PIK3CA-Related Overgrowth Spectrum (PROS)Phase 2NCT02428296
Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation
A Phase 2 study testing Sirolimus in people with PIK3CA-Related Overgrowth Spectrum (PROS) and Growth Disorder, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Background: PIK3CA-related overgrowth spectrum (PROS) is caused by changes in the PIK3CA gene. This gene makes a protein that communicates with other proteins in the body to cause cells to grow. Alterations in PIK3CA change the chemical signals in the body and cause overgrowth in fatty, vascular and other tissues. Read more about this study
- Who is it for?
- Ages 3 to 65 years
- Conditions the study is for
- PIK3CA-Related Overgrowth Spectrum (PROS), Growth Disorder, Genetics
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2015to 14 Feb 2018
- 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 3 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: greater than or equal to 3 years to less than or equal to 65 years
- Male or Female
- Confirmed PIK3CA somatic mutation
- Measurably progressive overgrowth, in current progression or with clinical history of overgrowth progression
- Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) greater than or equal to 1500/microliter, except for those participants with an absolute neutrophil count (ANC) of 1000-1500, caused by a benign condition associated with moderately decreased neutrophils known as Benign Ethnic Neutropenia (BEN), d those who have an ANC of 1000-1500 caused by a confirmed infection, which resolves with treatment of infection to greater than or equal to 1500.
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- Platelet count less than or equal to 100,000/microliter
- Hemoglobin less than or equal to 10.0 gm/dL
- Adequate Renal Function Defined as:
- A serum creatinine based on age as follows:
- Age (years) [Maximum Serum Creatinine (mg/dl)]
- Less than or equal to 5 [0.8 mg/dl]
- 5 less than age less than or equal to10 [1.0 mg/dl]
- 10 less than age less than or equal to 15 [1.2 mg/dl]
- Less than 15 [1.5 mg/dl]
- OR a creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2
- Adequate Liver Function Defined As:
- Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age, and
- SGPT (ALT) less than or equal to 5 x upper limit of normal (ULN) for age, and
- Serum albumin greater than or equal to 2 g/dL.
- Fasting LDL Cholesterol:
- Patients must have a fasting LDL cholesterol of less than or equal to 160 mg/d
- All women of childbearing potential and all sexually active male patients must agree to use effective contraception
- Adolescent (15-17 year old) participants who are fluent in English and can thereby complete the pediatric self-report questionnaires and communicate well with the study team but whose parent(s) and/or legal guardian are primarily Spanish-speaking.
Who cannot join
- The participant may not enter the study if ANY of the following apply:
- Age less than 3 years or greater than 65 years
- Pregnant or breastfeeding
- Women and men of reproductive age without an effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
- Hypersensitivity to sirolimus or any of the excipients
- Any current medical disorder or medication likely to impair ability to follow the study protocol safely and effectively
Show all 17Show fewer
- Incapacity to give informed consent
- Sirolimus treatment in the prior 4 weeks
- If less than 3 months post-surgery
- Prior malignancy or ongoing investigations for malignancy
- Active skin infections requiring antibiotics or anti-viral medication
- HCV/HBV/HIV seropositivity
- Previous/ active MTB infection
- Pneumonitis
- Research radiation exposure within previous 12 months
- Adult participants or participants under the age of 15 years with insufficient English language proficiency to complete informed consent and quality of life measures
- We propose to restrict participation in this study to those with sufficient English language skills to complete the quality of life measures we will employ among all three study sites, as many of the specific quality of life measures we are employing at the NIH only are not available in other languages.
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: Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation
Background:
- PIK3CA-related overgrowth spectrum (PROS) is caused by changes in the PIK3CA gene. This gene makes a protein that communicates with other proteins in the body to cause cells to grow. Alterations in PIK3CA change the chemical signals in the body and cause overgrowth in fatty, vascular and other tissues. Sirolimus is a drug that reduces the signals sent by one of the proteins in this chemical signaling pathway. Researchers want to learn whether the drug sirolimus can reduce or stabilize some of the overgrowth that patients with PROS experience.
Read more
Objectives:
- To measure how the overgrowth of patients with PROS changes over time and whether taking a drug called sirolimus can reduce or stabilize a person s overgrowth.
Eligibility:
- People ages 3 to 65 years old with a confirmed mutation or alteration of the PIK3CA gene in the person s affected tissues (a somatic mutation).
Design:
- Participants will be screened with medical history and genetic counseling.
