Solid MalignancyPhase 2NCT02352844
Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations
A Phase 2 study testing Everolimus in people with Solid Malignancy and Solid Tumor, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this research study is to look at participants with solid tumor malignancies and specific mutations respond to treatment with everolimus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Malignancy, Solid Tumor
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2015to 15 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of advanced (metastatic, recurrent, or unresectable) cancer with mutations in any of the following genes: TSC1, TSC2, NF1, NF2 or STK11.
- Must have failed at least 1 standard of care systemic therapy for their malignancy
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam.
- Prior therapy (chemotherapy, radiation therapy, and surgery) is allowed if completed at least 2 weeks prior to registration and if all treatment-related toxicities are resolved to ≤ CTCAE grade 1, with the exception of alopecia and hematologic values otherwise meeting the bone marrow function criteria specified below.
- At least 18 years of age.
- ECOG performance status ≤ 2
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- Normal bone marrow and organ function as defined below:
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Hemoglobin > 9.0 g/dL
- Total serum bilirubin ≤ 2.0 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (≤ 5.0 x IULN in patients with liver metastases)
- Serum creatinine ≤ 1.5 x IULN OR creatinine clearance > 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Fasting cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x IULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- Able to swallow tablets.
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and for 8 weeks after. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
- Male patients whose sexual partner(s) are women of childbearing potential must agree to use adequate contraception during the study and for 8 weeks after the end of treatment.
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)
Who cannot join
- A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Taking an investigational agent within 4 weeks of initiation of everolimus.
- Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or other agents used in the study.
- Known impairment of GI function or GI disease that may significantly alter the absorption of oral everolimus.
- Currently taking CYP3A4 inhibitors or inducers (such as the antiepileptic drugs phenytoin, carbamazepine, or phenobarbital; cyclosporine; grapefruit or its juice; Seville oranges; starfruit; or St. John's wort)
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- Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed.
- Received live attenuated vaccine within 1 week of start of everolimus (i.e. intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines).
- Uncontrolled diabetes mellitus defined as HbA1c > 8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus may be included; however, blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure of NYHA class III or IV, active coronary artery disease, unstable angina pectoris, cardiac arrhythmia, myocardia infraction ≤ 6 months prior to start of everolimus, uncontrolled hypertension (systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg), uncontrolled seizure disorder, liver disease such as cirrhosis, decompensated liver disease, active and chronic hepatitis, known severely impaired lung function (spirometry and DLCO 50% or less of normal and 02 saturation 88% or less at rest on room air), active bleeding diathesis, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with everolimus. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase II Study of Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations
The purpose of this research study is to look at participants with solid tumor malignancies and specific mutations respond to treatment with everolimus.
Read the detailed description
Cancer is a molecularly heterogeneous disease comprised of complex genomic alterations in common and overlapping pathways. Somatic inactivating mutations in tuberous sclerosis complex 1 (TSC1) gene were recently identified as potential markers of response to mTOR therapy. Everolimus is an oral derivative of rapamycin. At the cellular and molecular level, everolimus acts as a signal transduction inhibitor, and selectively inhibits mTOR. We hypothesize that everolimus will exhibit clinical activity in solid malignancies harboring TSC1, TSC2, NF1, NF2, or STK11 mutations.
- Conditions
- Solid Malignancy, Solid Tumor
- Being tested
- Everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001, Afinitor, Votubia
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (everolimus) | Experimental | Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (RR)
The primary endpoint will be to describe the response rate using RECIST 1.1. Response rate will be defined as complete response (disappearance of all target lesion) plus partial response (a least a 30% decrease in the sum of diameters of target lesions).
Measured: Completion of treatment (estimated average of 6 months)
Secondary outcomes (2)
Mutations Associated With Therapeutic Response
-To correlate mutations in the mTOR pathway with therapeutic response with everolimus
Measured: Completion of treatment (estimated average of 6 months)
Genetic Changes Associated With Disease Progression
-To investigate the genetic changes associated with disease progression following treatment with everolimus.
Measured: Completion of treatment (estimated average of 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study start7 Oct 2015
- Primary completion15 Aug 2017
- Study completion15 Aug 2017
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.
- Other trials for Solid MalignancyStudies of the same condition, open and under way.
- More trials run by Washington University School 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saiama Waqar, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02352844
- Sponsor's protocol ID
- 201502067
- Status last verified
- Sep 2018
- First submitted
- 28 Jan 2015
- Last updated
- 2 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations
- ClinicalTrials.gov ID
- NCT02352844
- Acronym / sponsor ID
- 201502067
- Conditions
- Solid Malignancy, Solid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 7 Oct 2015 (actual)
- Primary completion
- 15 Aug 2017 (actual)
- Study completion
- 15 Aug 2017 (actual)
- First posted
- 2 Feb 2015 (estimated)
- Results
- Posted 2 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to look at participants with solid tumor malignancies and specific mutations respond to treatment with everolimus.
Detailed description
Cancer is a molecularly heterogeneous disease comprised of complex genomic alterations in common and overlapping pathways. Somatic inactivating mutations in tuberous sclerosis complex 1 (TSC1) gene were recently identified as potential markers of response to mTOR therapy. Everolimus is an oral derivative of rapamycin. At the cellular and molecular level, everolimus acts as a signal transduction inhibitor, and selectively inhibits mTOR. We hypothesize that everolimus will exhibit clinical activity in solid malignancies harboring TSC1, TSC2, NF1, NF2, or STK11 mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (everolimus) | Experimental | Drug: EverolimusEverolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed diagnosis of advanced (metastatic, recurrent, or unresectable) cancer with mutations in any of the following genes: TSC1, TSC2, NF1, NF2 or STK11.
- Must have failed at least 1 standard of care systemic therapy for their malignancy
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam.
- Prior therapy (chemotherapy, radiation therapy, and surgery) is allowed if completed at least 2 weeks prior to registration and if all treatment-related toxicities are resolved to ≤ CTCAE grade 1, with the exception of alopecia and hematologic values otherwise meeting the bone marrow function criteria specified below.
- At least 18 years of age.
Key exclusion criteria (12 listed)
- A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Taking an investigational agent within 4 weeks of initiation of everolimus.
- Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or other agents used in the study.
- Known impairment of GI function or GI disease that may significantly alter the absorption of oral everolimus.
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 |
|---|---|---|
| EverolimusAlso: RAD001, Afinitor, Votubia | Drug | Arm 1 (everolimus) |
Primary outcome
Response Rate (RR)
Time frame: Completion of treatment (estimated average of 6 months)
The primary endpoint will be to describe the response rate using RECIST 1.1. Response rate will be defined as complete response (disappearance of all target lesion) plus partial response (a least a 30% decrease in the sum of diameters of target lesions).
2 secondary outcomes
Mutations Associated With Therapeutic Response
Time frame: Completion of treatment (estimated average of 6 months)
Genetic Changes Associated With Disease Progression
Time frame: Completion of treatment (estimated average of 6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Saiama Waqar, M.D. principal investigator
Washington University School of Medicine
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 Everolimus in people with Solid Malignancy and Solid Tumor, run by Washington University School of Medicine 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 19 inclusion and 12 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 2 Oct 2018. 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 2 Oct 2018). 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?
Response Rate (RR) (time frame: Completion of treatment (estimated average of 6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2018.