Clinical Trials Web

Results From Latest U.S. Study Of NX-1207 For Benign Prostatic Hyperplasia

2008-03-13T04:04:00.000-07:00

Nymox Pharmaceutical Corporation (NASDAQ: NYMX) announced that results from the Company's new multi-center U.S. Phase 2 study showed evidence that the Company's proprietary drug NX-1207 can markedly reduce the incidence of nighttime urination (nocturia), a particularly bothersome symptom associated with benign prostatic hyperplasia (BPH). After 90 days, subjects treated with a therapeutic dose of NX-1207 had a mean % reduction in nocturia symptom score of 41% versus 4% for subjects treated with finasteride, an approved BPH treatment. This improvement was statistically significant (p<.001).

Having to repeatedly get up in the night to urinate is a common symptom of BPH that can cause chronic sleep loss and, in turn, lead to fatigue, memory deficits, mood changes including depression, and increased risk of long term medical problems. The nocturia symptom score is a component of the standard AUA BPH Symptom Score used to assess the severity of BPH symptoms and to evaluate BPH treatments.

In the study, subjects received a one-time single dose of NX-1207 administered by intraprostatic injection by a urologist in an office setting. The entire procedure lasted on average 5-10 minutes, with the injection taking 1-2 minutes, and did not require anesthesia or catheterization. There were no significant side effects from NX-1207 in the trial.

Overall, subjects in the study's Intent-to-Treat group who received 2.5 mg of NX-1207 reported a mean improvement in total AUA BPH Symptom Score of 9.71 points after 90 days as compared to the mean improvement of 4.13 points for subjects randomized to finasteride, an approved drug treatment for BPH. This difference was statistically significant (p=0.001). The AUA BPH Symptom Score measures self-assessed severity of BPH symptoms in 7 areas: 1) sensation of incomplete emptying of the bladder; 2) need to urinate frequently; 3) stopping and starting during urination; 4) urgent need to urinate; 5) weakness of urinary stream; 6) need to push or strain during urination; and 7) urination during sleep (nocturia). Published studies of currently approved drugs for BPH show AUA BPH Symptom Score improvement typically in the 3.5 to 5 point range.

The full results from the study will be released at peer-review medical meetings later in 2008.

The Company previously completed three other U.S. trials and 5 follow-up studies for NX-1207. In a Phase 2 double-blind, placebo controlled, randomized multi-center U.S. Study NX02-0014, patients treated with NX-1207 showed after 3 months a statistically significant mean improvement of 9.35 points in BPH Symptom Score values and a statistically significant reduction in mean prostate volume. A recently completed blinded placebo-controlled follow-up study assessed treatment outcomes for 103 subjects from this Phase 2 study 16 to 27 months after a single treatment with NX-1207 or placebo. The study results showed evidence of durable benefit from NX-1207 treatment. At the time of follow-up, 52% of patients treated with NX-1207 were not on BPH medication and had not required surgical intervention for their BPH since their initial treatment with NX-1207; these patients had a mean improvement of 10.2 points in AUA BPH Symptom Score values.

BPH treatment represents a growing market with more than 100 million men worldwide being estimated to suffer from BPH symptoms. The disorder is a common affliction of older men, affecting approximately half of men over age 50 and close to 90% of men by age 80, and is associated with growth in prostate size as men age. BPH causes difficulties with urination associated with aging, such as urination at night, urge to void frequently, hesitancy, weak stream, and other problems, and can cause acute urinary retention requiring immediate medical attention.

More information about Nymox is available at http://www.nymox.com.

This press release contains certain "forward-looking statements" as defined in the United States Private Securities Litigation Reform Act of 1995 that involve a number of risks and uncertainties. There can be no assurance that such statements will prove to be accurate and the actual results and future events could differ materially from management's current expectations. The conduct of clinical trials and the development of drug products involve substantial risks and uncertainties and actual results may differ materially from expectations. Promising early results do not ensure that later stage or larger scale clinical trials will be successful or will proceed as expected. Such factors are detailed from time to time in Nymox's filings with the United States Securities and Exchange Commission and other regulatory authorities.

Multi-Site Study Finds Chemotherapy Break Can Be Recommended For Some Men With Prostate Cancer

2008-02-26T11:45:00.000-08:00

Oregon Health & Science University Cancer Institute researchers, in a first-of-its-kind study, have found that even men with advanced prostate cancer can take a much-needed safe break, or holiday, from chemotherapy.