- First 6 months: Participants will have their overgrowth monitored.
- Next 6 months: Participants will take sirolimus once or twice a day.
- Participants will have to visit the clinic several times, and stay in the area for 4 to 5 days each time.
- Participants will have a one month-long visit to the clinic.
- During clinic visits, participants will have:
- Blood and urine tests.
- Photographs of their physical features.
- Scans, including an MRI and DEXA, and possibly x-rays and CT scans.
- For the MRI and CT scans, participants will lie in a machine that takes pictures of their body.
- The DEXA involves a small amount of radiation.
- They may have:
- Non-invasive heart function tests.
- Lung function tests.
- Participants will have several blood and urine tests between visits.
- Participants will complete surveys and keep a diary of their treatment and side effects.
- Participants may visit other health specialists or undergo other tests based on side effects.
- One month after stopping the study drug, participants will have 1 clinic visit.
Read the detailed description
The primary study objective is to determine the likely size of sirolimus treatment effect. The patient population will include male and female subjects, aged greater than or equal to 3 years and less than or equal to 65 years of age with segmental overgrowth identified to have clinical and molecular findings of somatic PIK3CA gene mutation. The planned study size will be ten patients seen at the NIHCC. An additional 20 patients will be contributed by two other centers, who will be responsible for the conduct of the proposed research at their site, but the study procedures and dosing schedule will be identical to enable pooling of results for statistical analyses. The study design will be a nonrandomized, open label, phase II pilot study of sirolimus treatment. As patients have highly variable clinical presentations, and there are no established evidence-based methodologies for measuring serial changes in growth, the aim of this pilot study is to establish the optimal methodology for evaluating changes in growth to inform the design of a future randomized controlled trial, in addition to determining treatment effect size, and evaluating safety and toxicity of low dose sirolimus. Overall desired outcome will be reduced size of affected body part, and measures will include: reduction in affected tissue (fibroadipose or bone) size by clinical exam measurement and by radiological studies (MRI area measurements and/or DXA study measurements of fat).
- Being tested
- Sirolimus
- Keywords
- Clinical Trial, Congenital Malformations, Overgrowth, Pilot Drug Treatment Trial
- Medical subject headings
- Growth Disorders, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Low dose sirolimus will be given in daily dosing to achieve trough levels of 2-6 ng/ ml.
| Study group | Role | What they receive |
|---|---|---|
| Patients with PIK3CA gene mutation treated with Sirolimus | Experimental | This is a single-arm, non-randomized, open-label study for the treatment of segmental overgrowth disorders (somatic PIK3CA gene mutation) with Sirolimus in thirty-nine patients. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Unaffected and Affected Fibrofatty Tissue Measured by DXA
The primary outcome measures will use quantitative DXA scan of the affected and unaffected body part (s) to demonstrate negative change in fibrofatty, muscular, and/or bony overgrowth.
Absolute volumes of affected and unaffected tissue at week 0 (designated X), week 26 (designated Y), and week 52 (designated Z), were compared by taking the difference between the mean value obtained during the run-in period and the mean value obtained during the treatment period. Tissue volume changes (week 0-26 and week 26-52) were designated "DELTA," and the percent change "% Change." Percent change for the untreated period was [100(Y-X/X)], and for the treated period [100(Z-Y/Y)].
Measured: Run-in (0-26 weeks), treatment (26-52 weeks)
Percent Change in Unaffected and Affected Fibrofatty Tissue Measured by MRI Scan
The outcome was measured as a percent change in tissue volume between the treatment period and run-in period.
For volume calculation, IDEAL fat (Dixon sequence) images were visualized using volumetric software (SliceOmatic, TomoVision, Magog, Canada). Morphology segmentation was performed through computation of watershed gradients. Tissues (fat, muscle, bone, and blood vessel) were manually defined and software was used to generate a surrogate of tissue volume using five slices, with manual adjustments where required.
Absolute volumes of affected and unaffected tissue at week 0 (designated X), week 26 (designated Y), and week 52 (designated Z), were compared. Tissue volume changes (week 0-26 and week 26-52) were designated "DELTA," and the percent change "% Change." Percent change for the untreated period was [100(Y-X/X)], and for the treated period [100(Z-Y/Y)].
Measured: Run-in (0-26 weeks), treatment (26-52 weeks)
Secondary outcomes (3)
Mean Sirolimus Doses to Achieve the Target Plasma Concentration
To establish optimal sirolimus dosing algorithms for a future RCT.
