Researchers at the National Cancer Institute are testing a new treatment for solid tumors, including colorectal cancer.  They will harvest lymphocytes (white blood cells) from  cancer patients’ blood, modify those cells in the laboratory to recognize the p53 protein, and return them to the body.

Patients who have exhausted standard cancer treatments are being recruited to participate in a clinical trial of the experimental approach.  The phase II trial is being conducted at the NIH Clinical Center in Bethesda, MD.

p53 is a tumor suppressor gene.  Normally its job is to recognize damaged DNA in cells, prompt other genes to repair the damage if possible, or destroy the cell if the DNA cannot be fixed. However, the p53 gene is mutated or completely missing in more than half of human cancers.  Mutated or missing p53 genes cannot control cell division and growth, and this uncontrolled growth leads to cancer.

Protocol 07-C-0003

What is being tested? 

Whether or not T-lymphocytes can be modified outside the body to recognize and destroy the p53 protein and shrink cancer tumors.  In addition, patients will receive chemotherapy and interleukin-2 to stimulate the immune system and increase the chance that the newly-engineered lymphocytes will work.

Who is eligible? 

• Patients with colorectal or other solid tumors that have spread (metastatic) and are no longer responding to standard treatments.
• Patients must overexpress the p53 protein.
• There are also more specific medical requirements which can be discussed with the research staff.

What will be done during the trial?

• Lymphocytes will be removed from the blood, altered in the laboratory, and reintroduced into the patient’s blood stream.
• Patients will receive preparatory chemotherapy and interleukin 2 before the new lymphocytes are returned to the body.
• Initially, patients will spend about two weeks in the hospital for treatment.  They will return to the NIH Clinical Center four to six weeks later for evaluation and will then be followed in Bethesda every month.

Where is the clinical trial available?

NIH Clinical Center
National Institutes of Health
NCI, Surgery Branch, Tumor Immunology Section
10 Center Drive
Bethesda, Maryland 20892

The NIH Clinical Center in Bethesda is located just outside of Washington, D.C.

Are there costs?

There is no charge for medical care received at the NIH Clinical Center.  Patients will have to pay for their transportation to Bethesda for an initial evaluation, but once accepted into the trial, transportation to and from NIH will be paid by NCI.  In addition, NCI will provide for food and lodging costs for out-patient visits.

The study is being led by Stephen A. Rosenberg, MD, PhD.  Dr. Rosenberg is Chief of Surgery at the National Cancer Institute in Bethesda and head of the Tumor Immunology Section

For more information or to be considered for the trial, contact

Linda Williams, R.N.
Research Nurse
Phone: 1-866-820-4505 (Toll free)
Fax: 301-451-1927
ncisbirc@mail.nih.gov

June A. Kryk, R.N.
Research Nurse
Phone: 1-866-820-4505 (Toll free)
Fax: 301-451-1927
ncisbirc@mail.nih.gov

Protocol 07-C- 0003: Phase II Study of Metastatic Cancer That Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-p53 TCR-Gene-Engineered lymphocytes.

On January 26, 2007 Amgen sent information to the medical community informing them of safety concerns when Aranesp® (darbepoetin alfa) was used to treat anemia in cancer patients who were not receiving chemotherapy.

In a large, randomized clinical trial, Aranesp® was compared to a placebo to reduce the need for red blood cells transfusions.  Patients in the trial were not receiving chemotherapy, nor were they expected to be.  Currently, Aranesp® is not FDA approved to be used with these patients.

After the sixteen-week treatment period, there was no statistically significant difference in the need for transfusions between the Aranesp group and those getting a placebo.  However, there were more deaths among the Aranesp patients.

In the letter, Sean Harper, MD, who is Amgen’s corporate chief medical officer, reported:

The final analysis of the initial 16-week treatment period did not show a statistically significant effect on  the primary efficacy endpoint (Hazard ratio 0.89; 95% Confidence Interval: 0.65, 1.22), with an incidence of RBC transfusions of 24% in the placebo vs. 18% in the Aranesp group, p=0.15.

In the 16-week treatment phase of the study, more deaths were reported in the Aranesp treatment group (26% (136/515)) than the placebo group (20% (94/470)). With median survival follow-up of 4.3 months the absolute number of deaths was greater in the Aranesp treatment group (216/470=46% and 250/515=49% for the placebo and the Aranesp arms, respectively, Hazard Ratio 1.25; 95% Confidence Interval: 1.04, 1.51). Follow-up of surviving patients continues.  Details of this study will be presented and published in a peer-reviewed setting as soon as possible.

Amgen says that Aranesp® should only be used “in accordance with its approved product labeling for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy.” The recent study does not support its use for general fatigue or anemia in people with cancer who are not undergoing chemo.

An article about the study is in the New York Times.

Disclosure: C3 accepts unrestricted educational grants and charitable donations from Amgen along with other pharmaceutical and biotech companies. Our corporate sponsor and policy page can be found on this page.

The Canadian Province of Ontario has announced a widespread program to screen residents in the province for colorectal cancer.  The effort is two-pronged

• Screening all people over 50 with fecal occult blood tests (FOBT).
• Reaching and testing people with a family history of colon or rectal cancer with colonoscopy.