The double-blind, randomized study, led by principal investigator Tomasz Beer, M.D., recently was published in the journal Cancer. Beer is the Grover C. Bagby Endowed Chair for Cancer Research, director of the OHSU Cancer Institute Prostate Cancer Program, and associate professor of medicine (hematology/medical oncology), OHSU School of Medicine.

Beer and his team wanted to know if men with metastatic, androgen-independent prostate cancer cancer that has spread from the prostate and is not affected by the male hormone, androgen could take a break from docetaxel, an intravenous chemotherapy delivery drug that is the gold standard treatment for androgen-independent prostate cancer. Docetaxel works by killing cancer cells and slowing cell growth. However, the drug also can cause side effects, such as hair loss, nausea, loss of appetite and increased chance for infections. Chemo holidays can be a much-needed vacation from these side effects.

Prior to this study, it wasn't known whether stopping chemotherapy would lead to treatment resistance.

"We wanted to see if we could improve the quality of life for these patients by giving them time away from chemotherapy and possibly extend the time their cancer is controlled. Essentially, what we proved is that in selected subjects, chemotherapy holidays are feasible and provided meaningful breaks from treatment," said Beer.

This is the first multi-institutional trial to examine outcomes from intermittent chemotherapy. A total of 250 men participated. Of those, 18 percent entered the intermittent arm of the study. These men previously had responded well to chemotherapy.

The median duration of the first chemo holiday was 18 weeks. On resumption of chemotherapy, it the majority of subjects responded to treatment. Specifically, 45.5 percent of participants responded with a greater than 50 percent reduction in prostate specific antigen (PSA) from their post-holiday baseline; of those, 45.5 percent had stable PSAs for at least 12 weeks; and 9.1 percent developed disease progression. Prostate-specific antigen is a protein produced by the cells of the prostate gland and is present in small quantities in the serum of healthy men, and it often elevates when prostate cancer is present. Most men have less than 4 nanograms. Anything higher can indicate prostate cancer.

The next step, said Beer, is to study the addition of immunotherapy, treating the cancer by working with the immune system, during the chemotherapy holidays.

"Because we know holidays are a good thing, we want to find ways to make them even longer," Beer said. OHSU and Beer have significant financial interest in Novacea, Inc., a company that has a commercial interest in the results of this research and technology. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.

Positive First-line Phase 1 Safety And Efficacy Data With Picoplatin In Metastatic Prostate Cancer Patients

2008-02-16T08:07:00.001-08:00

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, announced that it is presenting safety and efficacy data in prostate cancer patients from its Phase 1 study of picoplatin, the Company's lead product candidate, at the 2008 Genitourinary (GU) Cancers Symposium, a meeting of the American Society of Clinical Oncology (ASCO) that is being held in San Francisco.

The poster presentation includes safety and efficacy data from a dose-escalating Phase 1 study of picoplatin in combination with full-dose docetaxel (75 mg/m squared) with prednisone as a first-line treatment for metastatic hormone refractory prostate cancer (mHRPC). The Phase 1 study sought to establish the maximum tolerated dose of picoplatin and provide information on the safety and efficacy of picoplatin in combination with docetaxel and prednisone, the standard of care for the first-line treatment of mHRPC.

"The data we have generated with picoplatin in prostate cancer indicate a PSA (prostate specific antigen) response of 65 percent which suggests an improvement compared to docetaxel therapy alone," said Jerry McMahon, Ph.D., chairman and CEO of Poniard Pharmaceuticals. "In addition, the tolerability of picoplatin with full-dose docetaxel supports our ongoing Phase 2 study that we believe will confirm and extend these initial findings. The combination of platinums and taxanes, such as docetaxel, is used to treat many other solid tumors, such as non-small cell and ovarian cancers. We believe that our data support additional evaluation of picoplatin and docetaxel combinations in these cancers in addition to prostate cancer."

In the combination Phase 1 dose-escalating study, 33 patients were treated with one of four doses (60, 80, 100 or 120 mg/m squared) of picoplatin, as well as either 60 mg/m squared or 75 mg/m squared (full-dose) docetaxel plus 5 mg prednisone twice daily. Nine patients received 120 mg/m squared picoplatin and 75 mg/m squared docetaxel every 21 days plus 5 mg prednisone twice daily. This dose, which is also the dose currently under study in the Phase 2 trial, was well tolerated.

