Pulmonary LymphangioleiomyomatosisPhase 2SLAM-2NCT02737202
Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis
A Phase 2 study testing saracatinib in people with Pulmonary Lymphangioleiomyomatosis, run by Baylor College of Medicine at 5 sites in United States.
Trial summary
This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Pulmonary Lymphangioleiomyomatosis
- What is being tested?
- saracatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2016to 30 Jul 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients. It should be noted that LAM occurs almost exclusively in women.
- 18 to 65 years of age.
- All patients must have a diagnosis of LAM as defined by compatible cystic changes on chest computed tomography (CT) and one of the following:
- Open lung, transbronchial or thoracic needle biopsy consistent with LAM
- Open or needle abdominal biopsy findings consistent with LAM
- Clinical findings of tuberous scleroma complex (TSC), renal angiomyolipoma, cystic abdominal lymphangiomas, or history of chylous effusion in the chest or abdomen
- Serum vascular endothelial growth factor D (VEGF-D) > 800 pg/ml
- Subjects must have had a recent reduction in forced expiratory volume at 1-second (FEV1) of > 50ml/year, as shown by at least two pulmonary function testing (PFT) measured at least 6 months apart in the last 24 months prior to enrolling study.
Who cannot join
- Current infection.
- Major surgery within the past 2 months
- Advanced hematologic, renal, hepatic, non-LAM lung disease or metabolic diseases; or BMI of >35
- The use of another investigational drug within 30 days
- The use of mTOR (mammalian target of rapamycin) inhibitors within 30 days
- Previous lung transplantation.
Show all 14Show fewer
- Inability to attend scheduled clinic visits
- Inability to give informed consent
- Inability to perform pulmonary function testing
- History of malignancy in the past two years, other than squamous or basal cell skin cancer or status post successful excision or treatment.
- Nursing mothers
- Current or planned pregnancy.
- Not using adequate contraception (in woman of childbearing potential).
- Significant clinical change in health in the past 30 days
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Laboratory of Translational Research NHLBI
Bethesda, Maryland, 20814
Loyola Medical Center
Chicago, Illinois, 90153
University of Cincinnati
Cincinnati, Ohio, 45267
Baylor College of Medicine - Ben Taub General Hospital
Houston, Texas, 77030
Stanford University
Stanford, California, 94305
About this study
This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.
Read the detailed description
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 tumor suppressor genes. TSC is characterized by tumors in a wide range of tissues, seizures, mental retardation, autism, and organ failure. Lymphangioleiomyomatosis (LAM), the major pulmonary manifestation in women with TSC, is a progressive lung disease characterized by infiltration of atypical smooth muscle like cells (TSC-/- LAM cells) and formation of parenchymal cysts. Sporadic LAM can develop in women who do not meet the criteria for the diagnosis of TSC, owing to somatic mutations in the TSC2 gene.
The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation is reminiscent of cells undergoing epithelial-mesenchymal transition (EMT). Src kinases are key regulators of cellular proliferation, motility, invasiveness and EMT. Recent results have shown that autophagy promotes degradation of active Src. Thereby, decreased autophagy due to mTOR activation known to occur in LAM cells, may play a significant role in accumulation of active Src in these cells. Src suppresses transcription of E-cadherin by upregulating its transcriptional repressors. The preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in cultured TSC2-/- cells. Further, in TSC2-/- cells, E-cadherin is considerably reduced and does not localize to the plasma membrane, as it does in wild-type cells.
The focus of this study is to examine if Src inhibition represents a potential therapeutic strategy in LAM. It is proposed that Src activation in TSC2-/- cells results in the reduction of E-cadherin, loss of cell-cell adhesion and elevation of oncogenic and metastatic potential of these cells. The increased Src activity in TSC2-/- cells is likely caused by inhibition of autophagy associated with hyper-activation of mTOR. Therefore, the use of Src inhibitors may lead to a reduction in tumor growth and prevent dissemination of TSC2-/- cells. In this study, the investigators will evaluate the safety and efficacy of Src inhibition in subjects with LAM.
