Cowden's DiseasePhase 2NCT00971789
Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes
A Phase 2 study testing fludeoxyglucose F 18, sirolimus and Clinical Videography in people with Cowden's Disease and Hamartoma Syndrome, Multiple, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: People with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) hamartomatous tumor syndromes (PHTS) have a mutation in one of their genes called PTEN that can lead to benign tumors called hamartomas throughout the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cowden's Disease, Hamartoma Syndrome, Multiple
- What is being tested?
- fludeoxyglucose F 18, sirolimus and Clinical Videography
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Oct 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or lactating women, due to potentially harmful effects of sirolimus on the embryo or fetus or nursing child.
- Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.
- Patients taking immuno-suppressive agents other than prescribed corticosteroids, which must not exceed the equivalent of 20 mg/d of prednisone.
- Patients that are on the following cytochrome P450 3A4 (CYP3A4) inhibitors and cannot replace these medications with other equivalent medications for the period of the study: protease inhibitors, cyclosporine, fluconazole, itraconazole, ketoconazole, metoclopramide, felodipine, nifedipine, carbamazepine, Phenobarbital, grapefruit juice, and St. John's Wort.
- Patients who have received live vaccines in the past 30 days.
- Patients with human immunodeficiency virus (HIV) seropositivity, due to potential drug interactions between sirolimus and anti-retroviral medications, as well as the unknown effects of single agent sirolimus on the immune system in HIV patients.
Show all 11Show fewer
- Patients with interstitial lung disease or pneumonitis.
- Patients with bleeding diathesis.
- Patients with prior or active pneumocystis jirovecii (PJP) pneumonia.
- Patients with prior use of rapamycin, a rapamycin analogue, or other mTOR inhibitor.
- Patients who do not agree to have multiple repeated biopsies performed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Study of Sirolimus (Rapamycin, Rapamune[Registered Trademark]) in Subjects With Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN
Background:
People with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) hamartomatous tumor syndromes (PHTS) have a mutation in one of their genes called PTEN that can lead to benign tumors called hamartomas throughout the body. This puts them at increased risk for breast, thyroid and endometrial cancer.
Read more
People with a PTEN mutation have increased activity of proteins such as protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which may be responsible for tumor growth and their increased risk of these cancers.
Experiments show that a drug called sirolimus, which is used to prevent the immune system from rejecting transplanted organs, can inhibit cancer cell growth by blocking the mTOR protein.
Objectives:
To test the ability of sirolimus to decrease the activity of proteins that are regulated by mTOR in both benign and cancerous tumor tissue.
Eligibility:
People 18 years of age and older with Cowden syndrome or other PHTS.
Design:
Sirolimus treatment. Patients take sirolimus once a day in 28-day treatment cycles. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
Evaluations. Patients come to the clinic for a history and physical examination on day 1 of every treatment cycle, then every month for the first two months off therapy, and then at 6 and 12 months. In addition, they have the following procedures:
- Positron emission tomography (PET) scan and neuropsychological testing before starting treatment.
- Clinical photography (photographic documentation of skin lesions) before starting treatment. Patients who do not have cancer have repeat photography at 2 and 8 weeks and then, if the lesions shrink or go away while on therapy, again every month for the first 2 months off sirolimus, then at 6 months and 1 year. Patients who have cancer and continue treatment beyond 8 weeks have repeat photography every 8 weeks while on the study.
- Digital dermoscopy (skin lesion examination using a high resolution camera). This is done at the same intervals as clinical photography.
- Multiple biopsies of the skin and lower intestine, and possibly the tumor in patients with cancer, before starting treatment, at 2 weeks of treatment and at 8 weeks of treatment.
- Blood and urine tests every week while on treatment for the first two cycles, then every 4 weeks for patients who continue treatment beyond two cycles.
- Imaging studies, such as computerized tomography (CT), ultrasound or magnetic resonance imaging (MRI) in patients with cancer before starting treatment and again every two cycles to monitor the tumor size and location.
Read the detailed description
Background:
- PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor gene whose function is frequently lost through genetic and epigenetic mechanisms in cancer. Loss of PTEN increases activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway, which increases cellular proliferation and survival.
- Germline mutations in PTEN are associated with a number of hamartomatous syndromes, of which Cowden Syndrome (CS) is the prototype. The set of syndromes that are defined by germline PTEN mutations has been labeled PTEN Hamartomatous Tumor Syndromes or PHTS.
- Patients with PHTS suffer increased morbidity and mortality. Benign tumors such as hamartomas occur in virtually every organ, most commonly in the skin and the gastrointestinal tract, which prompts frequent monitoring and resection and causes psychological and physical stressors on patients with this condition.
