Research
Protocols offered
Treatment
BREAST
NSABP B-31: A Randomized Trial Comparing the Safety and Efficacy of Adriamycin and Cyclophosphamide Followed by Taxol to that of Adriamycin and Cyclophosphamide followed by Taxol plus Herceptin in Node-Positive Breast Cancer Patients who have Tumors that Over express HER2.
This trial looks at appropriate treatment of patients with recently resected breast cancer. The trial is open to women whose tumors involved at least on axillary node.
Recent clinical trials have shown that the most effective therapy for node positive breast cancer is the combination of Adriamycin and Cytoxan followed by Taxol. They also indicated that the presence of the HER-2/neu mutation of breast cancer cells is associated with a more aggressive tumor and a less favorable outcome. Finally, recent studies in metastatic disease have indicated that therapy with Herceptin can be extremely effective in women with advanced breast cancer whose tumors over express the HER-2/neu oncogene.
This trial looks at the addition of Herceptin to standard chemotherapy in the treatment of node-positive breast cancer. This is a two-arm randomized trial. One group of women will receive what has become standard chemotherapy in node positive breast cancer: Adriamycin and Cytoxan followed by Taxol. The second group will receive the same combination; however, they will also receive Herceptin. back to top
NSABP B-35: A Clinical Trial Comparing Anastrozole with Tamoxifen in Postmenopausal Patients with Ductal Carcinoma in Situ (DCIS) Undergoing Lumpectomy with Radiation Therapy.
This Phase III randomized, double blind study will evaluate the effectiveness of Anastrozole compared to Tamoxifen in preventing the recurrence of breast cancer (local, regional and distance recurrences, and contralateral breast cancer) in postmenopausal women with primary ductal carcinoma in situ (DCIS) treated with lumpectomy and breast radiation. In addition, this study will compare adjuvant Anastrozole to Tamoxifen in terms of time to invasive breast cancer, ipsilateral recurrence, contra lateral breast cancer, other non-breast second primary cancers, osteoporotic fractures, disease-free survival, and overall survival. This trial will accrue 3000 patients and the accrual goal is expected to be reached after 5 years.
It is estimated that there will be 192,200 new invasive breast cancers detected in the US in the next year. In addition, there will be 30,000-40,000 new cases of DCIS each year. Two protocols carried out by the NSABP have clarified several controversial issues about the nature of DCIS and alternative approaches to managing this disease. Together the two trials showed that breast conserving surgery and radiation therapy were appropriate for DCIS. Also, prior NSABP adjuvant trials have reported that Tamoxifen decreases the incidence of tumor recurrences in the breast and helps reduce the rate of new primary tumors in the opposite breast. This suggests that Tamoxifen can interfere with the development of primary invasive breast cancer or with the progression from DCIS to invasive cancer.
The success of Tamoxifen in lowering all rates of recurrence encourages the search for more effective and or less toxic agents to control the stimulation and growth of precancerous and cancerous cells in the breast. Although Tamoxifen therapy is effective, women still relapse or suffer serious side effects such as endometrial cancer, vascular complications and less serious but bothersome problems that included hot flashes and genitourinary symptoms. One reason for relapse and failure for patients on Tamoxifen may be the partial agonist properties of Tamoxifen and the lack of complete suppression of estrogen receptor (ER) signaling. Partial agonist properties also cause some of Tamoxifen's side effects, including endometrial stimulation, which can lead to hyperplasia and cancer. Drugs that do not have estrogen-agonist effects and that can reduce or eliminate signaling through the estrogen receptor could reduce the risk of relapse, increase overall survival, and or improve quality of life by reducing side effects in women with early-stage breast cancer. The reduction of circulating estrogen levels by an aromatase inhibitor may meet these criteria. back to top
CTSU NCIC MA27: A Randomized Phase III Trial of Exemestane Versus Anastrozole with or without Celecoxib in Postmenopausal Women with Receptor Positive Primary Breast Cancer.
