Thema: Presse: Xcytrin In Patients with Brain Metastases
Presse: Xcytrin In Patients with Brain Metastases
Tilo
11.10.2002 13:06:33
Pharmacyclics (PCYC) Announces Complete Results From Xcytrin Phase 3 Clinical Trial Presented At 44th Annual ASTRO Meeting
Phase 3 SMART Trial to Begin This Quarter to Confirm Benefits of Xcytrin In Non-Small Cell Lung Cancer Patients with Brain Metastases
Oct. 8, 2002
Pharmacyclics, Inc. today announced that researchers presented complete results from its first Phase 3 clinical trial of Xcytrin(R) (motexafin gadolinium) Injection for the potential treatment of brain metastases in an oral presentation at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO). Researchers also described the company´s second Phase 3 trial, called the SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial, which is expected to begin enrolling patients by the end of this quarter.
Researchers concluded that Xcytrin, when added to whole brain radiation therapy (WBRT), significantly prolongs the time to neurologic progression and, as assessed by the clinical investigators, decreases deaths due to brain tumor (CNS) progression in patients with brain metastases from lung cancer.
"The results of this trial, which is probably the most comprehensive randomized controlled trial ever reported in brain metastases, provide evidence of the potential benefits of Xcytrin for patients with this devastating disease, particularly those with lung cancer," said Minesh Mehta, M.D., professor and chairman, Department of Human Oncology, University of Wisconsin Medical School, who presented the data. "We look forward to applying all we have learned from this trial to expedite the SMART trial, which is specifically designed to confirm the benefits observed in the first trial, particularly controlling CNS disease progression, which can have devastating effects on the patients and their caregivers."
Trial Design and Results
This Phase 3 international randomized controlled study compared Xcytrin plus WBRT to WBRT alone. 401 patients with brain metastases (i.e., cancer that has spread to the brain from another part of the body) from solid tumors were enrolled in the study at over 50 leading medical centers in the United States, Canada and Europe.
In addition to measuring survival, the study incorporated comprehensive assessments of neurologic and neurocognitive function. Despite the use of WBRT, most patients experience neurologic progression indicating the need for improved therapies that better control tumor growth in the brain. This study utilized two methods for assessment of neurologic function: standard clinical assessment by the clinical investigators and assessment by an independent events review committee (ERC) that was blinded to treatment assignment, which meant they did not know which patients received Xcytrin.
The clinical results from both the investigator and ERC assessments were in agreement, particularly in patients with non-small cell lung cancer, the largest group of patients in the trial (n = 251). Treatment with Xcytrin in this patient population was associated with improvement in time to neurologic and neurocognitive progression.
In the intent-to-treat, 401-patient population, there was a significant improvement in time to neurologic progression seen in patients receiving Xcytrin as determined by investigator assessment. Median time to neurologic progression was 3.8 months with WBRT alone versus 4.3 months with Xcytrin plus WBRT (p = 0.018). Most of this benefit was seen in the lung cancer patients with a median time to neurologic progression in this group of 3.7 months with WBRT alone versus 5.5 months with Xcytrin plus WBRT (p = 0.025). ERC- determined time to neurologic progression showed a benefit with Xcytrin treatment in lung cancer patients. In this assessment, median time to neurologic progression was 7.4 months in lung cancer patients receiving WBRT alone. A median time to neurologic progression was not reached (less than 50% of patients progressed) by the end of the study observation period of 12 months in lung cancer patients treated with WBRT plus Xcytrin (p = 0.048).
There was also a significant reduction in CNS deaths in lung cancer patients receiving Xcytrin as assessed by the clinical investigators. 51.5% of lung cancer patients receiving WBRT alone died from progression of their brain tumors versus 35.2% of patients receiving WBRT plus Xcytrin (p=0.02), a 33% reduction in CNS death rate.
These results were consistent with neurocognitive testing -- a secondary endpoint that measures ability to think -- which revealed a benefit in prolonging time to neurocognitive progression for lung cancer patients treated with Xcytrin (p = 0.063).
Xcytrin was well tolerated with the most commonly observed side effects being skin and urine discoloration, hypertension and nausea.
The SMART Trial
Based on the promising activity observed in this trial, Pharmacyclics, together with leading experts in radiation and medical oncology, has designed the SMART trial incorporating important information learned from the initial trial. The trial is designed to enroll 550 patients with brain metastases from non-small cell lung cancer and will compare the effects of WBRT alone to those of WBRT plus Xcytrin. The primary efficacy endpoint will be time to neurologic progression. Survival and neurocognitive function will also be assessed as secondary endpoints of the trial.
"We are able to optimize the design and conduct of our second Phase 3 trial in patients with lung cancer based on the randomized controlled data obtained from the first trial," said Markus F. Renschler, M.D., vice president of oncology clinical development at Pharmacyclics. "The FDA has reviewed the trial design and has indicated that time to neurologic progression is an approvable efficacy endpoint. We are selecting patients most likely to benefit from treatment and have streamlined and improved the neurologic and neurocognitive assessments. In addition, we are planning to work with many of the highest enrolling clinical sites from the previous trial to facilitate expeditious enrollment. We have a high degree of confidence in our second Phase 3 trial based on the data from our first trial indicating Xcytrin´s novel anti-cancer activity, and on our knowledge and experience."
About Xcytrin
Xcytrin, the first of a new class of drugs called texaphyrins, selectively accumulates in cancer cells based on their unique biochemical features and disrupts cellular metabolism. By interfering with the flow of energy, Xcytrin prevents cancer cells from repairing damage caused by the effects of radiation and chemotherapy without increasing damage to normal tissue. Xcytrin is paramagnetic, and when localized in cancer cells, produces an enhancement of the MRI signal, which can be used to image the tumor.
About Brain Metastases
Brain metastases is one of the most common conditions treated with radiation therapy. There are about 150,000 to 170,000 cases per year and the incidence is increasing. The most common cause of brain metastases is lung cancer, affecting up to 90,000 patients. Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in most cases, death. Patients with brain metastases usually suffer serious deterioration of neurologic and neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.
About Pharmacyclics
Pharmacyclics is a pharmaceutical company developing products to improve upon current therapeutic approaches to cancer and atherosclerosis. The company´s products are rationally designed, ring-shaped small molecules called texaphyrins that disrupt the bioenergetic processes of diseased cells, such as cancer and atherosclerotic plaque. When activated by various forms of energy, including X-ray and light, these texaphyrins can help to reduce or eliminate the diseased tissue.
Phase 3 SMART Trial to Begin This Quarter to Confirm Benefits of Xcytrin In Non-Small Cell Lung Cancer Patients with Brain Metastases
Oct. 8, 2002
Pharmacyclics, Inc. today announced that researchers presented complete results from its first Phase 3 clinical trial of Xcytrin(R) (motexafin gadolinium) Injection for the potential treatment of brain metastases in an oral presentation at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO). Researchers also described the company´s second Phase 3 trial, called the SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial, which is expected to begin enrolling patients by the end of this quarter.
Researchers concluded that Xcytrin, when added to whole brain radiation therapy (WBRT), significantly prolongs the time to neurologic progression and, as assessed by the clinical investigators, decreases deaths due to brain tumor (CNS) progression in patients with brain metastases from lung cancer.
"The results of this trial, which is probably the most comprehensive randomized controlled trial ever reported in brain metastases, provide evidence of the potential benefits of Xcytrin for patients with this devastating disease, particularly those with lung cancer," said Minesh Mehta, M.D., professor and chairman, Department of Human Oncology, University of Wisconsin Medical School, who presented the data. "We look forward to applying all we have learned from this trial to expedite the SMART trial, which is specifically designed to confirm the benefits observed in the first trial, particularly controlling CNS disease progression, which can have devastating effects on the patients and their caregivers."
Trial Design and Results
This Phase 3 international randomized controlled study compared Xcytrin plus WBRT to WBRT alone. 401 patients with brain metastases (i.e., cancer that has spread to the brain from another part of the body) from solid tumors were enrolled in the study at over 50 leading medical centers in the United States, Canada and Europe.
In addition to measuring survival, the study incorporated comprehensive assessments of neurologic and neurocognitive function. Despite the use of WBRT, most patients experience neurologic progression indicating the need for improved therapies that better control tumor growth in the brain. This study utilized two methods for assessment of neurologic function: standard clinical assessment by the clinical investigators and assessment by an independent events review committee (ERC) that was blinded to treatment assignment, which meant they did not know which patients received Xcytrin.
The clinical results from both the investigator and ERC assessments were in agreement, particularly in patients with non-small cell lung cancer, the largest group of patients in the trial (n = 251). Treatment with Xcytrin in this patient population was associated with improvement in time to neurologic and neurocognitive progression.
In the intent-to-treat, 401-patient population, there was a significant improvement in time to neurologic progression seen in patients receiving Xcytrin as determined by investigator assessment. Median time to neurologic progression was 3.8 months with WBRT alone versus 4.3 months with Xcytrin plus WBRT (p = 0.018). Most of this benefit was seen in the lung cancer patients with a median time to neurologic progression in this group of 3.7 months with WBRT alone versus 5.5 months with Xcytrin plus WBRT (p = 0.025). ERC- determined time to neurologic progression showed a benefit with Xcytrin treatment in lung cancer patients. In this assessment, median time to neurologic progression was 7.4 months in lung cancer patients receiving WBRT alone. A median time to neurologic progression was not reached (less than 50% of patients progressed) by the end of the study observation period of 12 months in lung cancer patients treated with WBRT plus Xcytrin (p = 0.048).
There was also a significant reduction in CNS deaths in lung cancer patients receiving Xcytrin as assessed by the clinical investigators. 51.5% of lung cancer patients receiving WBRT alone died from progression of their brain tumors versus 35.2% of patients receiving WBRT plus Xcytrin (p=0.02), a 33% reduction in CNS death rate.
These results were consistent with neurocognitive testing -- a secondary endpoint that measures ability to think -- which revealed a benefit in prolonging time to neurocognitive progression for lung cancer patients treated with Xcytrin (p = 0.063).
Xcytrin was well tolerated with the most commonly observed side effects being skin and urine discoloration, hypertension and nausea.
The SMART Trial
Based on the promising activity observed in this trial, Pharmacyclics, together with leading experts in radiation and medical oncology, has designed the SMART trial incorporating important information learned from the initial trial. The trial is designed to enroll 550 patients with brain metastases from non-small cell lung cancer and will compare the effects of WBRT alone to those of WBRT plus Xcytrin. The primary efficacy endpoint will be time to neurologic progression. Survival and neurocognitive function will also be assessed as secondary endpoints of the trial.
"We are able to optimize the design and conduct of our second Phase 3 trial in patients with lung cancer based on the randomized controlled data obtained from the first trial," said Markus F. Renschler, M.D., vice president of oncology clinical development at Pharmacyclics. "The FDA has reviewed the trial design and has indicated that time to neurologic progression is an approvable efficacy endpoint. We are selecting patients most likely to benefit from treatment and have streamlined and improved the neurologic and neurocognitive assessments. In addition, we are planning to work with many of the highest enrolling clinical sites from the previous trial to facilitate expeditious enrollment. We have a high degree of confidence in our second Phase 3 trial based on the data from our first trial indicating Xcytrin´s novel anti-cancer activity, and on our knowledge and experience."
About Xcytrin
Xcytrin, the first of a new class of drugs called texaphyrins, selectively accumulates in cancer cells based on their unique biochemical features and disrupts cellular metabolism. By interfering with the flow of energy, Xcytrin prevents cancer cells from repairing damage caused by the effects of radiation and chemotherapy without increasing damage to normal tissue. Xcytrin is paramagnetic, and when localized in cancer cells, produces an enhancement of the MRI signal, which can be used to image the tumor.
About Brain Metastases
Brain metastases is one of the most common conditions treated with radiation therapy. There are about 150,000 to 170,000 cases per year and the incidence is increasing. The most common cause of brain metastases is lung cancer, affecting up to 90,000 patients. Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in most cases, death. Patients with brain metastases usually suffer serious deterioration of neurologic and neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.
About Pharmacyclics
Pharmacyclics is a pharmaceutical company developing products to improve upon current therapeutic approaches to cancer and atherosclerosis. The company´s products are rationally designed, ring-shaped small molecules called texaphyrins that disrupt the bioenergetic processes of diseased cells, such as cancer and atherosclerotic plaque. When activated by various forms of energy, including X-ray and light, these texaphyrins can help to reduce or eliminate the diseased tissue.
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