nektar using its world-leading small molecule PEGylation technology platform. The product is currently in Phase 2 clinical development. Irinotecan is an important chemotherapeutic agent used for the treatment of solid tumors, including colorectal and lung cancers. By applying Nektar's small molecule PEGylation technology to irinotecan, NKTR-102 may prove to be a more powerful and tolerable anti-tumor agent. Preclinical studies show that treatment with NKTR-102 results in significant suppression of tumor growth in an irinotecan-resistant mouse colorectal tumor model and in similar models of breast and lung cancer. Administration of NKTR-102 in an animal model also results in a markedly improved time-concentration profile for SN38, the active metabolite of irinotecan, as compared to treatment with irinotecan.

Nektar PEGylation Platform

Nektar PEGylation technology can enhance the properties of therapeutic agents by increasing drug circulation time in the bloodstream, decreasing immunogenicity and dosing frequency, increasing bioavailability and improving drug solubility and stability. It can also be used to modify pharmaceutical agents to preferentially target certain systems within the body. It is a technique in which non-toxic polyethylene glycol (PEG) polymers are attached to therapeutic agents, and it is applicable to most major drug classes, including proteins, peptides, antibody fragments, small molecules, and other drugs.

Nektar PEGylation technology is also used in eight additional approved partnered products in the U.S. or Europe today, including Roche's PEGASYS(R) for hepatitis C and Amgen's Neulasta(R) for neutropenia.

About Nektar

Nektar Therapeutics is a biopharmaceutical company that develops and enables differentiated therapeutics with its industry-leading PEGylation and pulmonary drug development technology platforms. Nektar PEGylation and pulmonary technology, expertise, manufacturing capabilities have enabled eight approved products for partners, which include the world's leading pharmaceutical and biotechnology companies. Nektar also develops its own products by applying its PEGylation and pulmonary technology platforms to existing medicines with the objective to enhance performance, such as improving efficacy, safety and compliance.

This press release contains forward-looking statements regarding the potential of NKTR-102 and the company's PEGylation technology platform. These forward-looking statements involve important risks and uncertainties, including but not limited to: (i) preclinical testing and clinical trials for NKTR-102 are long, expensive and uncertain processes, (ii) because the NKTR- 102 product development programs are in the early phases of clinical development, the risk of failure is high and can occur at any stage of development, (iii) the company may fail to obtain regulatory approval of NKTR- 102, (iv) the timing or success of the commencement or conclusion of NKTR-102 clinical trials is subject to a number of uncertainties including but not limited to clinical design, patient enrollment, regulatory requirements and clinical outcomes (v) potential competition from existing approved products (branded or generic) or product candidates under development by other companies could negatively impact the commercial potential of NKTR-102 due to such common industry competitive factors as efficacy and safety profiles, pricing, and reimbursement by third party payers, and (vi) the company's patent applications for NKTR-102 may fail to issue; patents that have issued may not be enforceable; or unanticipated intellectual property licenses from third parties may be required in the future. Other important risks and uncertainties are detailed in the company's reports and other filings with the SEC including its most recent Annual Report on Form 10-K. Actual results could differ materially from the forward-looking statements contained in this press release. The company undertakes no obligation to update forward-looking statements, whether as a result of new information, future events, or otherwise. No information regarding or presented at the scientific meetings referred to above (or contained at the Internet links provided) is intended to be incorporated by reference in this press release.

Drug Combination Reduces Colon Cancer Risk With Reduced Toxic

2008-04-15T05:34:00.000-07:00

Using a combination of a targeted cancer-fighting agent called DFMO and a low dose of an anti-inflammatory drug, UC Irvine researchers have reduced the risk of reoccurring colorectal polyps, an early sign of colon cancer, by as much as 95 percent with fewer toxic side effects.

The study marks a breakthrough in the effort to combat colon cancer, the third leading cause of cancer in men and fourth in women, according to Dr. Frank L. Meyskens Jr., the Daniel G. Aldrich Chair at UC Irvine and director of its Chao Family Comprehensive Cancer Center.

"There is a great hope that we will be able to prevent colon cancer effectively using this method," said Meyskens, who led the clinical trial effort to test this drug combination. He presented his findings at the American Association for Cancer Research annual meeting in San Diego.

In earlier studies, Meyskens had established a safe and well-tolerated dose of DFMO (difluoromethylornithine) that was 1/50 of what would typically be used to treat advanced cancers. By combining this reduced dose of DFMO with a non-steroidal, anti-inflammatory drug called sulindac, researchers believed they could improve treatment and decrease the reoccurrence of potentially cancerous colon polyps with reduced toxic side effects.

DFMO is the basis of the drug eflornithine, which was initially developed as a cancer medication and is no longer manufactured commercially for that purpose. Sulindac is sold commercially as Clinoril and is used to treat arthritis and other inflammatory conditions.

The researchers enrolled 375 patients who had a history of at least one colorectal polyp, or adenoma, within the previous five years. Patients were randomly assigned to either a combination of 500 mg of daily DFMO and 150 mg of sulindac or placebos. Patients were followed for three years, and adenoma recurrence was measured by colonoscopy. Among the results:
Overall risk for recurrent adenoma: 41.1 percent in placebo group to 12.3 percent in treated patients, a 79 percent reduction

Risk for recurrent advanced adenomas: 8.5 percent in placebo group to 0.7 in treated patients, a 92 percent reduction

Risk for adenomas larger than one centimeter: 7 percent in the placebo group to 0.7 percent in the treatment group, a 90 percent reduction.