Hematological toxicity, including neutropenia, anemia and thrombocytopenia, was dose-dependent and reversible. Neutropenia was the dose-limiting toxicity (DLT). Mild neuropathy (grade 1) was observed in 3 of 33 patients (9 percent) and was unrelated to cumulative picoplatin dose. Neuropathy was infrequent, and no neuropathy of grade 2 or greater was observed. PSA response rate was 65 percent (20 of 31 evaluable patients). Survival data are not yet available. Patient withdrawal from study treatment occurred from death in four patients, progressive disease in eight patients, and withdrawal of consent in one patient. Patients in the Phase 1 trial received a median number of 7 cycles, and 13 of 33 patients completed the maximum of 10 cycles of treatment according to the study protocol.

Based on safety and efficacy data from the Phase 1 study, the recommended Phase 2 regimen of intravenous picoplatin (120 mg/m squared) and docetaxel (75 mg/m squared) every 21 days with prednisone (5 mg) orally twice daily is being evaluated in a Phase 2 study in chemotherapy naive mHRPC patients. PSA response is the primary endpoint; secondary endpoints include radiological response using RECIST criteria, time to progression and survival (1-year, progression-free and overall). The Phase 2 trial completed enrollment in December 2007. The Company expects to present the results of this study in scientific forums later this year.

About Picoplatin

Picoplatin is an intravenous chemotherapeutic agent that has an improved safety profile compared to existing platinum-based chemotherapeutics. It was designed to overcome platinum resistance associated with the treatment of solid tumors. Picoplatin has been evaluated in more than 800 patients and has demonstrated activity in multiple indications with no evidence of significant kidney, nerve toxicity or hearing loss, toxicities commonly observed with other platinum chemotherapy drugs.

In addition to the Phase 2 clinical trial in patients with mHRPC, Poniard is evaluating intravenous picoplatin in an ongoing pivotal Phase 3 trial, known as SPEAR (Study of Picoplatin Efficacy After Relapse), in small cell lung cancer. This registrational trial is being conducted under a Special Protocol Assessment from the U.S. Food and Drug Administration and is evaluating overall survival as the primary endpoint. The Company also is evaluating intravenous picoplatin in an ongoing Phase 2 clinical trial for the treatment of colorectal cancer. Oral picoplatin is being evaluated in a Phase 1 clinical trial in solid tumors.

About Poniard Pharmaceuticals

Poniard Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative oncology products to impact the lives of people with cancer. Picoplatin, the Company's lead platform product candidate, is a new generation platinum therapy with an improved safety profile. Picoplatin is designed to overcome and prevent platinum resistance associated with chemotherapy in solid tumors, and is being studied in multiple cancer indications, combinations and formulations. Clinical trials of intravenous picoplatin include a Phase 3 trial in small cell lung cancer and Phase 2 trials in metastatic colorectal and hormone-refractory prostate cancer, as well as a clinical trial of oral picoplatin in solid tumors. Picoplatin has not been approved by regulatory authority for use in humans. For additional information please visit http://www.poniard.com.

This release contains forward-looking statements, including statements regarding the Company's business objectives and strategic goals, drug development plans, results of clinical trials and the potential safety and efficacy of its products in development. The Company's actual results may differ materially from those indicated in these forward-looking statements based on a number of factors, including risks and uncertainties associated with the Company's research and development activities; the results of pre-clinical and clinical testing; the receipt and timing of required regulatory approvals; the market's acceptance of the Company's proposed products; the Company's anticipated operating losses, need for future capital and ability to obtain future funding; competition from third parties; the Company's ability to preserve and protect intellectual property rights; the Company's dependence on third-party manufacturers and suppliers; the Company's lack of sales and marketing experience; the Company's ability to attract and retain key personnel; changes in technology, government regulation and general market conditions; and the risks and uncertainties described in the Company's current and periodic reports filed with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K for the year ended December 31, 2006, as amended, and most current Quarterly Report on Form 10-Q. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to update any forward-looking statement to reflect new information, events or circumstances after the date of this release or to reflect the occurrence of unanticipated events.

Cell Genesys Reports Association Between Immune Response And Patient Survival In Phase 2 Trial Of GVAX Immunotherapy For Prostate Cancer

2008-02-16T08:05:00.000-08:00

Cell Genesys, Inc. (Nasdaq: CEGE) reports the results of an analysis examining the potential association between immune responses to GVAX immunotherapy for prostate cancer and increased patient survival in a Phase 2 trial in patients with metastatic, hormone refractory prostate cancer (HRPC). More than 400 patient-specific GVAX-induced antibody responses were identified in the sera of the treated patients by three different biochemical techniques confirming, as previously reported, that GVAX treatment results in a broad, multi-antigen immune response. An ongoing analysis of these GVAX-induced antibody responses has shown that at least two of the antibody responses are associated with patient survival, an association that is independent of the dose and number of treatments administered. These data will be presented today by Dr. Thomas Harding and colleagues from Cell Genesys at the American Society of Clinical Oncology's Genitourinary Cancer Symposium being held in San Francisco, California.