The annual hazard of recurrent metastatic disease and mortality in women with receptor positive primary breast cancer is improved for at least 10 years following the administration of five years of postoperative adjuvant Tamoxifen. However, only 1/3 of women at risk of dying from breast cancer are protected by Tamoxifen in the 10 -15 years after diagnosis. In addition, Tamoxifen has serious, albeit rare, drawbacks to its use include an elevated risk of endometrial cancer and thromboembolism. There is a need for improving the therapeutic index of adjuvant breast cancer therapy. The aromatase inhibitors and Celecoxib may achieve this.
Recently the ATAC trial has demonstrated that anastrozole, an aromatase inhibitor, is superior to Tamoxifen in postmenopausal women, causing a significant reduction in the risk of disease recurrence after a median follow-up of 33.3 months (Hazard Ratio 0.83) In addition, anastrozole treatment resulted in a significant reduction in contralateral new breast cancers (OR 0.42). The side effect profile and end-organ effects from anastrozole also seem superior to Tamoxifen in the ATAC trial, with the exception of fewer clinical fractures and musculoskeletal disorders in women given Tamoxifen. Based on these data, anastrozole has been approved as an optional adjuvant therapy for postmenopausal receptor positive breast cancer in the United States. Exemestane is an aromatase inhibitor with properties similar to anastrozole.
Cox-2 is over expressed in breast tumors. Preclinical studies have shown chemopreventive and chemotherapeutic effects of Celecoxib in rodent models of breast cancer. While both Exemestane and Celecoxib are independently active in this model, in combination they appear synergistic both in preventing new tumors and in reducing existing tumor burden in the animals.
There is thus a rationale for determining the effects of Exemestane alone and in combination with Celecoxib as a way to improve the outcome of women with breast cancer. back to top
LUNG
CTSU NCIC BR.19: A Phase III Prospective, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Antagonist, ZD1839 (Iressa), In Completely Resected Stage IB, II, and IIIA Non-Small Cell Lung Cancer.
This is a protocol designed to determine if treatment for early stage lung cancer with a new oral drug which targets growth factor receptors can be effective in reducing recurrence. The standard of care for patients with I-B and stage II lung cancer is no additional therapy after surgical resection. Patients with stage III A disease, are often offered chemotherapy and radiation before surgery. For those patients who are noted to be III A after surgery the treatment may include chemotherapy, but the benefit of chemotherapy after surgery in stage III A patients has not definitively proven beneficial. Even with complete surgical resection all of these subcategories of patients have a chance of recurrent disease. Patients with stage I-B have about a 60% 5-year survival; patients with stage II disease have about a 45% chance survival.
Iressa is an oral drug that has been used through clinical trials in many cancers but most recently in metastatic non-small cell lung cancer. Iressa has been shown to be effective in approximately 20% of patients with metastatic cancer who have not responded to prior therapies. Early stage Lung cancer patients who have not received prior therapy may have a higher response rate to Iressa. Iressa is generally well tolerated, with the common side effects of a mild acne-type rash and some diarrhea. The advantage of this drug is that it is taken orally and does not cause many of the systemic side effects associated with chemotherapy. The dosage is 250mg per day for two years. Patients will be randomized to either receive the drug or placebo, both of which are provided by the study. Neither the patient, their doctor, the pharmacist, or the study monitor will know if placebo or the Iressa has been assigned to the patient. back to top
SWOG S0124: A Randomized Phase III Trial of Cisplatin and Irinotecan (NSC-616348) versus Cisplatin and Etoposide in Patients with Extensive Stage Small Cell Lung Cancer (E-SCLC).
This is a trial comparing what is considered the standard of care for extensive stage small cell lung cancer, Cisplatin and Etoposide, with a new combination chemotherapy, Cisplatin and Irinotecan. Extensive stage small cell lung cancer is a seriously disease over a 90% fatality rate. Chemotherapy has been shown to be very effective at inducing a temporary remission and improving quality of life.