A number of inhibitors of Src are now in clinical trials in patients with a range of different tumors. Dasatinib, an oral adenosine triphosphate (ATP)-competitive Src inhibitor, is now approved for clinical use in patients with chronic myeloid leukemia or acute lymphoblastic leukemia. However, dasatinib has wider 'off target' inhibitory activity than saracatinib including potent activity against Abl, ephrin receptor kinases, platelet-derived growth factor receptor and c-KIT (type of receptor tyrosine kinase and a type of tumor marker. Also called CD117 and stem cell factor receptor.) In contrast, saracatinib has a >10-fold preference for Src over Abl kinases and has very little activity against other tyrosine and serine/threonine kinases. Saracatinib has been already characterized in multiple clinical trials in terms of safety and pharmacokinetics.
The investigators have conducted a Phase1b study to test the safety of various doses of Saracatinib in LAM subjects. The purpose of the Phase1b trial was to determine the optimal dose in terms of safety and tolerability in LAM population. Three escalating doses of saracatinib; 50, 125 and 175 mg were studied. Saracatinib was given orally once a day. Overall, subjects tolerated Saracatinib well. The investigators chose the dose of 125 mg to conduct further testing of both safety and efficacy in this Phase 2a trial.
- Conditions
- Pulmonary Lymphangioleiomyomatosis
- Being tested
- saracatinib
- Keywords
- LAM
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
saracatinibDrug
Also called AZD0530
Subjects will receive enough tablets for 90 days +/- 14 days at each visit. Subject will have visits every 90 days for drug accountability as well as safety and efficacy testing to include pulmonary function testing, laboratory testing to include liver and kidney profile, urine pregnancy testing at each visit, vital signs, physical examination - any medically significant changes from baseline visit will be recorded, all adverse events will be monitored until resolution.
| Study group | Role | What they receive |
|---|---|---|
| Saracatinib | Experimental | Saracatinib will be given orally at a dose of 125 milligrams once daily for 9 months. Saracatinib is provided as a pink tablet. Receives: Drug: saracatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
FEV1
Measured: 9 months
Secondary outcomes (3)
Angiomyolipoma measured volumetrically on MRI
Measured: 12 months
Lung Cyst size measured on chest CT
Measured: 9 months
VEGF-D serum levels
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study startApr 2016
- Primary completion30 Jul 2019
- Study completion30 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Pulmonary LymphangioleiomyomatosisStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cincinnati, Brigham and Women's Hospital, Stanford University, Loyola University, University of South Florida, National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Nicola Hanania, Baylor College of Medicine
- Investigators
- Tony Eissa, MD, Study chair, Baylor College of MedicineNicola A Hanania, MD, Principal investigator, Ben Taub HospitalFrancis X McCormack, MD, Principal investigator, University of CincinnatiDaniel Dilling, MD, Principal investigator, Loyola UniversityStephen Ruoss, MD, Principal investigator, Stanford UniversityJoel Moss, MD, Principal investigator, Laboratory of Translational Research - NHLBI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02737202
- Sponsor's protocol ID
- SLAM 7602
- Other IDs
- 4UH3TR000961-02
- Acronym
- SLAM-2
- Status last verified
- Jul 2020
- First submitted
- 31 Mar 2016
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Young J, Povey S. The genetic basis of tuberous sclerosis. Mol Med Today. 1998 Jul;4(7):313-9. doi: 10.1016/s1357-4310(98)01245-3.
PubMed 9743993Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T, Hino O. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8762-7. doi: 10.1073/pnas.151033798. Epub 2001 Jul 3.
PubMed 11438694Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003 Jan;67(Pt 1):87-96. doi: 10.1046/j.1469-1809.2003.00012.x.
PubMed 12556239European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993 Dec 31;75(7):1305-15. doi: 10.1016/0092-8674(93)90618-z.
PubMed 8269512van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997 Aug 8;277(5327):805-8. doi: 10.1126/science.277.5327.805.
