Estrogen Receptor-positive Breast CancerPhase 2NCT02273752
Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer
A Phase 2 study testing Everolimus in people with Estrogen Receptor-positive Breast Cancer and Gastrinoma, run by Emory University at 2 sites in United States.
Trial summary
This phase II trial studies how well real-time pharmacokinetic therapeutic drug monitoring works in preventing stomatitis from developing in patients with hormone receptor positive breast cancer, pancreatic neuroendocrine tumors, or kidney cancer that are receiving a type of cancer drug called everolimus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer, Gastrinoma, Glucagonoma
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2014to Dec 2015
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Confirmed diagnosis of:
- Postmenopausal advanced hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer after failure of treatment with letrozole or anastrozole
- Progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic
- Advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib
- Histologically confirmed, measurable or evaluable disease. Patients should have at least one measurable lesion.
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- Adequate bone marrow function as indicated by the following:
- Absolute neutrophil count (ANC) > 1,500/μL
- Platelets ≥ 100,000/μL
- Hemoglobin > 10 g/dL
- Adequate renal function, as indicated by creatinine clearance > 30 mL/min
- Adequate liver function, as indicated by:
- Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- International normalized ratio (INR) ≤ 2
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x ULN unless related to primary disease
- Signed informed consent
- Adequate birth control when appropriate
- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
Who cannot join
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc., but not including somatostatin analogues, e.g., octreotide)
- Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
- Patients who have any severe and/or uncontrolled medical conditions such as:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
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- Symptomatic congestive heart failure of New York Heart Association Class III or IV
- Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-DNA and/or positive HbsAg, quantifiable hepatitis C virus [HCV]-RNA)
- Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and O2 saturation 88% or less at rest on room air)
- Active, bleeding diathesis
- Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed.
- Known history of HIV seropositivity
- Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines.
- Patients who have a history of another primary malignancy, with the exceptions of: nonmelanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for ≥3 years
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
- Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
- Pregnant or nursing (lactating) women
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include combination of any two of the following:
- Use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
- Total abstinence
- Male/female sterilization
- Women are considered post-menopausal and not of child-bearing 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 child-bearing potential.
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Phase II Evaluation of Real-Time, Pharmacokinetically Guided Everolimus in Patients With Hormone Receptor Positive Breast Cancer, Pancreatic Neuroendocrine Tumors (PNET), and Renal Cell Carcinoma
This phase II trial studies how well real-time pharmacokinetic therapeutic drug monitoring works in preventing stomatitis from developing in patients with hormone receptor positive breast cancer, pancreatic neuroendocrine tumors, or kidney cancer that are receiving a type of cancer drug called everolimus. Stomatitis is a common side effect of everolimus that causes inflammation of the mouth, with or without oral ulcers, and frequently leads to patients discontinuing the medication. Monitoring the blood levels of everolimus and making adjustments in a patient's dose may be able to decrease the incidence of stomatitis, while maintaining the effectiveness of everolimus to treat the cancer.
Read the detailed description
PRIMARY OBJECTIVE:
To determine frequency of any grade of stomatitis at day 29 (cycle 2, day 1) in patients receiving dose-adjusted everolimus.
SECONDARY OBJECTIVES:
- Progression-free survival rates at 6 months.
- Pharmacodynamic (PD)-inhibition of downstream mammalian target of rapamycin (mTOR) effectors in peripheral blood.
- Number of dose adjustments required.
- Percentage of days on therapy.
- Average minimum concentration (Cmin) values.
- Frequency and type of treatments for stomatitis.
- Genetic predictors of stomatitis development in selected outlier patients.
OUTLINE:
Patients receive everolimus orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic therapeutic drug monitoring (TDM) on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6.
After completion of study treatment, patients are followed up every 12 weeks.