Measured: Between 6 months and 12 months
Additional Measure of Efficacy: Quality of Life Assessment
The World Health Organization Quality of Life-BREF (WHOQOL-BREF) assessment measures four domains related to quality of life (physical health, psychological, social relationships, and environment) and produces both individual domain scores (0-100) a total score on a 0-100 scale (high scores indicate a better quality of life). This measure was used to assess quality of life of parents on behalf of their children, and adult subjects.
The Pediatric Quality of Life (PedsQL) assessment is scored on a 0-100 scale (high scores indicate a better health related quality of life). This measure was used to assess quality of life of children.
The outcomes are reported as a change in quality of life based on the change in scores from these assessments between baseline (time 0 months) and end of treatment (time 12 months).
Measured: baseline (0 months) and end of treatment (12 months)
Number of Hospitalizations and Surgical Interventions
Tracked number of hospitalizations and surgical interventions occurring over the course of the run-in and treatment period.
Measured: Run-in (0-26 weeks) and treatment (27-52 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2015 (estimated)
- Study start23 Apr 2015
- Primary completion14 Feb 2018
- Study completion14 Feb 2018
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 (4)Papers the sponsor has linked to this study.
- Other trials for PIK3CA-Related Overgrowth Spectrum (PROS)Studies of the same condition, open and under way.
- 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
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kim M Keppler-Noreuil, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02428296
- Sponsor's protocol ID
- 150120
- Other IDs
- 15-HG-0120
- Status last verified
- 14 Feb 2018
- First submitted
- 23 Apr 2015
- Last updated
- 5 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Lindhurst MJ, Parker VE, Payne F, Sapp JC, Rudge S, Harris J, Witkowski AM, Zhang Q, Groeneveld MP, Scott CE, Daly A, Huson SM, Tosi LL, Cunningham ML, Darling TN, Geer J, Gucev Z, Sutton VR, Tziotzios C, Dixon AK, Helliwell T, O'Rahilly S, Savage DB, Wakelam MJ, Barroso I, Biesecker LG, Semple RK. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet. 2012 Jun 24;44(8):928-33. doi: 10.1038/ng.2332.
PubMed 22729222Keppler-Noreuil KM, Rios JJ, Parker VE, Semple RK, Lindhurst MJ, Sapp JC, Alomari A, Ezaki M, Dobyns W, Biesecker LG. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015 Feb;167A(2):287-95. doi: 10.1002/ajmg.a.36836. Epub 2014 Dec 31.
PubMed 25557259Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, Parker VE, Blumhorst C, Darling T, Tosi LL, Huson SM, Whitehouse RW, Jakkula E, Grant I, Balasubramanian M, Chandler KE, Fraser JL, Gucev Z, Crow YJ, Brennan LM, Clark R, Sellars EA, Pena LD, Krishnamurty V, Shuen A, Braverman N, Cunningham ML, Sutton VR, Tasic V, Graham JM Jr, Geer J Jr, Henderson A, Semple RK, Biesecker LG. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014 Jul;164A(7):1713-33. doi: 10.1002/ajmg.a.36552. Epub 2014 Apr 29.
PubMed 24782230Parker VER, Keppler-Noreuil KM, Faivre L, Luu M, Oden NL, De Silva L, Sapp JC, Andrews K, Bardou M, Chen KY, Darling TN, Gautier E, Goldspiel BR, Hadj-Rabia S, Harris J, Kounidas G, Kumar P, Lindhurst MJ, Loffroy R, Martin L, Phan A, Rother KI, Widemann BC, Wolters PL, Coubes C, Pinson L, Willems M, Vincent-Delorme C; PROMISE Working Group; Vabres P, Semple RK, Biesecker LG. Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum. Genet Med. 2019 May;21(5):1189-1198. doi: 10.1038/s41436-018-0297-9. Epub 2018 Oct 1.
PubMed 30270358
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation
- ClinicalTrials.gov ID
- NCT02428296
- Acronym / sponsor ID
- 150120
- Keywords
- Clinical Trial, Congenital Malformations, Overgrowth, Pilot Drug Treatment Trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 23 Apr 2015
- Primary completion
- 14 Feb 2018 (actual)
- Study completion
- 14 Feb 2018 (actual)
- First posted
- 28 Apr 2015 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- PIK3CA-related overgrowth spectrum (PROS) is caused by changes in the PIK3CA gene. This gene makes a protein that communicates with other proteins in the body to cause cells to grow. Alterations in PIK3CA change the chemical signals in the body and cause overgrowth in fatty, vascular and other tissues. Sirolimus is a drug that reduces the signals sent by one of the proteins in this chemical signaling pathway. Researchers want to learn whether the drug sirolimus can reduce or stabilize some of the overgrowth that patients with PROS experience.