PubMed 9242607Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc. 2000 Jun;75(6):591-4. doi: 10.4065/75.6.591.
PubMed 10852420Franz DN, Brody A, Meyer C, Leonard J, Chuck G, Dabora S, Sethuraman G, Colby TV, Kwiatkowski DJ, McCormack FX. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001 Aug 15;164(4):661-8. doi: 10.1164/ajrccm.164.4.2011025.
PubMed 11520734Astrinidis A, Khare L, Carsillo T, Smolarek T, Au KS, Northrup H, Henske EP. Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis. J Med Genet. 2000 Jan;37(1):55-7. doi: 10.1136/jmg.37.1.55.
PubMed 10633137Illouz F, Braun D, Briet C, Schweizer U, Rodien P. Endocrine side-effects of anti-cancer drugs: thyroid effects of tyrosine kinase inhibitors. Eur J Endocrinol. 2014 Sep;171(3):R91-9. doi: 10.1530/EJE-14-0198. Epub 2014 May 15.
PubMed 24833135Neelakantan P, Rezvani K, May P, Gerrard G, Marco B, Paliompeis C, Reid A, Goldman J, Marin D, Milojkovic D. Excellent outcome after repeated changes of tyrosine kinase inhibitor therapy for chronic myeloid leukaemia in complete cytogenetic response due to minor side effects. Br J Haematol. 2014 Feb;164(4):608-10. doi: 10.1111/bjh.12648. Epub 2013 Nov 13. No abstract available.
PubMed 24219400Tyryshkin A, Bhattacharya A, Eissa NT. SRC kinase is a novel therapeutic target in lymphangioleiomyomatosis. Cancer Res. 2014 Apr 1;74(7):1996-2005. doi: 10.1158/0008-5472.CAN-13-1256.
PubMed 24691995Goncharova EA, Goncharov DA, Damera G, Tliba O, Amrani Y, Panettieri RA Jr, Krymskaya VP. Signal transducer and activator of transcription 3 is required for abnormal proliferation and survival of TSC2-deficient cells: relevance to pulmonary lymphangioleiomyomatosis. Mol Pharmacol. 2009 Oct;76(4):766-77. doi: 10.1124/mol.109.057042. Epub 2009 Jul 13.
PubMed 19596836Siemann DW, Dong M, Pampo C, Shi W. Src-signaling interference impairs the dissemination of blood-borne tumor cells. Cell Tissue Res. 2012 Aug;349(2):541-50. doi: 10.1007/s00441-012-1415-7. Epub 2012 Apr 18.
PubMed 22526632Dong M, Rice L, Lepler S, Pampo C, Siemann DW. Impact of the Src inhibitor saracatinib on the metastatic phenotype of a fibrosarcoma (KHT) tumor model. Anticancer Res. 2010 Nov;30(11):4405-13.
PubMed 21115886Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, Logie A, Hargreaves J, Hickinson DM, Wilkinson RW, Elvin P, Boyer B, Carragher N, Ple PA, Bermingham A, Holdgate GA, Ward WH, Hennequin LF, Davies BR, Costello GF. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol. 2009 Jun;3(3):248-61. doi: 10.1016/j.molonc.2009.01.002. Epub 2009 Feb 7.
PubMed 19393585
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis
- ClinicalTrials.gov ID
- NCT02737202
- Acronym / sponsor ID
- SLAM-2 / SLAM 7602
- Conditions
- Pulmonary Lymphangioleiomyomatosis
- Keywords
- LAM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- University of Cincinnati, Brigham and Women's Hospital, Stanford University, Loyola University, University of South Florida, National Institutes of Health (NIH)
- Study start
- Apr 2016 (actual)
- Primary completion
- 30 Jul 2019 (actual)
- Study completion
- 30 Jul 2019 (actual)
- First posted
- 13 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.
