Clinical Trials at NIH Clinical Center

A clinical trial is recruiting patients with advanced colorectal cancer to test response rates when and oral drug Nexavar® (sorafenib) is added to to Erbitux® (cetuximab).  In addition, researchers will be evaluating the safety and side effects of the combination.

Erbitux blocks receptors on the surface of cancer cells for EGFR, a protein that stimulates growth and multiplication of cancer cells.  Nexavar works in a different way to block two other substances that promote cancer growth:  VEGF and raf kinase.  By blocking additional cancer cell activity, the research team hopes to increase the number of responses to treatment and also increase time until cancer begins to grow again.

In order to be eligible for the trial, patients must

• Have confirmed metastatic colorectal cancer
• Have already had their cancer progress on at least one chemotherapy regimen for metastatic cancer
• Have tumors that can be measured.
• Have tumors that can be reached for biopsies.
• Have tumors that are positive for EGFR
• Have received one or more 5FU (fluorouracil) containing chemotherapies.

Patients who are not eligible include those

• who are able to have their tumors surgically removed.
• with cancer that has spread to their brains.
• who have already received either Erbitux or Nexavar
• who cannot swallow pills
• are pregnant or nursing

The trial is being conducted at the NIH Clinical Center at the National Institutes of Health in Bethesda MD,outside of Washington, DC.

Dr. Shivaani Kummar is the principal investigator for the study.  She explains,

The majority of patients with metastatic colorectal cancer have tumors expressing EGFR. Cetuximab is approved by the FDA to treat EGFR-expressing metastatic colorectal cancer, but unfortunately, it produces significant tumor shrinkage in only about 10 percent of patients when used as a single agent. With this trial, we hope to see an improved response rate by augmenting the activity of cetuximab with an additional drug that blocks other processes important for tumor growth and cell proliferation.

Patients will be admitted to the hospital at the NIH Clinical center for two or three days at the beginning of treatment.  From then on, there will be weekly out-patient visits.  It is possible for outpatient treatment to be coordinated with local oncologists to reduce travel to Bethesda.

There is no cost for treatment at the NIH Clinical Center.  Patients will need to pay their own travel costs for the initial screening visit, but after that the National Cancer Institute will pay for all travel costs, as well as providing a small subsidy for housing and meals.

For more information contact:

Shivaani Kummar, M.D.
Principal Investigator
Phone: 301-435-5402
kummars@mail.nih.gov

Janelle Bingham, R.N.
Referral Coordinator
Phone: 301-435-2715
jbingham@mail.nih.gov

More information about the study is on the National Cancer Institute clinical trials website.

Adding Erbitux® to a standard colorectal cancer chemotherapy treatment that also included Avastin® did not increase mortality according to initial reports of a randomized clinical trial for patients with advanced colorectal cancer.

The trial — CAIRO2 — conducted in Europe compared CAPOX plus Avastin to CAPOX plus both Avastin and Erbitux.  CAPOX combines the oral chemotherapy drug Xeloda® (capecitabine) with intravenous Eloxatin® (oxaliplatin.) Patients in the trial had advanced (metastatic) colon or rectal cancer, and this was their first chemotherapy for advanced cancer.

755 patients took part in the trial.  The study measured how long patients lived before their cancer grew or progression-free survival.

Analyzing safety information for the first 400 patients, researchers found an expected difference in serious toxicity when Erbitux was added to the standard treatment.  However, this was entirely due to skin rash, a known and common side effect of Erbitux.  Overall grade 3 and 4 toxicity from all causes was 81 percent in the experimental arm and 72 percent in the arm without Erbitux.

There was no increase in gastrointestinal side effects treatment-related deaths.

This analysis did not include information on the effectiveness of the new combination.

Writing in the Annals of Oncology, the Dutch Colorectal Cancer Group, concluded,

The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of advanced colorectal cancer appears to be safe and feasible. No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed.

SOURCE: Tol et al., Annals of Oncology, advanced access published online February 13, 2009.

25 mcg/hr Duragesic® patches manufactured by ALZA corporation and sold by PriCara® or Sandoz in the United States are being voluntarily recalled.  The recalled lots have expiration dates on or before December, 2009.  Duragesic patches manufactured by ALZA and sold in Canada are also being recalled.

The recall does not affect other Duragesic strengths:  12.5, 50, 75, or 100 mcg/hr. Durogesic™ patches sold in Europe, Latin America, and Asia are also not included in the recall.

The patches may have a cut along the side of the reservoir that contains fentanyl gel potentially letting the gel leak into the patch packaging.  Fentanyl is a powerful opioid drug, and exposure to the gel could lead to dangerous effects which can be fatal.

Anyone with 25 mcg/hr Duragesic patches should check the box and the individual foil packages for expiration dates.  Do not open the foil packaging if you have any question about the safety of the patch inside.  Do not handle a potentially damaged patch.

