Treating Relapsed or Refractory B-cell Lymphomas

Name of the Trial
Phase I/II Study of Flavopiridol in Patients with Refractory or Recurrent Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma (NCI-07-C-0081). See the protocol summary at http://cancer.gov/clinicaltrials/NCI-07-C-0081.

Principal Investigator
Dr. Kieron Dunleavy, NCI Center for Cancer Research

Why This Trial Is Important
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for up to 30 percent of new cases. DLBCL is an aggressive lymphoma, and, although many patients can be cured with current therapies, the prognosis for patients with relapsed DLBCL is often poor. Mantle cell lymphoma (MCL) is a less-common type of NHL; however, it is usually not curable with current therapies. New treatment options are needed for patients with relapsed or treatment-resistant (refractory) DLBCL or MCL.

Scientists are studying the drug flavopiridol to see if it can be effective in treating these diseases. Flavopiridol belongs to a class of drugs known as cyclin-dependent kinase (CDK) inhibitors. CDKs are proteins that help control cell proliferation. To be active, CDKs must interact with other proteins called cyclins.

MCL cells are distinguished by an excess of cyclin D1, and scientists believe that blocking the activity of this protein through CDK inhibition is a potential therapeutic strategy that may cause MCL cells to die. In addition, preliminary results suggest that flavopiridol may be active against DLBCL.

“Because there are numerous molecular targets for this drug in these diseases, we have a very good scientific rationale for investigating flavopiridol in these lymphomas,” said Dr. Dunleavy. “We hope that inhibiting these targets with flavopiridol will cause these tumor cells to undergo apoptosis, or programmed cell death.”

Although a different administration schedule of flavopiridol has been tested previously in the treatment of MCL with disappointing results, Dr. Dunleavy noted that this trial is employing a novel method of drug delivery that incorporates both continuous infusion over several hours and a bolus infusion that delivers a large initial pulse of drug.

“Originally developed for and tested in patients with chronic lymphocytic leukemia, where it showed excellent efficacy, this hybrid schedule of administration aims to achieve levels of flavopiridol that can effectively kill lymphoma cells,” Dr. Dunleavy said.

For More Information
See the list of eligibility criteria and contact information at http://cancer.gov/clinicaltrials/NCI-07-C-0081 or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

Source: NCI Cancer Bulletin. July 22, 2008

New Drugs for Multiple Myeloma Consolidation Therapy

Name of the Trial
Phase III Randomized Study of Consolidation Therapy Comprising Bortezomib and Dexamethasone with Versus without Lenalidomide in Patients with Symptomatic Multiple Myeloma Who Have Completed a Dexamethasone-Based Induction Regimen (ECOG-E1A05). See the protocol summary at http://cancer.gov/clinicaltrials/ECOG-E1A05.

Principal Investigator
Dr. Rafael Fonseca and Dr. S. Vincent Rajkumar, Eastern Cooperative Oncology Group

Why This Trial Is Important
Multiple myeloma is a type of cancer that begins in plasma cells, white blood cells that are part of the immune system. In this disease, malignant plasma cells (myeloma cells) multiply and form small lesions in the bone marrow and the solid parts of bone. Although multiple myeloma is usually not curable, advances in drug treatment and the use of stem cell transplantation have substantially increased the average survival time of patients with this disease.

Patients with multiple myeloma are often treated first with chemotherapy drugs and the steroid dexamethasone to induce remission (induction therapy). This is often followed by “consolidation therapy” with high-dose chemotherapy and stem cell transplantation. Although consolidation therapy has produced longer survival, the side effects associated with it can be severe and may dramatically affect quality of life. Doctors want to study new consolidation therapy options, using recently developed drugs, to see if they can achieve the same or better outcomes without as much risk to the patient.

In this trial, newly diagnosed patients who have undergone induction therapy will be treated with consolidation therapy consisting of dexamethasone and the drug bortezomib. Some patients will also be randomly assigned to receive a third drug called lenalidomide. Both bortezomib and lenalidomide have been approved by the FDA to treat patients with relapsed multiple myeloma, and they have shown promise in early clinical trials involving patients with newly diagnosed disease.

