Nonmalignant NeoplasmPhase 2NCT00126672
RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS
A Phase 2 study testing Rapamycin in people with Nonmalignant Neoplasm and Tuberous Sclerosis, run by Dana-Farber Cancer Institute at 7 sites in United States.
Trial summary
This research study is evaluating a drug called rapamycin as a possible treatment for the lumps (or tumors) that form in the kidneys, called angiomyolipomas, in people who have either TSC or LAM. Kidney angiomyolipomas are tumors that are made up of blood vessels, muscle and fat. Read more about this study
- Who is it for?
- Ages 3 to 65 years
- Conditions the study is for
- Nonmalignant Neoplasm, Tuberous Sclerosis, Lymphangioleimyomatosis
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 7 sitesUnited States
- Study dates
- 20 Dec 2005to Apr 2010
- 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 3-65 years old (females of reproductive age must not be pregnant or breastfeeding)
- Kidney ANGIOMYOLIPOMA 2 cm or greater on baseline MRI (a CT scan may be used for patients who cannot undergo MRI imaging)
- No evidence of severe LAM (not on continuous oxygen)
- Informed consent, including consent for submission of blood, urine and tissue samples as described in the appendix.
- Adequate renal and liver function (eGFR of 30 or higher, SGOT, SGPT, TBili, Alk Phos all<2x normal)
- HCT>27%
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- ANC > 1500 and platelet count >100,000
- Diagnosis of TSC or LAM (diagnosis of TSC using revised diagnostic criteria [45], diagnosis of LAM made by chest CT scan and reviewed by a pulmonologist).
- Fertility/Reproductive issues: The effects of rapamycin on the developing fetus at the doses used in this study are unknown. For this reason, rapamycin should not be taken during pregnancy. Participants who are fertile must maintain adequate contraception while they are taking rapamycin and for twelve weeks after stopping the drug. Acceptable contraceptive measures include prior hysterectomy, oophorectomy or tubal ligation, complete abstinence, barrier methods which include both a cervical diaphragm and spermicidal jelly, and progestin based contraceptives. Pregnancy tests will be obtained at enrollment and during study visits at 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, and 52 weeks.
- Note: Eligibility requirement of ECOG PS of 0 or 1 has been removed to allow participation of those subjects with TSC who are classified as ECOG PS of 2,3, or 4 because of cognitive impairment rather than progressive disease. This change allows site Pl's to individualize decision making on whether or not to enroll such subjects after discussing details of the study with prospective participant and legal guardian. The decision to enroll individuals with ECOG PS of 2,3, or 4 will be at the discretion of the Principal Investigator.
Who cannot join
- Unstable seizures (defined as changes in anti-epileptics OR increase in frequency and/or severity or seizures in the 60 days prior to study entry)
- Significant bleed associated with kidney angiomyolipoma(s) (defined as bleed associated with shock OR requiring a blood transfusion in the 30 days prior to study entry)
- Severe LAM (defined as dependent on continuous supplemental oxygen)
- Evidence for accelerating renal dysfunction or acute renal failure
- Diagnosis of Renal Cell Cancer that has not been treated (additional clarification: individuals with a prior history of renal cancer who have had appropriate surgery and have no evidence of metastatic disease can be enrolled)
- Active infection
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- Patients will be excluded if they have been treated with any investigational agent in the 30 days prior to study entry
- Patients may not be treated with other investigational agents while on study
- Prior history of coronary artery disease
- Vascular embolization for treatment of kidney angiomyolipoma(s) within 6 months
- Patients who must take diltiazem, ketoconazole or rifampin chronically will be excluded because of known drug interactions. Both diltiazem and ketoconazole are strong inhibitors of CYP3A4 and are known to increase rapamycin levels. Rifampin is a known CYP3A4 and P-glycoprotein inducer and is known to significantly reduce rapamycin levels.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Loma Linda University School of Medicine
Loma Linda, California, 92350
New York University Medical Center
New York, New York, 10016
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase II Multi-Center Study of Rapamycin for Treating Kidney Angiomyolipomas in TSC or LAM Patients
This research study is evaluating a drug called rapamycin as a possible treatment for the lumps (or tumors) that form in the kidneys, called angiomyolipomas, in people who have either TSC or LAM. Kidney angiomyolipomas are tumors that are made up of blood vessels, muscle and fat. Rapamycin has been approved to treat other diseases, but it is investigational for treating kidney angiomyolipomas.