Detailed description
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 tumor suppressor genes. TSC is characterized by tumors in a wide range of tissues, seizures, mental retardation, autism, and organ failure. Lymphangioleiomyomatosis (LAM), the major pulmonary manifestation in women with TSC, is a progressive lung disease characterized by infiltration of atypical smooth muscle like cells (TSC-/- LAM cells) and formation of parenchymal cysts. Sporadic LAM can develop in women who do not meet the criteria for the diagnosis of TSC, owing to somatic mutations in the TSC2 gene.
The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation is reminiscent of cells undergoing epithelial-mesenchymal transition (EMT). Src kinases are key regulators of cellular proliferation, motility, invasiveness and EMT. Recent results have shown that autophagy promotes degradation of active Src. Thereby, decreased autophagy due to mTOR activation known to occur in LAM cells, may play a significant role in accumulation of active Src in these cells. Src suppresses transcription of E-cadherin by upregulating its transcriptional repressors. The preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in cultured TSC2-/- cells. Further, in TSC2-/- cells, E-cadherin is considerably reduced and does not localize to the plasma membrane, as it does in wild-type cells.
The focus of this study is to examine if Src inhibition represents a potential therapeutic strategy in LAM. It is proposed that Src activation in TSC2-/- cells results in the reduction of E-cadherin, loss of cell-cell adhesion and elevation of oncogenic and metastatic potential of these cells. The increased Src activity in TSC2-/- cells is likely caused by inhibition of autophagy associated with hyper-activation of mTOR. Therefore, the use of Src inhibitors may lead to a reduction in tumor growth and prevent dissemination of TSC2-/- cells. In this study, the investigators will evaluate the safety and efficacy of Src inhibition in subjects with LAM.
A number of inhibitors of Src are now in clinical trials in patients with a range of different tumors. Dasatinib, an oral adenosine triphosphate (ATP)-competitive Src inhibitor, is now approved for clinical use in patients with chronic myeloid leukemia or acute lymphoblastic leukemia. However, dasatinib has wider 'off target' inhibitory activity than saracatinib including potent activity against Abl, ephrin receptor kinases, platelet-derived growth factor receptor and c-KIT (type of receptor tyrosine kinase and a type of tumor marker. Also called CD117 and stem cell factor receptor.) In contrast, saracatinib has a >10-fold preference for Src over Abl kinases and has very little activity against other tyrosine and serine/threonine kinases. Saracatinib has been already characterized in multiple clinical trials in terms of safety and pharmacokinetics.
The investigators have conducted a Phase1b study to test the safety of various doses of Saracatinib in LAM subjects. The purpose of the Phase1b trial was to determine the optimal dose in terms of safety and tolerability in LAM population. Three escalating doses of saracatinib; 50, 125 and 175 mg were studied. Saracatinib was given orally once a day. Overall, subjects tolerated Saracatinib well. The investigators chose the dose of 125 mg to conduct further testing of both safety and efficacy in this Phase 2a trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Saracatinib | Experimental | Drug: saracatinibSaracatinib will be given orally at a dose of 125 milligrams once daily for 9 months. Saracatinib is provided as a pink tablet. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female patients. It should be noted that LAM occurs almost exclusively in women.
- 18 to 65 years of age.
- All patients must have a diagnosis of LAM as defined by compatible cystic changes on chest computed tomography (CT) and one of the following:
- Open lung, transbronchial or thoracic needle biopsy consistent with LAM
- Open or needle abdominal biopsy findings consistent with LAM
Key exclusion criteria (14 listed)
- Current infection.
- Major surgery within the past 2 months
- Advanced hematologic, renal, hepatic, non-LAM lung disease or metabolic diseases; or BMI of >35
- The use of another investigational drug within 30 days
- The use of mTOR (mammalian target of rapamycin) inhibitors within 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 |
|---|---|---|
| saracatinibAlso: AZD0530Subjects will receive enough tablets for 90 days +/- 14 days at each visit. Subject will have visits every 90 days for drug accountability as well as safety and efficacy testing to include pulmonary function testing, laboratory testing to include liver and kidney profile, urine pregnancy testing at each visit, vital signs, physical examination - any medically significant changes from baseline visit will be recorded, all adverse events will be monitored until resolution. | Drug | Saracatinib |
Primary outcome
FEV1
Time frame: 9 months
3 secondary outcomes
Angiomyolipoma measured volumetrically on MRI
Time frame: 12 months
Lung Cyst size measured on chest CT
Time frame: 9 months
VEGF-D serum levels
Time frame: 12 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Background: PubMed 9743993Young J, Povey S. The genetic basis of tuberous sclerosis. Mol Med Today. 1998 Jul;4(7):313-9. doi: 10.1016/s1357-4310(98)01245-3.