- Cowden syndrome (CS) patients develop thyroid, breast, and endometrial cancers at an earlier age than the general population, and have an overall increased incidence of these cancers compared to the general population. These patients have increased morbidity from heightened surveillance and diagnostic procedures.
- No medical therapies exist for PHTS patients.
- Because tumors from PHTS patients show increased activation of the PI3K/Akt/mTOR pathway, inhibitors of this pathway might have activity in patients with PHTS.
- Sirolimus (rapamycin) is a specific inhibitor of mTOR that is Food and Drug Administration (FDA)-approved and is preferentially effective in cells with mutant PTEN.
- We hypothesize that sirolimus will have activity in patients with PHTS, as measured by biochemical techniques that will assess mTOR inhibition and clinical tests that will assess the growth and metabolism of benign and malignant tumors.
Objectives:
- The primary endpoint will be inhibition of the mTOR pathway in tissues obtained before and after therapy, as assessed using immunohistochemistry in benign as well as malignant tumors.
- Secondary endpoints will include inhibition of the mTOR pathway in peripheral blood mononuclear cells (PBMCs) as assessed by immunoblotting, changes and duration of change in benign or malignant tumor size as assessed by computed tomography (CT), serial digital photography, digital dermoscopy, changes in tumor metabolism as assessed by positron emission tomography (PET), changes in lymphocyte counts, as well as changes in neuropsychological testing.
Eligibility:
-Adult subjects with documented germline PTEN mutations who meet diagnostic criteria for Cowden Syndrome by international criteria.
Design:
- Subjects will undergo biopsy, imaging, photography, dermoscopy, and neuropsychological testing prior to and after a course of therapy with sirolimus to assess the efficacy of treatment.
- This pilot protocol will test sirolimus at an FDA-approved dose (6 mg by mouth (PO) loading dose/ 2mg PO daily) in a group of twenty patients.
- Treatment will last for 56 days (plus 2 - 3 days to allow flexibility for scheduling of follow-up procedures) for PHTS subjects with benign hamartomatous tumors.
- For PHTS subjects with established malignancy, measurement of disease will be performed every other cycle and treatment will continue until disease progression or unacceptable toxicity.
- Conditions
- Cowden's Disease, Hamartoma Syndrome, Multiple
- Being tested
- fludeoxyglucose F 18, sirolimus, Clinical Videography
- Keywords
- Sirolimus, Cowden Syndrome, PTEN Mutation, Hamartoma Syndrome
- Medical subject headings
- Hamartoma Syndrome, Multiple
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fludeoxyglucose F 18Radiation
Also called FDG-18
Fludeoxyglucose is the radioactive material/compound used as an injection to have a PET scan performed.
sirolimusDrug
Also called Rapamune
sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects
Clinical VideographyOther
This examination involves testing of cerebellar function that controls movement, balance, and coordination.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus Patients | Experimental | sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects. Receives: Radiation: fludeoxyglucose F 18; Drug: sirolimus; Other: Clinical Videography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Changes in Benign and Malignant Tumor Tissues as Assessed by Immunohistochemistry.
A biochemical change is defined as a decrease in certain protein levels (e.g. P-AKT (phosphorylated AKT), total S6, P-S6, and P-4E-BP1) important in cell growth. These are measured by collecting tissue samples which stained and protein levels are measured under the microscope. Scoring will be based on distribution and intensity of staining. Distribution will be scored as 0 (0%), 1 (1% to 50%), and 2 (51% to 100%) to indicate the percentage of positive cells of interest in a single core. The intensity of the signal will be scored as 1 (weak), 2 (moderate), and 3 (strong). The distribution score and intensity score will be summed into a total score (TS).
Measured: Baseline, day 14, and day 56
Number of Participants With Adverse Events
Here is the number of participants with adverse events
Measured: 47 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2009 (estimated)
- Study startJul 2008
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cowden's DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Arun Rajan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00971789
- Sponsor's protocol ID
- 080151
- Other IDs
- 08-C-0151
- Status last verified
- Jul 2013
- First submitted
- 3 Sep 2009
- Last updated
- 30 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943-7. doi: 10.1126/science.275.5308.1943.
PubMed 9072974Zhou XP, Loukola A, Salovaara R, Nystrom-Lahti M, Peltomaki P, de la Chapelle A, Aaltonen LA, Eng C. PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. Am J Pathol. 2002 Aug;161(2):439-47. doi: 10.1016/S0002-9440(10)64200-9.
PubMed 12163369Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet. 2001 Jul 21;358(9277):210-1. doi: 10.1016/s0140-6736(01)05412-5.