Investigational means that it is being as a possible treatment for kidney angiomyolipomas but is not currently approved by the U.S. Food and Drug Administration (FDA) for treating this disease.
Read the detailed description
This research study is a Phase ll clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of diseases. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved this drug for this type of disease.
The purpose of this research study is to see if the drug, rapamycin, is effective in treating kidney angiomyolipomas. Rapamycin is a drug that may decrease the size of tumors. This drug has been used in treating other diseases and cancers in humans and information from those other research studies suggests that rapamycin may help to shrink tumors in this research study.
The investigators will also be looking at the safety of this drug in people with TSC or LAM. In addition, the investigators will also look at whether this drug is effective for treating other conditions that occur in people that have TSC or LAM (tubers, subependymal giant cell astrocytomos, facial angiofibromas, kidney cysts in TSC, or symptoms of cough, breathing trouble or other symptoms of lung problems in people with LAM).
Although these tumors (kidney angiomyolipomas) may not change for many years, they do not go away on their own. They often grow larger and may bleed. The standard of care for treating these tumors is to take pictures of them using ultrasound, CT or MRI (called kidney imaging) every 1-3 years to see if they are getting larger or if they are bleeding. If they do grow larger or bleed, removing them by surgery or cutting off the blood supply to the tumor (vascular embolization) may be recommended.
This research study is being done because there are no medicines available at this time that can treat kidney angiomyolipomas. However, recent studies in the laboratory have shown that the drug, rapamycin, maybe effective in treating these tumors. Because rapamycin is approved by the FDA for treating other medical conditions, we know what doses are safe to use based on guidelines that have been approved by the FDA.
- Being tested
- Rapamycin
- Keywords
- angiomyolipoma
- Medical subject headings
- Neoplasms, Tuberous Sclerosis, Angiomyolipoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Rapamune, Sirolimus
| Study group | Role | What they receive |
|---|---|---|
| Ramaycin | Experimental | Rapamycin treatment was initiated with a loading dose of 6 mg by mouth on day 1 followed by 2 mg by mouth daily. The dose was then adjusted to maintain a target blood level of 3-9 ng/ml for the first 16 weeks. After week 16, the dose of Rapamycin was increased to a target level of 9-15 ng/ml unless there was evidence for a partial response or complete response by kidney MRI. Trough Rapamycin levels were checked every 8-12 weeks (at 24 weeks, 32 weeks, 40 weeks, and 52 weeks) in all patients until the 12-month (week 52) study visit. If the Rapamycin dose was below target, the dose was increased by 1-2 mg until the target trough level was achieved. Rapamycin levels were checked every 2-3 weeks while the dose was adjusted. Amendment 20 (Jan 2009) permitted additional Rapamycin treatment during months 12-24 if the treating site investigator judged that this was in the best interest of the study participant. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks.
Secondary outcomes (2)
Number of Participants With Grade 3 or More Treatment-Related Lymphopenia
All participants reporting maximum grade 3 or more lymphopenia adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 on case report forms were counted.
Measured: Assessed on treatment up to 52 weeks.
Number of Participants With no Change Are Observed Changes That Occur in Other TSC Lesions
TSC lesions are tubers, subependymal giant cell astrocytomas, facial angiofibromas, kidney cysts.
Measured: Data collected at week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2005 (estimated)
- Study start20 Dec 2005
- Primary completionApr 2010
- Study completionApr 2010
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 (2)Papers the sponsor has linked to this study.
- Other trials for Nonmalignant NeoplasmStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Wyeth is now a wholly owned subsidiary of Pfizer, Tuberous Sclerosis Alliance
- Responsible party
- Sponsor
- Investigators
- Sandra Dabora, MD, PhD, Principal investigator, Dana-Farber/Brigham and Women's Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00126672
- Sponsor's protocol ID
- 04-298
- Other IDs
- R01CA107164, P30CA006516
- Status last verified
- Mar 2022
- First submitted
- 2 Aug 2005
- Last updated
- 25 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Malinowska IA, Lee N, Kumar V, Thiele EA, Franz DN, Ashwal S, Sagalowsky A, Dimario FJ Jr, Cutler D, Krueger D, Camposano S, Paolini J, Dabora SL. Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis. PLoS One. 2013;8(2):e56199. doi: 10.1371/journal.pone.0056199. Epub 2013 Feb 20.
PubMed 23437092Dabora SL, Franz DN, Ashwal S, Sagalowsky A, DiMario FJ Jr, Miles D, Cutler D, Krueger D, Uppot RN, Rabenou R, Camposano S, Paolini J, Fennessy F, Lee N, Woodrum C, Manola J, Garber J, Thiele EA. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS One. 2011;6(9):e23379. doi: 10.1371/journal.pone.0023379. Epub 2011 Sep 6.
PubMed 21915260
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multi-Center Study of Rapamycin for Treating Kidney Angiomyolipomas in TSC or LAM Patients
- ClinicalTrials.gov ID
- NCT00126672
- Acronym / sponsor ID
- 04-298
- Keywords
- angiomyolipoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Wyeth is now a wholly owned subsidiary of Pfizer, Tuberous Sclerosis Alliance
- Study start
- 20 Dec 2005 (actual)
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 4 Aug 2005 (estimated)
- Results
- Posted 25 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is evaluating a drug called rapamycin as a possible treatment for the lumps (or tumors) that form in the kidneys, called angiomyolipomas, in people who have either TSC or LAM. Kidney angiomyolipomas are tumors that are made up of blood vessels, muscle and fat. Rapamycin has been approved to treat other diseases, but it is investigational for treating kidney angiomyolipomas.
Investigational means that it is being as a possible treatment for kidney angiomyolipomas but is not currently approved by the U.S. Food and Drug Administration (FDA) for treating this disease.
Detailed description
This research study is a Phase ll clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of diseases. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved this drug for this type of disease.
The purpose of this research study is to see if the drug, rapamycin, is effective in treating kidney angiomyolipomas. Rapamycin is a drug that may decrease the size of tumors. This drug has been used in treating other diseases and cancers in humans and information from those other research studies suggests that rapamycin may help to shrink tumors in this research study.
The investigators will also be looking at the safety of this drug in people with TSC or LAM. In addition, the investigators will also look at whether this drug is effective for treating other conditions that occur in people that have TSC or LAM (tubers, subependymal giant cell astrocytomos, facial angiofibromas, kidney cysts in TSC, or symptoms of cough, breathing trouble or other symptoms of lung problems in people with LAM).
Although these tumors (kidney angiomyolipomas) may not change for many years, they do not go away on their own. They often grow larger and may bleed. The standard of care for treating these tumors is to take pictures of them using ultrasound, CT or MRI (called kidney imaging) every 1-3 years to see if they are getting larger or if they are bleeding. If they do grow larger or bleed, removing them by surgery or cutting off the blood supply to the tumor (vascular embolization) may be recommended.
This research study is being done because there are no medicines available at this time that can treat kidney angiomyolipomas. However, recent studies in the laboratory have shown that the drug, rapamycin, maybe effective in treating these tumors. Because rapamycin is approved by the FDA for treating other medical conditions, we know what doses are safe to use based on guidelines that have been approved by the FDA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ramaycin | Experimental | Drug: RapamycinRapamycin treatment was initiated with a loading dose of 6 mg by mouth on day 1 followed by 2 mg by mouth daily. The dose was then adjusted to maintain a target blood level of 3-9 ng/ml for the first 16 weeks. After week 16, the dose of Rapamycin was increased to a target level of 9-15 ng/ml unless there was evidence for a partial response or complete response by kidney MRI. Trough Rapamycin levels were checked every 8-12 weeks (at 24 weeks, 32 weeks, 40 weeks, and 52 weeks) in all patients until the 12-month (week 52) study visit. If the Rapamycin dose was below target, the dose was increased by 1-2 mg until the target trough level was achieved. Rapamycin levels were checked every 2-3 weeks while the dose was adjusted. Amendment 20 (Jan 2009) permitted additional Rapamycin treatment during months 12-24 if the treating site investigator judged that this was in the best interest of the study participant. |
Who may qualify
- Ages
- 3 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age 3-65 years old (females of reproductive age must not be pregnant or breastfeeding)
- Kidney ANGIOMYOLIPOMA 2 cm or greater on baseline MRI (a CT scan may be used for patients who cannot undergo MRI imaging)
- No evidence of severe LAM (not on continuous oxygen)
- Informed consent, including consent for submission of blood, urine and tissue samples as described in the appendix.
- Adequate renal and liver function (eGFR of 30 or higher, SGOT, SGPT, TBili, Alk Phos all<2x normal)
Key exclusion criteria (11 listed)
- Unstable seizures (defined as changes in anti-epileptics OR increase in frequency and/or severity or seizures in the 60 days prior to study entry)
- Significant bleed associated with kidney angiomyolipoma(s) (defined as bleed associated with shock OR requiring a blood transfusion in the 30 days prior to study entry)
- Severe LAM (defined as dependent on continuous supplemental oxygen)
- Evidence for accelerating renal dysfunction or acute renal failure
- Diagnosis of Renal Cell Cancer that has not been treated (additional clarification: individuals with a prior history of renal cancer who have had appropriate surgery and have no evidence of metastatic disease can be enrolled)
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 |
|---|---|---|
| RapamycinAlso: Rapamune, Sirolimus | Drug | Ramaycin |
Primary outcome
Objective Response Rate
Time frame: On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks.
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
2 secondary outcomes
Number of Participants With Grade 3 or More Treatment-Related Lymphopenia
Time frame: Assessed on treatment up to 52 weeks.
Number of Participants With no Change Are Observed Changes That Occur in Other TSC Lesions
Time frame: Data collected at week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23437092Malinowska IA, Lee N, Kumar V, Thiele EA, Franz DN, Ashwal S, Sagalowsky A, Dimario FJ Jr, Cutler D, Krueger D, Camposano S, Paolini J, Dabora SL. Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis. PLoS One. 2013;8(2):e56199. doi: 10.1371/journal.pone.0056199. Epub 2013 Feb 20.
- Derived from this study: PubMed 21915260Dabora SL, Franz DN, Ashwal S, Sagalowsky A, DiMario FJ Jr, Miles D, Cutler D, Krueger D, Uppot RN, Rabenou R, Camposano S, Paolini J, Fennessy F, Lee N, Woodrum C, Manola J, Garber J, Thiele EA. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS One. 2011;6(9):e23379. doi: 10.1371/journal.pone.0023379. Epub 2011 Sep 6.
- 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.
Sandra Dabora, MD, PhD principal investigator
Dana-Farber/Brigham and Women's Cancer Center
7 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 Rapamycin in people with Nonmalignant Neoplasm and Tuberous Sclerosis, run by Dana-Farber Cancer Institute at 7 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 10 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 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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?
Yes. Results are posted in the registry (first posted 25 Apr 2022). 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?
Objective Response Rate (time frame: On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks.). 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 NCT00126672, which also lists 2 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 25 Apr 2022.