- Background: PubMed 11438694Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T, Hino O. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8762-7. doi: 10.1073/pnas.151033798. Epub 2001 Jul 3.
- Background: PubMed 12556239Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003 Jan;67(Pt 1):87-96. doi: 10.1046/j.1469-1809.2003.00012.x.
- Background: PubMed 8269512European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993 Dec 31;75(7):1305-15. doi: 10.1016/0092-8674(93)90618-z.
- Background: PubMed 9242607van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997 Aug 8;277(5327):805-8. doi: 10.1126/science.277.5327.805.
- Background: PubMed 10852420Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc. 2000 Jun;75(6):591-4. doi: 10.4065/75.6.591.
- Background: PubMed 11520734Franz DN, Brody A, Meyer C, Leonard J, Chuck G, Dabora S, Sethuraman G, Colby TV, Kwiatkowski DJ, McCormack FX. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001 Aug 15;164(4):661-8. doi: 10.1164/ajrccm.164.4.2011025.
- Background: PubMed 10633137Astrinidis A, Khare L, Carsillo T, Smolarek T, Au KS, Northrup H, Henske EP. Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis. J Med Genet. 2000 Jan;37(1):55-7. doi: 10.1136/jmg.37.1.55.
- Background: PubMed 24833135Illouz F, Braun D, Briet C, Schweizer U, Rodien P. Endocrine side-effects of anti-cancer drugs: thyroid effects of tyrosine kinase inhibitors. Eur J Endocrinol. 2014 Sep;171(3):R91-9. doi: 10.1530/EJE-14-0198. Epub 2014 May 15.
- Background: PubMed 24219400Neelakantan P, Rezvani K, May P, Gerrard G, Marco B, Paliompeis C, Reid A, Goldman J, Marin D, Milojkovic D. Excellent outcome after repeated changes of tyrosine kinase inhibitor therapy for chronic myeloid leukaemia in complete cytogenetic response due to minor side effects. Br J Haematol. 2014 Feb;164(4):608-10. doi: 10.1111/bjh.12648. Epub 2013 Nov 13. No abstract available.
- Background: PubMed 24691995Tyryshkin A, Bhattacharya A, Eissa NT. SRC kinase is a novel therapeutic target in lymphangioleiomyomatosis. Cancer Res. 2014 Apr 1;74(7):1996-2005. doi: 10.1158/0008-5472.CAN-13-1256.
- Background: PubMed 19596836Goncharova EA, Goncharov DA, Damera G, Tliba O, Amrani Y, Panettieri RA Jr, Krymskaya VP. Signal transducer and activator of transcription 3 is required for abnormal proliferation and survival of TSC2-deficient cells: relevance to pulmonary lymphangioleiomyomatosis. Mol Pharmacol. 2009 Oct;76(4):766-77. doi: 10.1124/mol.109.057042. Epub 2009 Jul 13.
- Individual participant dataSharing planned: No
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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.
Tony Eissa, MD study chair
Baylor College of Medicine
Nicola A Hanania, MD principal investigator
Ben Taub Hospital
Francis X McCormack, MD principal investigator
University of Cincinnati
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing saracatinib in people with Pulmonary Lymphangioleiomyomatosis, run by Baylor College of Medicine at 5 sites 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 8 inclusion and 14 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: stopped early, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
The study was stopped early. Results are not available in the source record.
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?
FEV1 (time frame: 9 months). 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 NCT02737202, which also lists 39 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 Jul 2020.