PubMed 11476841Komiya T, Blumenthal GM, DeChowdhury R, Fioravanti S, Ballas MS, Morris J, Hornyak TJ, Wank S, Hewitt SM, Morrow B, Memmott RM, Rajan A, Dennis PA. A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN. Oncologist. 2019 Dec;24(12):1510-e1265. doi: 10.1634/theoncologist.2019-0514. Epub 2019 Jul 26.
PubMed 31350329Kalin A, Merideth MA, Regier DS, Blumenthal GM, Dennis PA, Stratton P. Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer. Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):461-464.
PubMed 23344409
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Sirolimus (Rapamycin, Rapamune[Registered Trademark]) in Subjects With Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN
- ClinicalTrials.gov ID
- NCT00971789
- Acronym / sponsor ID
- 080151
- Conditions
- Cowden's Disease, Hamartoma Syndrome, Multiple
- Keywords
- Sirolimus, Cowden Syndrome, PTEN Mutation, Hamartoma Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2008
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 4 Sep 2009 (estimated)
- Results
- Posted 19 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
People with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) hamartomatous tumor syndromes (PHTS) have a mutation in one of their genes called PTEN that can lead to benign tumors called hamartomas throughout the body. This puts them at increased risk for breast, thyroid and endometrial cancer.
People with a PTEN mutation have increased activity of proteins such as protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which may be responsible for tumor growth and their increased risk of these cancers.
Experiments show that a drug called sirolimus, which is used to prevent the immune system from rejecting transplanted organs, can inhibit cancer cell growth by blocking the mTOR protein.
Objectives:
To test the ability of sirolimus to decrease the activity of proteins that are regulated by mTOR in both benign and cancerous tumor tissue.
Eligibility:
People 18 years of age and older with Cowden syndrome or other PHTS.
Design:
Sirolimus treatment. Patients take sirolimus once a day in 28-day treatment cycles. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
Evaluations. Patients come to the clinic for a history and physical examination on day 1 of every treatment cycle, then every month for the first two months off therapy, and then at 6 and 12 months. In addition, they have the following procedures:
- Positron emission tomography (PET) scan and neuropsychological testing before starting treatment.
- Clinical photography (photographic documentation of skin lesions) before starting treatment. Patients who do not have cancer have repeat photography at 2 and 8 weeks and then, if the lesions shrink or go away while on therapy, again every month for the first 2 months off sirolimus, then at 6 months and 1 year. Patients who have cancer and continue treatment beyond 8 weeks have repeat photography every 8 weeks while on the study.
- Digital dermoscopy (skin lesion examination using a high resolution camera). This is done at the same intervals as clinical photography.
- Multiple biopsies of the skin and lower intestine, and possibly the tumor in patients with cancer, before starting treatment, at 2 weeks of treatment and at 8 weeks of treatment.
- Blood and urine tests every week while on treatment for the first two cycles, then every 4 weeks for patients who continue treatment beyond two cycles.
- Imaging studies, such as computerized tomography (CT), ultrasound or magnetic resonance imaging (MRI) in patients with cancer before starting treatment and again every two cycles to monitor the tumor size and location.
Detailed description
Background:
- PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor gene whose function is frequently lost through genetic and epigenetic mechanisms in cancer. Loss of PTEN increases activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway, which increases cellular proliferation and survival.
- Germline mutations in PTEN are associated with a number of hamartomatous syndromes, of which Cowden Syndrome (CS) is the prototype. The set of syndromes that are defined by germline PTEN mutations has been labeled PTEN Hamartomatous Tumor Syndromes or PHTS.
- Patients with PHTS suffer increased morbidity and mortality. Benign tumors such as hamartomas occur in virtually every organ, most commonly in the skin and the gastrointestinal tract, which prompts frequent monitoring and resection and causes psychological and physical stressors on patients with this condition.
- Cowden syndrome (CS) patients develop thyroid, breast, and endometrial cancers at an earlier age than the general population, and have an overall increased incidence of these cancers compared to the general population. These patients have increased morbidity from heightened surveillance and diagnostic procedures.
- No medical therapies exist for PHTS patients.
- Because tumors from PHTS patients show increased activation of the PI3K/Akt/mTOR pathway, inhibitors of this pathway might have activity in patients with PHTS.
- Sirolimus (rapamycin) is a specific inhibitor of mTOR that is Food and Drug Administration (FDA)-approved and is preferentially effective in cells with mutant PTEN.
- We hypothesize that sirolimus will have activity in patients with PHTS, as measured by biochemical techniques that will assess mTOR inhibition and clinical tests that will assess the growth and metabolism of benign and malignant tumors.
Objectives:
- The primary endpoint will be inhibition of the mTOR pathway in tissues obtained before and after therapy, as assessed using immunohistochemistry in benign as well as malignant tumors.