“One of the biggest questions in the minds of patients in this era of new drugs is, ‘Do we still need to have a transplant?’” said Dr. Rajkumar. “Autologous transplants are associated with significant morbidity and can be life changing. Both of these regimens hold the promise of high response rates that may rival what we can achieve with stem cell transplantation while being easier on patients.”

For More Information
See the list of entry criteria and trial contact information at http://cancer.gov/clinicaltrials/ECOG-E1A05 or call the NCI Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

Source: NCI Cancer Bulletin. July 8, 2008

Treatment for Advanced Carcinoid Tumors

Name of the Trial
Phase III Randomized Study of Depot Octreotide Acetate and Interferon alfa-2b versus Depot Octreotide Acetate and Bevacizumab in Patients with Unresectable Metastatic or Locally Advanced, High-Risk Neuroendocrine Carcinoid Tumor (SWOG-S0518). See the protocol summary at http://cancer.gov/clinicaltrials/SWOG-S0518.

Principal Investigator
Dr. James Yao, Southwest
Oncology Group

Why This Trial Is Important
Carcinoid tumors originate most often in neuroendocrine cells of the gastrointestinal tract, although they can arise elsewhere in the body. While most carcinoid tumors grow slowly, they are often resistant to treatment and can be life threatening when advanced. Currently, there is no treatment that has been proven to stop or slow the growth of advanced carcinoid tumors, and patients with these tumors face a dim prognosis.

Doctors are eager to find new ways to treat advanced carcinoid tumors. One strategy being studied is the inhibition of tumor angiogenesis. Carcinoid tumors tend to produce a lot of blood vessels and may be susceptible to antiangiogenesis therapy.

The monoclonal antibody bevacizumab (Avastin) has been shown to inhibit tumor angiogenesis and is approved by the FDA to treat several different cancer types. In this trial, patients with advanced carcinoid tumors that have spread (metastasized) or that cannot be surgically removed (unresectable) will be randomly assigned to receive the drug octreotide acetate along with either bevacizumab or interferon alfa. The combination of octreotide acetate and interferon alfa is often used for refractory carcinoid syndrome, a collection of symptoms – including flushing, abdominal pain, and diarrhea – caused by hormones secreted by advanced carcinoid tumors.

“In our previous phase II study comparing these combinations, the addition of bevacizumab to octreotide acetate led to rapid and sustained decreases in tumor blood flow, resulting in disease stabilization in most patients and even producing partial responses in some patients,” said Dr. Yao. “Additionally, patients receiving bevacizumab were more likely to have stable disease at 18 weeks than patients who received interferon.

“With this phase III trial, we hope to confirm these results and possibly establish bevacizumab as a standard therapy for patients with these difficult to treat tumors.”

For More Information
See the lists of entry criteria and trial contact information at http://cancer.gov/clinicaltrials/SWOG-S0518 or call the NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

An archive of “Featured Clinical Trial” columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.

Source: NCI Cancer Bulletin. June 24, 2008

Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer

Name of the Trial
Phase III Randomized Study of Adjuvant Chemotherapy Comprising Carboplatin and Paclitaxel with Versus without Bevacizumab and/or Secondary Cytoreduction Surgery in Patients with Platinum-Sensitive Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer (GOG-0213). See the protocol summary at http://cancer.gov/clinicaltrials/GOG-0213.

Principal Investigators
Dr. Robert Coleman, Dr. Scott Eisenkop, Dr. Deborah Armstrong, Dr. Thomas Herzog, and Dr. Paul Sabbatini, Gynecologic Oncology Group

Why This Trial Is Important
Ovarian cancer is one of the most common gynecologic cancers and is expected to strike more than 21,000 U.S. women in 2008. Primary peritoneal cancer and fallopian tube cancer are similar diseases that often respond to the same treatments used for ovarian cancer.