Cell Genesys has previously reported the results of two multicenter Phase 2 trials of GVAX immunotherapy for prostate cancer in metastatic HRPC. The second of these two trials enrolled 80 patients. The serum of 65 patients (the total number for whom adequate sera were available) were examined to determine each patient's immune response to two specific antigens, HLA-A24 and FLJ14668, following GVAX treatment. Thirty-four of 65 patients demonstrated an FLJ14668-specific antibody immune response. These 34 patients had a median survival of 43 months, compared to a median survival of 21 months achieved by the patients who did not generate anti-FLJ14668 antibodies (p=0.002). Twenty-two of these 65 patients received a dose of GVAX immunotherapy for prostate cancer comparable to that being evaluated in ongoing Phase 3 clinical trials. Of these 22 patients, 16 patients (73 percent) mounted an immune response to FLJ14668. These 16 patients achieved a median survival of 44.9 months. As previously reported, the median survival for all 22 patients in this treatment group was 35.0 months. Finally, of the 58 patients who were HLA-A24 genotype negative and therefore potentially able to mount anti-HLA-A24 specific antibody responses, 30 patients were found to be anti-HLA-A24 antibody positive. These 30 patients had a median survival of 43 months, compared to a median survival of 18 months in the patients who did not generate anti-HLA-A24 antibodies (p=0.05). Importantly, the apparent associations between the presence of these two specific antibody responses and survival were shown by multivariate analysis to be independent of both dose and duration of treatment.

"The findings being reported today indicate a potential association between two specific GVAX-induced antibody responses and patient survival, an association consistent with the proposed mechanism of action for this product. We look forward to expanding these findings in a prospective analysis of the sera of patients treated in our two randomized controlled Phase 3 trials," stated Peter K. Working, Ph.D., senior vice president of research and development at Cell Genesys. "Since GVAX immunotherapy for prostate cancer is a multi-antigen product that can induce a broad immune response, we believe we have a unique opportunity to identify the widest possible array of specific antibody responses that may be associated with clinical benefit."

Cell Genesys is currently evaluating GVAX immunotherapy for prostate cancer in two Phase 3 multicenter, randomized, controlled clinical trials. VITAL-1, which is fully enrolled with 626 patients, is designed to compare GVAX cancer immunotherapy to Taxotere(R) (docetaxel) chemotherapy plus prednisone in HRPC patients with metastatic disease who are asymptomatic with respect to cancer-related pain. The primary endpoint of the trial is an improvement in survival. An interim analysis of the trial was recently conducted by an independent data monitoring committee in the timeframe originally estimated and resulted in the recommendation to continue the trial. The company expects to have enough events to trigger the final analysis of VITAL-1 in the second half of 2009. VITAL-2, which the company expects to fully enroll with approximately 600 patients in the first half of 2009, is designed to evaluate the safety and efficacy of GVAX immunotherapy for prostate cancer used in combination with Taxotere chemotherapy compared to the use of Taxotere chemotherapy and prednisone in HRPC patients with metastatic disease who are symptomatic with cancer-related pain. The primary endpoint of the trial is also an improvement in survival. The company expects to have enough events to trigger an interim analysis of VITAL-2 in the first half of 2009.

About GVAX Cancer Immunotherapies

GVAX cancer immunotherapies are non patient-specific investigational products comprised of whole tumor cells that have been modified to secrete GM- CSF (granulocyte-macrophagecolony-stimulating factor), an immune stimulatory cytokine, and then irradiated for safety. GVAX is administered via intradermal injections on an outpatient basis. To date, over 600 patients have been treated with GVAX cancer immunotherapies in Phase 1 and Phase 2 clinical trials for multiple indications, including prostate cancer, pancreatic cancer, and leukemia. The company is currently manufacturing GVAX immunotherapy for prostate cancer in its bioreactor-based manufacturing plant in Hayward, California, a facility that is also capable of manufacturing the product for commercialization.

About Cell Genesys

ASCO GU 2008 - Androgen Suppression And Radiation Versus Radiation For Prostate Cancer

2008-02-16T07:40:00.000-08:00

UroToday.com - This study sought to compare survival in a prospective randomized trial of radiotherapy (XRT) alone vs. XRT with 6 months of ADT. 206 men were accrued and randomized. They all had at least one unfavorable-risk factor. 70 Gy of XRT was given. The lymph nodes were not treated. ADT was 2 months prior, during and 2 months after XRT. Salvage ADT was given for a PSA >10ng/ml. The study compliance was very high, but 29% had the antiandrogen held primarily due to hepatic or GI toxicity. The median PSA was 11ng/ml and 73% had Gleason 7 or higher. Thus it is a mix of intermediate and high-risk patients.