In the last five years a new drug has become available called Irinotecan. This is a new class of drug called a topoisomerase 1 inhibitor. It has been used extensively in advanced colon cancer and has been shown to improve survival rates in that disease when added to standard therapy. Irinotecan therapy has been expanded to include use in lung cancer and has been shown to be 22% more effective then standard chemotherapy combinations.
In this combination therapy the Cisplatin is the most toxic drug and will be included in both treatment combinations. It can cause significant nausea and vomiting and can occasionally damage the kidneys and cause neuropathy. Etoposide causes fairly significant myelosuppression as well as moderate nausea and vomiting. Irinotecan causes less myelosuppression and moderate nausea as well. Its most significant side effect is severe and occasionally life-threatening diarrhea, although the doses of Irinotecan to be used in this study are very low. Research associated with this study will test the hypothesis that a certian genetic expressions is associated with Irinotecan toxicity and another different genetic expression is associated with response to Irinotecan therapy. A small blood sample is needed to evaluate these genetic expressions. back to top
NON-HODGKIN’S LYMPHOMA
IDEC 106-10: A Prospectively Rand. Ph.III Multi-Ctr. Controlled Trial To Evaluate the Safety & Efficacy of the Zevalin™ Therapeutic Regimen + Rituxan® Compared w/Rituxan® alone in Pts. w/Relapsed or Refractory Follicular Non-Hodgkin’s Lymphoma
An antibody is a type of protein that helps protect the body against foreign materials such as bacteria (germs) and viruses. A monoclonal antibody is a laboratory-produced substance that recognizes a specific protein on lymphoma cells. Zevalin and Rituxan are both monoclonal antibodies. The Zevalin antibody is a mouse antibody, whereas Rituxan is part mouse and part human. These two antibodies recognize proteins found on lymphoma cells. Rituxan causes the body’s immune system to destroy the lymphoma cells, while Zevalin carries radioactivity to destroy lymphoma cells. The radioactive particles 111Indium and 90Yttrium are attached to Zevalin. The 111Indium Zevalin can be recognized by a gamma camera that scans your body. These images enable the physician to see and evaluate the distribution of the 111Indium Zevalin antibody in your body. 90Yttrium Zevalin is then used to deliver radiation therapy to treat your NHL and cause lymphoma cells to die, possibly resulting in remission (disappearance of tumor) of your disease.
Previous studies have determined the most effective and safe dosages of the Rituxan and Zevalin regimens. About 500 patients in clinical studies received from 1 to 8 infusions of Rituxan at various dosage levels. Since FDA approval, over 200,000 patients have been treated with Rituxan. Approximately 700 patients in clinical studies received Zevalin treatment at various dosage levels. Since FDA approval, over 300 patients have been treated with Zevalin. back to top
OVARIAN
SWOG S0211: A Phase II Trial of STI571 for the Treatment of Platinum and Taxane Refractory Stage III and IV Epithelial Ovarian Cancer and Primary Peritoneal Cancer.
This is a clinical trial for women who have progressive cancer within six months of completing three or less courses of standard chemotherapy for Ovarian Cancer and Primary Peritoneal Cancer. STI-571 is also called “Gleevec.” Gleevec been approved by the FDA for use in Chronic Myelogenous Leukemia and Gastrointestinal Stromal Tumors. Gleevec is an oral drug that blocks specific protein “receptors” on cancer cells which causes their destruction with very little effect on normal cells. Ovarian Cancer and Primary Peritoneal Cancer cells may have specific protein receptors that make them susceptible to Gleevec. The patient’s tumor tissue will be tested to see if these receptors are present and if so, then the patient would be eligible for this study. The common side-effects of Gleevec are usually not as severe as those associated with chemotherapy. They can include headache, nausea, fatigue, mild skin rash, intestinal gas, weight gain and edema. The decreased side-effects should enhance the patient’s quality of life. Gleevec will be supplied free of charge to the patient as long as they show an effective response to the drug and remain on the clinical trial.