- Secondary endpoints will include inhibition of the mTOR pathway in peripheral blood mononuclear cells (PBMCs) as assessed by immunoblotting, changes and duration of change in benign or malignant tumor size as assessed by computed tomography (CT), serial digital photography, digital dermoscopy, changes in tumor metabolism as assessed by positron emission tomography (PET), changes in lymphocyte counts, as well as changes in neuropsychological testing.
Eligibility:
-Adult subjects with documented germline PTEN mutations who meet diagnostic criteria for Cowden Syndrome by international criteria.
Design:
- Subjects will undergo biopsy, imaging, photography, dermoscopy, and neuropsychological testing prior to and after a course of therapy with sirolimus to assess the efficacy of treatment.
- This pilot protocol will test sirolimus at an FDA-approved dose (6 mg by mouth (PO) loading dose/ 2mg PO daily) in a group of twenty patients.
- Treatment will last for 56 days (plus 2 - 3 days to allow flexibility for scheduling of follow-up procedures) for PHTS subjects with benign hamartomatous tumors.
- For PHTS subjects with established malignancy, measurement of disease will be performed every other cycle and treatment will continue until disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus Patients | Experimental | Radiation: fludeoxyglucose F 18, Drug: sirolimus, Other: Clinical Videographysirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- Pregnant or lactating women, due to potentially harmful effects of sirolimus on the embryo or fetus or nursing child.
- Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.
- Patients taking immuno-suppressive agents other than prescribed corticosteroids, which must not exceed the equivalent of 20 mg/d of prednisone.
- Patients that are on the following cytochrome P450 3A4 (CYP3A4) inhibitors and cannot replace these medications with other equivalent medications for the period of the study: protease inhibitors, cyclosporine, fluconazole, itraconazole, ketoconazole, metoclopramide, felodipine, nifedipine, carbamazepine, Phenobarbital, grapefruit juice, and St. John's Wort.
- Patients who have received live vaccines in the past 30 days.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fludeoxyglucose F 18Also: FDG-18Fludeoxyglucose is the radioactive material/compound used as an injection to have a PET scan performed. | Radiation | Sirolimus Patients |
| sirolimusAlso: Rapamunesirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects | Drug | Sirolimus Patients |
| Clinical VideographyThis examination involves testing of cerebellar function that controls movement, balance, and coordination. | Other | Sirolimus Patients |
Primary outcome
Biochemical Changes in Benign and Malignant Tumor Tissues as Assessed by Immunohistochemistry.
Time frame: Baseline, day 14, and day 56
A biochemical change is defined as a decrease in certain protein levels (e.g. P-AKT (phosphorylated AKT), total S6, P-S6, and P-4E-BP1) important in cell growth. These are measured by collecting tissue samples which stained and protein levels are measured under the microscope. Scoring will be based on distribution and intensity of staining. Distribution will be scored as 0 (0%), 1 (1% to 50%), and 2 (51% to 100%) to indicate the percentage of positive cells of interest in a single core. The intensity of the signal will be scored as 1 (weak), 2 (moderate), and 3 (strong). The distribution score and intensity score will be summed into a total score (TS).
Number of Participants With Adverse Events
Time frame: 47 months
Here is the number of participants with adverse events
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9072974Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943-7. doi: 10.1126/science.275.5308.1943.
- Background: PubMed 12163369Zhou XP, Loukola A, Salovaara R, Nystrom-Lahti M, Peltomaki P, de la Chapelle A, Aaltonen LA, Eng C. PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. Am J Pathol. 2002 Aug;161(2):439-47. doi: 10.1016/S0002-9440(10)64200-9.
- Background: PubMed 11476841Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet. 2001 Jul 21;358(9277):210-1. doi: 10.1016/s0140-6736(01)05412-5.
- Derived from this study: PubMed 31350329Komiya T, Blumenthal GM, DeChowdhury R, Fioravanti S, Ballas MS, Morris J, Hornyak TJ, Wank S, Hewitt SM, Morrow B, Memmott RM, Rajan A, Dennis PA. A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN. Oncologist. 2019 Dec;24(12):1510-e1265. doi: 10.1634/theoncologist.2019-0514. Epub 2019 Jul 26.
- Derived from this study: PubMed 23344409Kalin A, Merideth MA, Regier DS, Blumenthal GM, Dennis PA, Stratton P. Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer. Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):461-464.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arun Rajan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing fludeoxyglucose F 18, sirolimus and Clinical Videography in people with Cowden's Disease and Hamartoma Syndrome, Multiple, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biochemical Changes in Benign and Malignant Tumor Tissues as Assessed by Immunohistochemistry. (time frame: Baseline, day 14, and day 56). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00971789, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2015.