Rate of repeating adenoma among patients who had previously had more than one adenoma: 13.2 percent in the placebo group to with 0.7 percent in the treatment group, a 95 percent reduction.
The rate of reduction was so pronounced that the trial's independent data and safety monitoring board stopped the trial early.

An analysis of side effects and toxicity found no difference between the treatment and placebo groups. There also was no difference in side effects requiring an overnight hospitalization, gastrointestinal side effects or cardiovascular side effects between the two groups.

"What we have shown here is that there is value in testing these agents at lower doses and in combination to determine if we can achieve the same effect without the damaging side effects," Meyskens said.

Hope For Crohn's Patients With Fistulas Found In HUMIRA/Adalimumab

2008-03-11T06:11:00.000-07:00

At the recent European Crohn's and Colitis Organization (ECCO) annual meeting in Lyon, France, Abbott Laboratories announced that HUMIRA (Adalimumab) is successful in the treatment of fistulas in susceptible Crohn's patients.

Crohn's Disease (CD) is a gastrointestinal disorder which is indicated by chronic inflammation of the wall of the digestive tract. The disease involves constant cycles of flare-ups and remission throughout the life of the patient, and without proper treatment, must be addressed surgically. It is considered an inflammatory bowel disease (IBD), similar to ulcerative colitis. Up to 43% of Crohn's disease patients develop painful and embarrassing fistulas, which are tunnels that connect affected organs to surrounding tissues such as the bladder, vagina, or skin. These are difficult to treat, can cause fecal discharge in abnormal locations, and can thus lead to incontinence, infections, and complications that will necessitate surgery.

HUMIRA, or Adalimumab works by binding Tumor Necrosis Factor α (TNF-α), an important part of the immune response pathway -- in this way it is related to infliximab and other TNF-α blockers. It has been approved in several countries for treatment of many autoimmune diseases including CD, psoriasis, and certain types of arthritis. Abbott Labs is also studying HUMIRA in pediatric CD.

The fistula study was based on data taken in the CHARM study. In a subanalysis, it was shown that fistula healing was improved with treatment with HUMIRA:

60% of patients experienced fistula healing at one year of treatment
76% of patients who experienced healing at one year sustained the healing through two years
71% of patients demonstrated a 50% reduction in the number of draining fistulas after two years of treatment
Over a two year term, fistula patients had a higher quality of life because the CD was in remission, defined as scoring greater than 170 points on the Inflammatory Bowel Disease Questionnaire (IBDQ): after 1 year, 54% of patients and after 2 years, 60% of patients achieved this score.

Sustainability of Adalimumab in Improving the Quality of Life of Patients With Fistulizing Crohn's Disease: 2-Year Data From CHARM
E. V. Loftus, Jr., J. F. Colombel, R. Panaccione, B. G. Feagan, M. A. Kamm, P. F. Pollack, J. Chao, P. Mulani
For More Information, see http://www.humira.com/

Improved Treatment For Crohn's Disease

2008-02-24T13:52:00.000-08:00

An international research study, published in The Lancet, has thrown into question the current method of treating Crohn's disease - opening the door to a safer and more effective treatment option for sufferers of the chronic disease.

"Our study clearly demonstrated that this alternative treatment method was more effective at inducing disease remission than the conventional method," said Dr. Brian Feagan, Director of Robarts Clinical Trials at Robarts Research Institute at The University of Western Ontario. Dr. Feagan coordinated the research trial and is an author on the study. "Not only were patients more likely to get their disease under control, but they were also spared exposure to steroids - the extended use of which is linked with metabolic disease and even increased mortality. It's simply a safer, more effective treatment method."

Called a "step-up" approach, the conventional treatment for Crohn's disease involves first administering steroids in order to control the patient's symptoms (abdominal pain and bloody diarrhea); the next step involves administering immune-suppressing drugs, which prepare the body to receive the third medication - an antibody that curbs the inflammatory response at the root of the disease.

The alternative strategy, called "top-down" therapy, employs early use of immune-suppressing drugs combined with an antibody in order to address the disease from the start. Symptom-treating steroids may never even be needed.

The two-year study was conducted at research centres in Belgium, Holland, and Germany and involved 129 subjects with active Crohn's disease. 64 patients received the conventional step-up treatment and 65 the combined immune-suppressing method (top-down). 60% of the top-down subjects were symptom-free by the 26th week of the study, compared to only 36% of the step-up subjects.

"This study is a milestone in the management of Crohn's disease," said lead author Dr. Geert D'Haens, of the Imelda GI Clinical Research Centre at the Imelda Hospital in Bonheiden, Belgium. "It does not look at the effects of single drug intervention but at strategies to alter the natural history of this chronic destructive condition. All 'classic' paradigms for the management of Crohn's disease need to be questioned."

The impact of the study goes beyond Crohn's disease. "We've seen similar results in top-down, step-up studies of rheumatoid arthritis," said Dr. Feagan, "suggesting that the top-down approach could be the best treatment method for other chronic auto-immune diseases such as ulcerative colitis."