Contact your doctor if you have concerns about what to do about pain management.

In the news release announcing the recall, Johnson and Johnson, the parent company of PriCara said,

Anyone who comes in contact with fentanyl gel should thoroughly rinse exposed skin with large amounts of water only; do not use soap. Immediately dispose of affected patches with cut edges by flushing them down the toilet, using caution not to handle them directly. Patches with a cut edge that have leaked gel will not provide effective pain relief.

Johnson and Johnson also says,

Anyone with 25 mcg/hr DURAGESIC patches being recalled should call 800-547-6446.

Anyone with 25 mcg/hr Sandoz Inc. patches being recalled should call 800-901-7236.

Patients using fentanyl patches who have medical questions should contact their health-care providers.

The FDA has previously issued a public health advisory about the safe use of fentanyl patches.

WHAT THIS MEANS FOR PATIENTS

Patients and their caregivers who are using the 25 mcg/hr Duragesic patches to manage pain should immediately check the box or foil package to see if the expiration date is on or before December 2009.

If so, do not open the foil package and do not handle the patch itself directly.

If you do get some gel on your hands, rinse them immediately with large quantities of water without soap.

All fentanyl patches of any strength should always be disposed of by putting sticky sides together and flushing down the toilet.  Don’t handle the 25 mcg patches directly while disposing of them.

Call your doctor about managing pain relief.

Call either Duragesic (800-547-6446) or Sandoz (800-901-7236) for information about the next steps in returning the patches.

A small fiber-optic probe the size of a pen that analyzes light shone on colorectal tissue just inside the rectum can predict whether or not there are precancerous polyps in other places in the colon.  Using enhanced backscattering spectroscopy or EBS, light that scatters back into the probe can provide a great deal of information about the smallest details of cells, including changes in normal cells that reflect more dangerous precancerous changes elsewhere in the colon.

Its inventors believe that it will be an important screening tool for colorectal cancer, accurately predicting people who need to have a full colonoscopy to find precancerous polyps or early colon cancer.

Vadim Backman, professor of biomedical engineering at the McCormick School of Engineering at Northwestern University in Chicago, developed the technique and has been testing it with Dr. Hemant Roy, gastroenterologist and associate professor at Northwestern’s Feinberg School of Medicine. They call it four-dimensional elastic light-scattering fingerprinting (4D-ELF).

In both mice and a pilot study of human colonoscopies, analysis of backscattering in normal tissue was able to predict the risk for precancerous changes throughout the colon.

In the pilot testing on 63 people undergoing colonoscopy, 4D-ELF was able to predict 100 percent of precancerous polyps.  Although some people without polyps also were identified as potentially needing colonoscopy, the screening with 4D-ELF reduced the need for colonoscopy by two-thirds.

Writing in Clinical Cancer Research, Dr. Roy said,

Finally, in pilot human studies, we observed that LEBS analysis of the endoscopically normal mucosa was able to detect differences in patients who harbored adenomas when compared with those who were neoplasia free. Thus, the technical advance of LEBS may potentially translate into a practical means for colon cancer screening.

With funds from the National Cancer Institute, Dr. Roy is testing 4D-ELF on 1,250 people who are having colonoscopies with the goal of developing rules for who may need a full colonoscopy based on 4D-ELF screening and who does not need further testing.  He will also be looking at patients with inherited colorectal cancer syndromes (HNPCC and FAP) to see if the probe can be helpful in surveillance for them.

The technology is also being explored for pancreatic cancer where the probe is used during routine endoscopic biopsies of the duodenum to find cancer in the pancreas.  Screening high risk families may find pancreatic cancer early enough to cure it.

An article on Dr. Backman’s research appeared in the Chicago Tribune.

SOURCE: Roy et al. Clinical Cancer Research, Volume 12, February 2006.

WHAT THIS MEANS FOR PATIENTS

Enhanced backscattering spectroscopy analysis is still experimental and is not available outside of clinical research.

While it shows promise as a colorectal screening method, people who need colorectal cancer screening should not delay their own screening in anticipation of this technology.

All people of average risk should be screened for colorectal cancer by one of the currently approved methods:  fecal occult blood tests, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy.

People with higher than average risk should be screened with colonoscopy on a schedule determined with their doctors.

The Conservatives’ favorite, Mitt Romney (MA), ended his bid for the GOP Presidential nomination on Thursday afternoon. Romney said it was time for him to step aside in order for the Republicans to launch a national campaign against Senator Hilary Clinton and Senator Barack Obama.

Romeny’s departure all but assures that Senator McCain will win the Republican nomination. McCain has had a difficult time winning over the hearts of the conservatives in his own party. Some have even vowed not to vote if he is the nominee.

Former Governor Mike Huckabee (AK), a distant third in the fight, has vowed to continue his campaign.