Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)

ClinicalTrials.gov Identifier:

NCT00971789

First received: September 3, 2009

Last updated: September 29, 2015

Last verified: July 2013

History of Changes

Results First Received: May 3, 2013

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Cowden's Disease Hamartoma Syndrome, Multiple
Interventions:	Radiation: fludeoxyglucose F 18 Drug: sirolimus Other: Clinical Videography

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Sirolimus Patients	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.

Participant Flow: Overall Study

	Sirolimus Patients
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Sirolimus Patients	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.

Baseline Measures

	Sirolimus Patients
Overall Participants Analyzed [Units: Participants]	18

Age [Units: Participants]
<=18 years	0
Between 18 and 65 years	15
>=65 years	3

Age [Units: Years] Mean (Standard Deviation)	43.54 (15.54)

Gender [Units: Participants]
Female	9
Male	9

Ethnicity (NIH/OMB) [Units: Participants]
Hispanic or Latino	0
Not Hispanic or Latino	18
Unknown or Not Reported	0

Race (NIH/OMB) [Units: Participants]
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	17
More than one race	0
Unknown or Not Reported	0

Region of Enrollment [Units: Participants]
United States	18

Outcome Measures

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1. Primary:

Biochemical Changes in Benign and Malignant Tumor Tissues as Assessed by Immunohistochemistry. [ Time Frame: Baseline, day 14, and day 56 ]

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2. Primary:

Number of Participants With Adverse Events [ Time Frame: 47 months ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Sirolimus Patients	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.

Other Adverse Events

	Sirolimus Patients
Total, Other (not including serious) Adverse Events
# participants affected / at risk	17/18 (94.44%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (anemia) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
CD4 count ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Edema: limb ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Leukocytes (total WBC) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Lymphopenia ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	5
Neutrophils/granulocytes (ANC/AGC) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
PTT (Partial Thromboplastin Time) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	2
Platelets ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Gastrointestinal disorders
Constipation ^† 1
# participants affected / at risk	4/18 (22.22%)
# events	4
Dental: teeth ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Diarrhea ^† 1
# participants affected / at risk	6/18 (33.33%)
# events	9
Distension/bloating, abdominal ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Flatulence ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Gastritis (including bile reflux gastritis) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Gastrointestinal - Other (bloating) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Hemorrhage, GI::Colon ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Mucositis/stomatitis (clinical exam)::Oral cavity ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	3
Nausea ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Pain::Abdomen NOS ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	3
General disorders
Fatigue (asthenia, lethargy, malaise) ^† 1
# participants affected / at risk	7/18 (38.89%)
# events	7
Insomnia ^† 1
# participants affected / at risk	4/18 (22.22%)
# events	5
Pain - Other (R/costal vert. angle; R/flank; shoulder) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	3
Rigors/chills ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Infection with unknown ANC::Sinus ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase) ^† 1
# participants affected / at risk	7/18 (38.89%)
# events	12
AST, SGOT(serum glutamic oxaloacetic transaminase) ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	5
Albumin, serum-low (hypoalbuminemia) ^† 1
# participants affected / at risk	7/18 (38.89%)
# events	9
Alkaline phosphatase ^† 1
# participants affected / at risk	5/18 (27.78%)
# events	5
Bilirubin (hyperbilirubinemia) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	3
Calcium, serum-high (hypercalcemia) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Cholesterol, serum-high (hypercholesteremia) ^† 1
# participants affected / at risk	5/18 (27.78%)
# events	5
Glucose, serum-high (hyperglycemia) ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	4
Glucose, serum-low (hypoglycemia) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Hemoglobin ^† 1
# participants affected / at risk	7/18 (38.89%)
# events	9
Lipase ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Magnesium, serum-high (hypermagnesemia) ^† 1
# participants affected / at risk	4/18 (22.22%)
# events	4
Magnesium, serum-low (hypomagnesemia) ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	4
Phosphate, serum-low (hypophosphatemia) ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	6
Proteinuria ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Sodium, serum-high (hypernatremia) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Sodium, serum-low (hyponatremia) ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Triglyceride, serum-high (hypertriglyceridemia) ^† 1
# participants affected / at risk	5/18 (27.78%)
# events	5
Uric acid, serum-high (hyperuricemia) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Musculoskeletal and connective tissue disorders
Pain::Extremity-limb ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Pain::Joint ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Pain::Muscle ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	3
Pain::Neck ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Nervous system disorders
Memory impairment ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Mood alteration::Depression ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Neuropathy: sensory ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Pain::Head/headache ^† 1
# participants affected / at risk	4/18 (22.22%)
# events	4
Renal and urinary disorders
Urine color change ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Reproductive system and breast disorders
Irregular menses (change from baseline) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Respiratory, thoracic and mediastinal disorders
Cough ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Pain::Throat/pharynx/larynx ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Skin and subcutaneous tissue disorders
Dry skin ^† 1
# participants affected / at risk	3/18 (16.67%)
# events	3
Rash/desquamation ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Rash: acne/acneiform ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1
Rash: hand-foot skin reaction ^† 1
# participants affected / at risk	2/18 (11.11%)
# events	2
Vascular disorders
Vascular - Other (venous insufficiency) ^† 1
# participants affected / at risk	1/18 (5.56%)
# events	1

†	Events were collected by systematic assessment
1	Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:

Name/Title: Dr. Arun Rajan
Organization: National Cancer Institute, National Institutes of Health
phone: 301-594-5322
e-mail: rajana@mail.nih.gov

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.

Zhou XP, Loukola A, Salovaara R, Nystrom-Lahti M, Peltomäki 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.

Zhou 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kalin 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):461-4. doi: http://10 1097/AOG.0b013e318270444f.

Responsible Party:	Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00971789 History of Changes
Obsolete Identifiers:	NCT00722449
Other Study ID Numbers:	080151 08-C-0151
Study First Received:	September 3, 2009
Results First Received:	May 3, 2013
Last Updated:	September 29, 2015

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