GOG 0182: A Phase III Randomized Trial of Paclitaxel and Carboplatin Versus Triplet or Sequential Doublet Combinations in Patients with Epithelial Ovarian or Primary Peritoneal Carcinoma.
A phase III prospectively randomized study evaluating different combinations of chemotherapy for Epithelial Ovarian Cancer. This is the most common type of ovarian cancer.
The chemo is given following surgery. Although there are 5 separate treatment arms of the study, which appear confusing at first, they all contain the "standard" chemotherapy used in North America, carboplatin and taxol. In fact, this is the standard comparison arm.
The other treatments merely add a third drug, which has promising activity in this disease, or alternates a different chemotherapy combination, with carboplatin and taxol.
The additional drugs are all FDA-approved and have a proven record in ovarian cancer by themselves. Their addition is being evaluated to determine if they can add efficacy to the standard carboplatin-taxol combination, without adding unwelcome toxicity. back to top
GOG 0170D: A PHASE II EVALUATION OF BEVACIZUMAB (rhuMAB VEGF) (NSC #704865, IND #7921) IN THE TREATMENT OF PERSISTENT OR RECURRENT EPITHELIAL OVARIAN OR PRIMARY PERITONEAL CARCINOMA
This is a single armed study where all the participants receive the new drug, Bevacizumab. This is a monoclonal (bioengineered) protein targeted against a protein on the cell surface that triggers the growth of blood vessels.
This drug is nearly FDA approved after studies have shown a significant benefit in advanced colorectal cancer. It has been well tolerated although there have been reports of hypertension, bleeding into tumors, excess protein loss in the urine, and allergic reactions reported. Overall, it has a much better safety profile than most chemotherapeutic drugs.
Participants in this study are not curable by present treatments. They commonly receive a parade of various chemotherapeutic drugs that are partially effective and may prolong their lives. The hope is that Bevacizumab will significantly prolong their life with little if any toxicity.
The drug is provided free to participants. back to top
GOG 0198: A Randomized Study of Tamoxifen versus Thalidomide (NSC#66847) in Patients with Biochemical-Recurrence-Only Epithelial Ovarian Cancer, Cancer of the Fallopian Tube, and Primary Peritoneal Carcinoma After First Line Chemotherapy.
This study will randomize participants to receive either Tamoxifen or Thalidomide in patients whom have a rise in their tumor marker (biochemical recurrence), as a sign of recurrent cancer. These patients are commonly asymptomatic. The dilemma posed for the physician and the patient has been whether to observe without therapy or start a chemotherapeutic program in this setting. The hope of this study is to use a non-chemotherapy approach, either Thalidomide or Tamoxifen, in patients with increasing tumor marker (CA-125), for biochemical recurrence. These patients are asymptomatic and have previously received chemotherapy after their initial diagnosis and surgery.
Tamoxifen is a well-known hormone therapy for breast cancer. It has been used for ovarian and related malignancies. Although its’ response rate is quite low, patients do tolerate it well. The other option in the study, Thalidomide, has FDA approval for use in myeloma. Thalidomide is beginning to be used in several other malignancies. Thalidomide is different from standard cytoxic chemotherapy, and modulates many of the molecules, or growth factors responsible for the growth and progression of cancer. It is reasonable well-tolerated, but does have the risk of being sedative since it was initially developed as a sleeping medication, and may also cause damage in the peripheral nerves, skin rash, swelling or edema of the ankles, as well as constipation. The most notorious side effect of Thalidomide is birth defects; thus, patients will be screened carefully to avoid any women who are pregnant or who could become pregnant.
Both drugs are given orally. Thalidomide will be supplied by the study, but Tamoxifen will be bought commercially.