Objectives:
- To measure how the overgrowth of patients with PROS changes over time and whether taking a drug called sirolimus can reduce or stabilize a person s overgrowth.
Eligibility:
- People ages 3 to 65 years old with a confirmed mutation or alteration of the PIK3CA gene in the person s affected tissues (a somatic mutation).
Design:
- Participants will be screened with medical history and genetic counseling.
- First 6 months: Participants will have their overgrowth monitored.
- Next 6 months: Participants will take sirolimus once or twice a day.
- Participants will have to visit the clinic several times, and stay in the area for 4 to 5 days each time.
- Participants will have a one month-long visit to the clinic.
- During clinic visits, participants will have:
- Blood and urine tests.
- Photographs of their physical features.
- Scans, including an MRI and DEXA, and possibly x-rays and CT scans.
- For the MRI and CT scans, participants will lie in a machine that takes pictures of their body.
- The DEXA involves a small amount of radiation.
- They may have:
- Non-invasive heart function tests.
- Lung function tests.
- Participants will have several blood and urine tests between visits.
- Participants will complete surveys and keep a diary of their treatment and side effects.
- Participants may visit other health specialists or undergo other tests based on side effects.
- One month after stopping the study drug, participants will have 1 clinic visit.
Detailed description
The primary study objective is to determine the likely size of sirolimus treatment effect. The patient population will include male and female subjects, aged greater than or equal to 3 years and less than or equal to 65 years of age with segmental overgrowth identified to have clinical and molecular findings of somatic PIK3CA gene mutation. The planned study size will be ten patients seen at the NIHCC. An additional 20 patients will be contributed by two other centers, who will be responsible for the conduct of the proposed research at their site, but the study procedures and dosing schedule will be identical to enable pooling of results for statistical analyses. The study design will be a nonrandomized, open label, phase II pilot study of sirolimus treatment. As patients have highly variable clinical presentations, and there are no established evidence-based methodologies for measuring serial changes in growth, the aim of this pilot study is to establish the optimal methodology for evaluating changes in growth to inform the design of a future randomized controlled trial, in addition to determining treatment effect size, and evaluating safety and toxicity of low dose sirolimus. Overall desired outcome will be reduced size of affected body part, and measures will include: reduction in affected tissue (fibroadipose or bone) size by clinical exam measurement and by radiological studies (MRI area measurements and/or DXA study measurements of fat).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with PIK3CA gene mutation treated with Sirolimus | Experimental | Drug: SirolimusThis is a single-arm, non-randomized, open-label study for the treatment of segmental overgrowth disorders (somatic PIK3CA gene mutation) with Sirolimus in thirty-nine patients. |
Who may qualify
- Ages
- 3 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Age: greater than or equal to 3 years to less than or equal to 65 years
- Male or Female
- Confirmed PIK3CA somatic mutation
- Measurably progressive overgrowth, in current progression or with clinical history of overgrowth progression
- Adequate Bone Marrow Function Defined as:
Key exclusion criteria (17 listed)
- Age less than 3 years or greater than 65 years
- Pregnant or breastfeeding
- Women and men of reproductive age without an effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
- Hypersensitivity to sirolimus or any of the excipients
- Any current medical disorder or medication likely to impair ability to follow the study protocol safely and effectively
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 |
|---|---|---|
| SirolimusLow dose sirolimus will be given in daily dosing to achieve trough levels of 2-6 ng/ ml. | Drug | Patients with PIK3CA gene mutation treated with Sirolimus |
Primary outcome
Percent Change in Unaffected and Affected Fibrofatty Tissue Measured by DXA
Time frame: Run-in (0-26 weeks), treatment (26-52 weeks)
The primary outcome measures will use quantitative DXA scan of the affected and unaffected body part (s) to demonstrate negative change in fibrofatty, muscular, and/or bony overgrowth. Absolute volumes of affected and unaffected tissue at week 0 (designated X), week 26 (designated Y), and week 52 (designated Z), were compared by taking the difference between the mean value obtained during the run-in period and the mean value obtained during the treatment period. Tissue volume changes (week 0-26 and week 26-52) were designated "DELTA," and the percent change "% Change." Percent change for the untreated period was [100(Y-X/X)], and for the treated period [100(Z-Y/Y)].