Those who test positive for hidden blood in their stool on the FOBT will have a follow-up colonoscopy to rule out advanced polyps or colorectal cancer.

George Smitherman, Ontario Minister of Health, said that $193.5 million would be devoted to the program over the next five years.

In a telephone interview with the Toronto Globe and Mail, Barry Stein, President of the Colorectal Cancer Association of Canada, said,

We believe this program will not only save lives but it is also economically advantageous in view of the high cost of treatment in Canada. We will continue our efforts to ensure that all Canadians benefit from similar programs in the future.

In 2006, 20,000 Canadians were expected to be diagnosed with colorectal cancer in 2006 and 8,500 died of it, including 3,100 in Ontario.

Screening can prevent colorectal cancer by finding and removing polyps, known as adenomas, that can develop into cancer.  Screening also leads to early detection of colon and rectal cancers when they are most curable.

More information from CBC News, the Toronto Sun., and the Toronto Star.

According to the new American Cancer Society’s Cancer Facts and Figures 2007, 2,204 fewer people died from colorectal cancer in 2004 than 2003, the latest years where cancer deaths numbers are available.  Decline in death from colon and rectal cancer was the largest contributor to an overall reduction in cancer deaths.

The trend is expected to continue in 2007 with fewer people diagnosed with colorectal cancer and fewer people dying from it.  Incidence and death rates are also steadily declining.  From 1990 through 2003, the death rate from colorectal cancer has been cut by 25%.

Colorectal cancer is the second leading cause of cancer death in the United States.  In 2007, 52,180 men and women will die of colon or rectal cancer.  Only lung cancer is a bigger killer.

In 2007, the American Cancer Society estimates that 153,760 people in the US will be diagnosed with colorectal cancer — 112,320 in the colon and 41,410 in the rectum. 

Men and women are equally affected by colorectal cancer.  79,130 men will hear that they have colorectal cancer in this year, while 74,630 women will be diagnosed.  Even worse, 26,000 men and 26,180 women will die.  Over their lifetime, men have a 1 in 17 chance of getting colorectal cancer, women 1 in 19.

ACS attributes the reduction in new colorectal cancers and deaths from colorectal cancer to:

• Increased screening rates that find pre-cancerous polyps and prevent the disease from ever occurring.
• Earlier detection of colon and rectal cancers due to improved screening.  Colorectal cancer found in its earliest stage is more than 90% curable.
• Improved treatment options.

In discussing the meaning of the new numbers, Carlea Bauman, Executive Director of C3: Colorectal Cancer Coalition, said,

These statistics are encouraging and they reflect the hard work that has gone into fighting colorectal cancer. But they will provide little comfort to the 154,000 men and women will be diagnosed with colorectal cancer or to the loved ones of the 52,000 people who will die from colorectal cancer this year. Now is not the time to rest on our laurels.

We encourage everyone to know their risk for colorectal cancer, get screened, and be aware of the symptoms of colon or rectal cancer.  C3 and its advocates are also working hard to increase funding for research into treating and preventing this devastating disease.

Cancer Facts and Figures is based an annual statistical study done by the American Cancer Society and reported in the January 2007 issue of CA: A Journal for Clinicians.

Last week, the US House of Representatives passed legislation that will provide federal funding for stem cell research. C3: Colorectal Cancer Coalition believes that stem cell research holds promise for expanding medical breakthroughs, and we support legislation that will give the researchers the tools they need to fight cancer and other diseases. This is why we chose to add our name to a letter that was sent to the US Senate and House of Representatives last week. The letter was signed by over 500 patient advocacy groups, health organizations, research universities, scientific societies, and religious groups.

From the letter:

The legislation, HR 3, will allow the federal government to fund stem cell research that includes donor-approved excess embryos from in vitro clinics that have been donated by the patients specifically for research (which currently get discarded). This would expand the number of stem cells currently available to researchers.

From the letter:

The Stem Cell Research Enhancement Act is pro-patient and pro-research. A vote for the Stem Cell Research Enhancement Act will be considered support of more than 100 million patients in the U.S. and substantial progress for research.

The bill will now proceed to the Senate and, hopefully, on to the President’s desk for signing. As you may recall, he vetoed similar legislation last year. We sincerely hope the President will consider the life-saving potential that stem cell research holds and will sign this legislation into law.

Also, as we told you in December, C3 was closely monitoring the appropriations situation currently facing Congress. In the first week of January, C3 was one of 200 organizations who signed onto a letter to the Democratic leadership calling on them to provide at least $7 billion above the President’s budget request for health, labor and education programs (including cancer research). The letter stated in part:

A full year continuing resolution for FY 2007 at the FY 2006 levels would leave these critical programs $2 billion short of the goal established by the full Senate when it adopted the Specter-Harkin budget amendment as well as the commitment made by the House leadership to significantly increase funding for these urgent priorities. Further, failure to meet these commitments would result in total funding for these programs $2 billion below the FY 2005 level.

We learned last week that the letter was well-received by the leadership in the House and Senate who oversee such funding. We are hopeful that, as Congress debates whether or not to increase funding and resources for one war that they will not forget that the war on cancer rages on.