- Conditions
- Estrogen Receptor-positive Breast Cancer, Gastrinoma, Glucagonoma, HER2-negative Breast Cancer, Insulinoma, Mucositis
- Being tested
- Everolimus
- Medical subject headings
- Gastrinoma, Glucagonoma, Insulinoma, Mucositis, Breast Neoplasms, Carcinoma, Islet Cell, Carcinoma, Renal Cell, Somatostatinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Supportive care (real-time pharmacokinetic TDM of everolimus) | Experimental | Patients receive everolimus PO daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic TDM on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Stomatitis
Stomatitis graded rates and severity will be evaluated and recorded per World Health Organization and Common Terminology Criteria for Adverse Events criteria in the study population.
Measured: Day 29
Secondary outcomes (7)
Progression Free Survival (PFS)
PFS will be evaluated based on rates of cancer progression and time to progression in the population. Progression will be determined using standard RECIST criteria. The median PFS for this study will be estimated by Kaplan-Meier method along with 95% confidence interval.
Measured: 6 months
Downstream Markers of Mammalian Target of Rapamycin (mTOR) Function Measured in Peripheral Blood Mononuclear Cells
Pharmacodynamics will be evaluated for phosphorylated and non-phosphorylated ribosomal protein S6 kinase, protein kinase B, and eukaryotic translation initiation factor 4E-binding protein 1.
Measured: Up to day 15 of course 1
Percentage of Days on Therapy
Percentage of days on therapy will be calculated using the formula: (expected - actual days)/expected x 100.
Measured: Up to 6 months
Dose Interruptions and Adjustments
Dose interruptions and adjustments will be made on a per subject basis and total for the population.
Measured: Up to 6 months
Frequency of Treatments for Stomatitis
Frequency of treatments for stomatitis will be collection of prescription and non-prescription interventions.
Measured: Up to 6 months
Type of Treatments for Stomatitis
Type of treatments for stomatitis will be collection of prescription and non-prescription interventions.
Measured: Up to 6 months
Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Response rate will be measured at different time points, e.g. 8, 16, and 24 weeks, and will be summarized as percentage of stable disease, complete remission or partial remission along with 95% confidence interval.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: Slow accrual
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 Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, R. Donald Harvey, PharmD, Emory University
- Investigators
- R. Donald Harvey, PharmD, Principal investigator, Emory University/Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02273752
- Sponsor's protocol ID
- IRB00072091
- Other IDs
- NCI-2014-02112, WINSHIP2645-14
- Status last verified
- Dec 2016
- First submitted
- 22 Oct 2014
- Last updated
- 3 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Evaluation of Real-Time, Pharmacokinetically Guided Everolimus in Patients With Hormone Receptor Positive Breast Cancer, Pancreatic Neuroendocrine Tumors (PNET), and Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02273752
- Acronym / sponsor ID
- IRB00072091
- Conditions
- Estrogen Receptor-positive Breast Cancer, Gastrinoma, Glucagonoma, HER2-negative Breast Cancer, Insulinoma, Mucositis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Nov 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 24 Oct 2014 (estimated)
- Results
- Posted 3 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well real-time pharmacokinetic therapeutic drug monitoring works in preventing stomatitis from developing in patients with hormone receptor positive breast cancer, pancreatic neuroendocrine tumors, or kidney cancer that are receiving a type of cancer drug called everolimus. Stomatitis is a common side effect of everolimus that causes inflammation of the mouth, with or without oral ulcers, and frequently leads to patients discontinuing the medication. Monitoring the blood levels of everolimus and making adjustments in a patient's dose may be able to decrease the incidence of stomatitis, while maintaining the effectiveness of everolimus to treat the cancer.
Detailed description
PRIMARY OBJECTIVE:
To determine frequency of any grade of stomatitis at day 29 (cycle 2, day 1) in patients receiving dose-adjusted everolimus.
SECONDARY OBJECTIVES:
- Progression-free survival rates at 6 months.
- Pharmacodynamic (PD)-inhibition of downstream mammalian target of rapamycin (mTOR) effectors in peripheral blood.
- Number of dose adjustments required.
- Percentage of days on therapy.
- Average minimum concentration (Cmin) values.
- Frequency and type of treatments for stomatitis.
- