Ignite Creation Date:
2024-05-05 @ 5:14 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00411853
Status:
UNKNOWN
Last Update Posted:
2009-07-31
First Post:
2006-12-14
Brief Title:
Efficacy of FWGE in Combination With Hormone Therapy for the Treatment of Hormone-Refractory Prostate Cancer Patients
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
An Open Phase II Clinical Trial of Fermented Wheat Germ Extract in Combination With Hormone Therapy for the Treatment of Hormone-Refractory Prostate Cancer Patients
Status:
UNKNOWN
Status Verified Date:
2009-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We propose in this study to treat hormone refractory prostate cancer HRPC patients with a novel preparation of fermented wheat germ nutriment FWGE in combination with the 1st line hormone therapy the gonadotropin releasing hormone GnRH which stopped being effective The study will be conducted during two years with 60 patients The efficacy will be assessed in terms of clinical and serological response and by specific questionnaires
This concept is based on previous reports regarding other diseases such as colon cancer where the addition of a new drug to a drug which previously had failed improved the patients survival the quality of life and the clinical parameters In addition preclinical data have shown activity of that regimen in prostate cancer cell lines and in animals models
FWGE exhibits a wide variety of mode of actions in a wide range of malignant tumors It increased the natural immune responses while decreasing the systemic inflammation often present in cancer patients It reduced the growth of human prostate tumor xenograft in mice and prolonged their survival It delayed disease progression increased overall survivals improve quality of life and reduce oxidative stress
The long-term goal of this research is that the addition of FWGE to a drug which previously had failed would slow down disease progression in patients with advanced and thus refractory cancers improving the patients quality of life their clinical parameters and survival
This concept is based on previous reports regarding other diseases such as colon cancer where the addition of a new drug to a drug which previously had failed improved the patients survival the quality of life and the clinical parameters In addition preclinical data have shown activity of that regimen in prostate cancer cell lines and in animals models
FWGE exhibits a wide variety of mode of actions in a wide range of malignant tumors It increased the natural immune responses while decreasing the systemic inflammation often present in cancer patients It reduced the growth of human prostate tumor xenograft in mice and prolonged their survival It delayed disease progression increased overall survivals improve quality of life and reduce oxidative stress
The long-term goal of this research is that the addition of FWGE to a drug which previously had failed would slow down disease progression in patients with advanced and thus refractory cancers improving the patients quality of life their clinical parameters and survival
Detailed Description:
Background and Significance
1 The challenge
Prostate cancer is a major worldwide health problem and is the most frequently diagnosed malignancy in men today In the United States prostate cancer is the most common malignancy found in men accounting for more than 29 of all diagnosed cancer and approximately 13 of all cancer deaths Nearly one in six men will be diagnosed with the disease at some time in their lives In 2003 alone an estimated 221000 men in the United States were diagnosed with prostate cancer In 1999 37000 deaths were attributed to prostate cancer in the United States and in 2003 more than 28000 died of the disease Hormone-refractory prostate cancer HRPC is one of the most aggressive cancers It is the second ranking cause of cancer-related deaths Patients with localized disease have the option of radiation therapy or radical prostatectomy as definitive treatment modalities for curing the disease However the cancer recurs in its metastatic form in 20-30 of these patients In addition approximately 10 of patients diagnosed with the disease already have distant metastases making localized therapy irrelevant The primary treatment for the advanced state of prostate cancer is androgen deprivation therapy to inhibit the testosterone production that facilitates prostate tumor growth Androgen deprivation therapy is administered either by surgical castration or by medications that block testosterone production While this treatment is effective in 85-95 of patients the response time lasts approximately for 12 -24 months after which the cancer progresses to its androgen-insensitive stage The androgen independent prostate cancer cells progress to metastatic disease Limited treatment options exist for the hormone refractory prostate cancer HRPC patient and median survival time rarely exceeds one year
Once androgen independence has occurred conventional chemotherapy for the treatment of metastatic cancer has shown limited activity in patients in addition to causing toxic side effects While new chemotherapeutic regimens and hormonal agents are being tested the survival and quality of life of these HRPC patients remains low
2 The innovation
We propose to treat progressing HRPC patients with a novel combination of 1st line of hormone therapy GnRH analogues with the non-toxic dietary supplement fermented wheat germ nutriment FWGE This suggestion is based on preclinical data showing activity of the regimen in prostate cancer cell lines and in animal models Furthermore there are previous reports regarding other diseases such as colon cancer where the addition of a new treatment to a therapy which had previously failed improved patient survival quality of life and the clinical parameters
The characteristics of Fermented wheat germ extract FWGE Fermented wheat germ extract with a standardized complex mixture of molecules is termed FWGE The product is manufactured under GMP conditions and is available as a water-soluble granulate which administered orally
The compound is approved as a medical food for cancer patients It has been recently classified in the US as GRAS Generally Recognized as Safe and is used for complementing the standard anticancer treatments
The molecular targets of FWGE include poly ADP-ribose polymerase PARP major histocompatibility complex MHC class I transketolase TK ribonucleotide reductase RNR and intracellular adhesion molecule ICAM 1 By activating the caspase-3 downstream proteases FWGE treatment results in cleavage of PARP thus preventing DNA repair in cancer cells
FWGE treatment decreases major histocompatibility complex class I MHC-I in cancer cells MHC-I down regulation in cancer cells leads to an increased natural killer NK cells activity NK cells are considered as the first line of anticancer immune defense
TK is the key enzyme of the reductive pentose cycle In cancer cells this cycle is responsible for supplying these cells increased need for ribose molecules necessary for synthesis the sugar chains of the nucleic acids RNR enzymes which are strongly inhibited by FWGE catalyze the synthesis of the DNA components
It has been known that a tumor can not grow bigger than 2 mm in diameter except if it is able to synthesize its own blood vessels angiogenesis process The blood vessels in tumors lack the protein ICAM-1 which is responsible for facilitating the transfer of anticancer immune cells e g macrophages via the vessels walls into the tumor FWGE treatment increases the synthesis of ICAM-1
In addition FWGE has a wide therapeutic window In order to observe any toxicity effects on normal cells more than 50 times higher dosage of FWGE than the recommended one for therapy is needed This very positive toxicity profile gives a wide therapeutic window for the applicability of this product
Recently it has also been shown that FWGE is a strong but non-selective inhibitor of the cyclooxygenases 1 and 2 thus this preparation has an anti-inflammatory activity
The preparation has also been shown to induce apoptosis in gastric carcinoma cells
Advantages of FWGE
The FWGE preparation is non-toxic and safe This serves as a major consideration in its selection for the treatment of advanced cancer patients who suffer from low performance status and consequently have a poor quality of life
FWGE is orally administrated
The FWGE preparation exhibits a wide variety of mode of actions in a wide range of malignant tumors
The product is able to increase the natural immune responses while decreasing the systemic inflammation often present in the patients
It is anticipated that FWGE by complementing therapeutic efficacy of the standard hormonal anticancer treatments could suppress disease progression thus prolonging patients survival and improving quality of life parameters
1 The challenge
Prostate cancer is a major worldwide health problem and is the most frequently diagnosed malignancy in men today In the United States prostate cancer is the most common malignancy found in men accounting for more than 29 of all diagnosed cancer and approximately 13 of all cancer deaths Nearly one in six men will be diagnosed with the disease at some time in their lives In 2003 alone an estimated 221000 men in the United States were diagnosed with prostate cancer In 1999 37000 deaths were attributed to prostate cancer in the United States and in 2003 more than 28000 died of the disease Hormone-refractory prostate cancer HRPC is one of the most aggressive cancers It is the second ranking cause of cancer-related deaths Patients with localized disease have the option of radiation therapy or radical prostatectomy as definitive treatment modalities for curing the disease However the cancer recurs in its metastatic form in 20-30 of these patients In addition approximately 10 of patients diagnosed with the disease already have distant metastases making localized therapy irrelevant The primary treatment for the advanced state of prostate cancer is androgen deprivation therapy to inhibit the testosterone production that facilitates prostate tumor growth Androgen deprivation therapy is administered either by surgical castration or by medications that block testosterone production While this treatment is effective in 85-95 of patients the response time lasts approximately for 12 -24 months after which the cancer progresses to its androgen-insensitive stage The androgen independent prostate cancer cells progress to metastatic disease Limited treatment options exist for the hormone refractory prostate cancer HRPC patient and median survival time rarely exceeds one year
Once androgen independence has occurred conventional chemotherapy for the treatment of metastatic cancer has shown limited activity in patients in addition to causing toxic side effects While new chemotherapeutic regimens and hormonal agents are being tested the survival and quality of life of these HRPC patients remains low
2 The innovation
We propose to treat progressing HRPC patients with a novel combination of 1st line of hormone therapy GnRH analogues with the non-toxic dietary supplement fermented wheat germ nutriment FWGE This suggestion is based on preclinical data showing activity of the regimen in prostate cancer cell lines and in animal models Furthermore there are previous reports regarding other diseases such as colon cancer where the addition of a new treatment to a therapy which had previously failed improved patient survival quality of life and the clinical parameters
The characteristics of Fermented wheat germ extract FWGE Fermented wheat germ extract with a standardized complex mixture of molecules is termed FWGE The product is manufactured under GMP conditions and is available as a water-soluble granulate which administered orally
The compound is approved as a medical food for cancer patients It has been recently classified in the US as GRAS Generally Recognized as Safe and is used for complementing the standard anticancer treatments
The molecular targets of FWGE include poly ADP-ribose polymerase PARP major histocompatibility complex MHC class I transketolase TK ribonucleotide reductase RNR and intracellular adhesion molecule ICAM 1 By activating the caspase-3 downstream proteases FWGE treatment results in cleavage of PARP thus preventing DNA repair in cancer cells
FWGE treatment decreases major histocompatibility complex class I MHC-I in cancer cells MHC-I down regulation in cancer cells leads to an increased natural killer NK cells activity NK cells are considered as the first line of anticancer immune defense
TK is the key enzyme of the reductive pentose cycle In cancer cells this cycle is responsible for supplying these cells increased need for ribose molecules necessary for synthesis the sugar chains of the nucleic acids RNR enzymes which are strongly inhibited by FWGE catalyze the synthesis of the DNA components
It has been known that a tumor can not grow bigger than 2 mm in diameter except if it is able to synthesize its own blood vessels angiogenesis process The blood vessels in tumors lack the protein ICAM-1 which is responsible for facilitating the transfer of anticancer immune cells e g macrophages via the vessels walls into the tumor FWGE treatment increases the synthesis of ICAM-1
In addition FWGE has a wide therapeutic window In order to observe any toxicity effects on normal cells more than 50 times higher dosage of FWGE than the recommended one for therapy is needed This very positive toxicity profile gives a wide therapeutic window for the applicability of this product
Recently it has also been shown that FWGE is a strong but non-selective inhibitor of the cyclooxygenases 1 and 2 thus this preparation has an anti-inflammatory activity
The preparation has also been shown to induce apoptosis in gastric carcinoma cells
Advantages of FWGE
The FWGE preparation is non-toxic and safe This serves as a major consideration in its selection for the treatment of advanced cancer patients who suffer from low performance status and consequently have a poor quality of life
FWGE is orally administrated
The FWGE preparation exhibits a wide variety of mode of actions in a wide range of malignant tumors
The product is able to increase the natural immune responses while decreasing the systemic inflammation often present in the patients
It is anticipated that FWGE by complementing therapeutic efficacy of the standard hormonal anticancer treatments could suppress disease progression thus prolonging patients survival and improving quality of life parameters
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None