The objective of the study will be to compare the freedom from relapse, as well as the toxicities and complications, in patients receiving Tamoxifen or Thalidomide in this setting. back to top
GOG 227C: A PHASE II EVALUATION OF BEVACIZUMAB (rhu MAB VEGF) (NSC #704865 IND #7921) IN THE TREATMENT OF PERSISTENT OR RECURRENT SQUAMOUS CELL CARCINOMA OF THE CERVIX
This study will evaluate the effectiveness of Bevacizumab, now FDA-approved for use in metastatic colorectal cancer under the name "Avastin", in recurrent cervical cancer. This drug is a monoclonal antibody (a bioengineered protein) that targets "vascular endothelial growth factor", or VEGF. This molecule encourages the growth of new blood vessels into tumors that it required for their growth. Thus, Bevacizumab is an "Anti-VEGF" and decreases the production and growth of blood vessels nourishing a tumor.
Eligible patients will be those with either biopsy-proven recurrent or persistent squamous cell carcinoma of the cervix. They must have measurable disease and have previously received at least one prior chemotherapy for advanced, recurrent, or persistent cervical cancer. This would not include chemotherapy used as a radiation enhancer. There are no curative second- or third-line chemotherapies in this setting.
As in most chemotherapy trials, satisfactory organ and metabolic function is required. Pregnant and nursing women are prohibited.
All patients will receive Bevacizumab every three weeks as long as there is no progression of disease or intolerance of the drug. Bevacizumab is given as an intravenous infusion; the first infusion will run over 90 minutes, the second infusion over 60 minutes, and thereafter, over 30 minutes, provided the infusion is well tolerated. The drug is provided free of charge.
As opposed to cytotoxic chemotherapy, there is no anticipated nausea, bone marrow suppression. Possible side-effects include: hypersensitivity or allergic reactions, high blood pressure, delayed wound healing, hemorrhage (usually into a tumor), thrombosis, excess protein loss in the urine. There have been additional side-effects reported but they are rare and usually not severe. back to top
PANCREAS
CTSU ECOG 4201: A Randomized Phase III Study of Gemcitabine in Combination with Radiation Therapy versus Gemcitabine Alone in Patients with Localized, Unresectable Pancreatic Cancer.
This is a national cooperative group study funded by the NCI for patients who have unresectable pancreatic cancer, yet remain active with a good performance status. Gemcitabine is recognized as the most effective and only FDA-approved chemotherapeutic drug for pancreatic cancer. However, we know it can be synergistic with radiation, both in toxicity, as well as for therapeutic benefit. This study is an attempt to improve on our dismal record in treating patients with unresectable pancreatic cancer by utilizing a program of Gemcitabine at a lower dose with radiation given concurrently versus a standard control arm of Gemcitabine alone. back to top
There have been several other studies that have used Gemcitabine in a similar fashion with radiation. Albeit smaller studies, they have shown an improvement over what had been used before, which was 5-FU with radiation. Thus, the combined treatment arm of Gemcitabine and radiation has been published before in smaller groups of patients, and appears to be tolerable without undue toxicity. back to top
Control
BREAST
- NCCTG N00C9: The Use of Ginkgo Biloba for the Prevention of Chemotherapy-Related Cognitive Dysfunction
Chemotherapy can be associated with attention fatigue, neurocognitive dysfunction or other cognitive deficits, sometimes generally referred to as “chemo brain.” This entity is being increasingly recognized in the medical literature. The etiology is unclear, and may relate to a neurotoxicity associated with chemotherapy regimen. In breast cancer patients, it may relate to the role of estrogen in cognitive functioning. The Chinese herb, Ginkgo biloba, has been studied in relation to cognitive functioning. It has been tested in relation to cognitive functioning, in dementia, and in Alzheimer’s disease. The proposed study will compare Ginkgo biloba to placebo. Patients will take the supplied tablets beginning with the start of chemotherapy through a period ending one month beyond the completion of chemotherapy. This trial is a randomized, double-blind study. back to top
PROSTATE
- NCCTG N00CB: Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Gabapentin in the Management of Hot Flashes in Men
Hot flashes can be a problem for men treated with hormonal therapy for prostate cancer. It is a quality of life issue similar to the menopausal symptoms in women. This study looks at gabapentin as a treatment. It is a placebo-controlled trial. Three out of every four men on the study will get study drug, although at different strengths. back to top