Typically, ovarian cancer is treated with surgery to remove the cancer, followed by combination chemotherapy with a platinum-containing drug (carboplatin or cisplatin) and a taxane, such as paclitaxel. Ovarian cancer that responds to chemotherapy with a platinum-containing drug is called platinum sensitive. Even if it recurs after treatment, platinum-sensitive ovarian cancer may respond again to treatment with a platinum-taxane combination.

While this common therapy does help some women live longer, doctors are eager to find better ways to treat recurrent ovarian cancer. One method under investigation is the addition of the biological agent bevacizumab to combination chemotherapy. Bevacizumab works by blocking the development of new blood vessels to tumors. Another approach, called secondary cytoreductive surgery, is performing another operation to remove the recurrent tumors.

In this phase III clinical trial, women with platinum-sensitive, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer will be assessed first to determine whether or not they are candidates for secondary cytoreductive surgery. Surgical candidacy will be determined by whether or not there is a high likelihood of complete tumor removal, based on clinical evaluation and imaging. Women found to be candidates for this surgery will be randomly assigned to undergo it or not. These women will then be randomly assigned to receive combination chemotherapy with carboplatin plus paclitaxel or the same chemotherapy plus bevacizumab, followed by maintenance bevacizumab therapy after the chemotherapy is completed.

Women who are determined to not be candidates for secondary cytoreductive surgery at the start of the trial will immediately be randomly assigned to receive carboplatin plus paclitaxel chemotherapy or the same chemotherapy plus bevacizumab, which will also be followed by maintenance bevacizumab.

“At this point, the optimal therapy for women with recurrent, platinum-sensitive ovarian cancer is notwell defined,” said Dr. Coleman. “We have seen positive results from both of these experimental therapies in early stage clinical trials, and with this trial, we are hoping to establish their benefits for women with these cancers.”

For More Information
See the lists of entry criteria and trial contact information at http://cancer.gov/clinicaltrials/GOG-0213 or call the NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

Source: NCI Cancer Bulletin. June 10, 2008

Selenium to Prevent Recurrence of Colorectal Polyps

Name of the Trial
Phase III Randomized Study of Selenium in Patients with Adenomatous Colorectal Polyps (UARIZ-00-0430-01). See the protocol summary at http://www.cancer.gov/clinicaltrials/UARIZ-00-0430-01.

Principal Investigator
Dr. M. Peter Lance, Arizona Cancer Center at University of Arizona Health Sciences Center

Why This Trial Is Important
The mineral selenium, found naturally in grains, meat, and other common foods, is being studied to see if it can help prevent several types of cancer. Proteins in the body that incorporate selenium have antioxidant properties and help repair damaged cells, which may reduce the risk of cancer. Although the relationship between selenium in the diet and cancer risk is unclear, some studies of selenium supplementation have yielded promising results. In particular, the Nutritional Prevention of Cancer Trial, designed to see if selenium supplements could prevent nonmelanoma skin cancer, found that the supplements were linked with reduced risks of lung, prostate, and colorectal cancer.

“That study was a major justification for doing a randomized controlled trial with a colorectal cancer-related endpoint,” said Dr. Lance.

In this trial, patients who have a history of colorectal adenoma – noncancerous growths (polyps) found in the colon or rectum that can be precursors to colorectal cancer – will be randomly assigned to receive either daily selenium supplements or a placebo for 3 or 5 years. At the end of the supplementation period, patients will have a colonoscopy to check for adenoma recurrence.

Whether patients in the study are treated for 3 or 5 years is at the discretion of the treating physician; some patients at higher risk of adenoma recurrence need a surveillance colonoscopy at 3 years after adenoma removal, while lower risk patients will have a surveillance colonoscopy after 5 years.

The investigators plan to follow the patients for 5 years after the end of supplementation. In addition to seeing if patients taking selenium have a lower risk of adenoma recurrence and advanced adenomas (adenomas closer to becoming cancer), the trial will characterize any side effects observed with long-term, high-dose selenium supplementation.

For More Information
See the lists of entry criteria and trial contact information at http://www.cancer.gov/clinicaltrials/UARIZ-00-0430-01

Source: NCI Cancer Bulletin. May 27, 2008