Percent Change in Unaffected and Affected Fibrofatty Tissue Measured by MRI Scan
Time frame: Run-in (0-26 weeks), treatment (26-52 weeks)
The outcome was measured as a percent change in tissue volume between the treatment period and run-in period. For volume calculation, IDEAL fat (Dixon sequence) images were visualized using volumetric software (SliceOmatic, TomoVision, Magog, Canada). Morphology segmentation was performed through computation of watershed gradients. Tissues (fat, muscle, bone, and blood vessel) were manually defined and software was used to generate a surrogate of tissue volume using five slices, with manual adjustments where required. Absolute volumes of affected and unaffected tissue at week 0 (designated X), week 26 (designated Y), and week 52 (designated Z), were compared. Tissue volume changes (week 0-26 and week 26-52) were designated "DELTA," and the percent change "% Change." Percent change for the untreated period was [100(Y-X/X)], and for the treated period [100(Z-Y/Y)].
3 secondary outcomes
Mean Sirolimus Doses to Achieve the Target Plasma Concentration
Time frame: Between 6 months and 12 months
Additional Measure of Efficacy: Quality of Life Assessment
Time frame: baseline (0 months) and end of treatment (12 months)
Number of Hospitalizations and Surgical Interventions
Time frame: Run-in (0-26 weeks) and treatment (27-52 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22729222Lindhurst MJ, Parker VE, Payne F, Sapp JC, Rudge S, Harris J, Witkowski AM, Zhang Q, Groeneveld MP, Scott CE, Daly A, Huson SM, Tosi LL, Cunningham ML, Darling TN, Geer J, Gucev Z, Sutton VR, Tziotzios C, Dixon AK, Helliwell T, O'Rahilly S, Savage DB, Wakelam MJ, Barroso I, Biesecker LG, Semple RK. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet. 2012 Jun 24;44(8):928-33. doi: 10.1038/ng.2332.
- Background: PubMed 25557259Keppler-Noreuil KM, Rios JJ, Parker VE, Semple RK, Lindhurst MJ, Sapp JC, Alomari A, Ezaki M, Dobyns W, Biesecker LG. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015 Feb;167A(2):287-95. doi: 10.1002/ajmg.a.36836. Epub 2014 Dec 31.
- Background: PubMed 24782230Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, Parker VE, Blumhorst C, Darling T, Tosi LL, Huson SM, Whitehouse RW, Jakkula E, Grant I, Balasubramanian M, Chandler KE, Fraser JL, Gucev Z, Crow YJ, Brennan LM, Clark R, Sellars EA, Pena LD, Krishnamurty V, Shuen A, Braverman N, Cunningham ML, Sutton VR, Tasic V, Graham JM Jr, Geer J Jr, Henderson A, Semple RK, Biesecker LG. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014 Jul;164A(7):1713-33. doi: 10.1002/ajmg.a.36552. Epub 2014 Apr 29.
- Results publication: PubMed 30270358Parker VER, Keppler-Noreuil KM, Faivre L, Luu M, Oden NL, De Silva L, Sapp JC, Andrews K, Bardou M, Chen KY, Darling TN, Gautier E, Goldspiel BR, Hadj-Rabia S, Harris J, Kounidas G, Kumar P, Lindhurst MJ, Loffroy R, Martin L, Phan A, Rother KI, Widemann BC, Wolters PL, Coubes C, Pinson L, Willems M, Vincent-Delorme C; PROMISE Working Group; Vabres P, Semple RK, Biesecker LG. Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum. Genet Med. 2019 May;21(5):1189-1198. doi: 10.1038/s41436-018-0297-9. Epub 2018 Oct 1.
- 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.
Kim M Keppler-Noreuil, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
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 Sirolimus in people with PIK3CA-Related Overgrowth Spectrum (PROS) and Growth Disorder, run by National Human Genome Research Institute (NHGRI) 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 24 inclusion and 17 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 5 Feb 2020. 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 27 Jan 2020). 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?
Percent Change in Unaffected and Affected Fibrofatty Tissue Measured by DXA (time frame: Run-in (0-26 weeks), treatment (26-52 weeks)). 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 NCT02428296, which also lists 4 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 5 Feb 2020.