The PCSM difference was 10%, favoring combined therapy. Overall survival was favored by 13%. Most patients in the study had only mild comorbidity. A history of MI was the reason for moderate or severe comorbidity in 25%. At 8 years, there is a 26% overall survival benefit if the patient had only mild comorbidities. In moderate or severe comorbidities, there was a worse overall survival by 29% if they received XRT and ADT. This surprising result suggests that sicker patients had interaction of ADT with their existing comorbidities (such as coronary artery disease) to result in worse survival. He suggested that future studies should include a pre-treatment comorbidity randomization strategy.

Presented by A. V. D'Amico at the American Society of Clinical Oncology (ASCO) - 2008 Genitourinary Cancers Symposium - A Multidisciplinary Approach - February 14-16, 2008 San Francisco, California, USA

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA

Researchers Develop Successful Test Vaccine That Prevents Development Of Prostate Cancer

2008-02-04T03:34:00.000-08:00

Researchers at the University of Southern California have developed a prostate cancer vaccine that prevented the development of cancer in 90 percent of young mice genetically predestined to develop the disease. In the February 1 issue of Cancer Research, they suggest the same strategy might work for men with rising levels of PSA (prostate specific antigen), a potential diagnostic indicator of prostate cancer

"By early vaccination, we have basically given these mice life-long protection against a disease they were destined to have," said the study's lead investigator, W. Martin Kast, Ph.D., a professor of Molecular Microbiology & Immunology and Obstetrics & Gynecology at the Norris Comprehensive Cancer Center. "This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer."

Now, men with rising PSA levels but no other signs of cancer are advised "watchful waiting" - no treatment until signs of the cancer appear, Kast says. "But what if instead of a watchful wait, we vaccinate? That could change the course of the disease."

The study findings also represent a new way to think about the use of therapeutic prostate cancer vaccines, Kast says. Vaccines now in testing are designed to treat men whose cancers are advanced and unresponsive to therapy, and results have offered limited clinical benefit, he says. This novel approach targets the precancerous state with the aim of preventing cancer from developing, he says.

The Kast team's preventive vaccine is designed to mount an immune response against prostate stem cell antigen (PSCA), the protein target of some therapeutic vaccines under development. PSCA, a membrane protein, is over-expressed in about one-third of early-stage prostate cancers, but expression ramps up in all prostate tumors as they grow and advance. PSCA is also expressed at low-levels in normal prostate gland tissue as well as in the bladder, colon, kidney and stomach.

The researchers created a prime-boost vaccination scheme using two kinds of vaccines and tested it in 8-week-old mice that were genetically altered to develop prostate cancer later in life. The first vaccine simply delivered a fragment of DNA that coded for PSCA, thus producing an influx of PSCA protein to alert the immune system. The booster shot, given two weeks later, used a modified horse virus to deliver the PSCA gene.

"Confronting the immune system in two different ways forces it to mount a strong response," Kast said.

In the experimental group, two of 20 mice developed prostate cancer at the end of one year, and by contrast, all control mice had died of the disease. Researchers found that mice in the experimental group had all developed very small tumors that did not progress. "There were tiny nodules of prostate cancer in the mice that were surrounded by an army of immune system cells," Kast said. "The vaccination turned the cancer into a chronic, manageable disease."

The vaccination strategy also works with other antigens, Kast says. The researchers recently tried another prostate cancer membrane target and found that after 1.5 years, 65 percent of experimental mice were still alive, and of those that died, the suspected cause was old age.

Crucially, investigators further found that treated mice did not develop autoimmune disease, a side effect that could develop if the vaccine had also targeted PSCA expression in normal cells. "Theoretically, the vaccine could produce a response in any tissue that expresses the antigen, but the fact that PSCA is expressed in such low levels in normal tissue may prevent that complication," he said.

Still, studies in humans are needed to ensure autoimmunity does not develop, Kast says.

"We feel this is a very promising approach," he said. "With just two shots, the vaccine will prime immune cells to be on the lookout for any cell that over-expresses PSCA."

The study was funded by a pre-doctoral training grant from the National Institutes of Health and a grant from the Margaret E. Early Medical Research Trust. Co-authors include researchers from the University of Southern California as well as from AlphaVax, inc., of Research Triangle Park, North Carolina.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants.

The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.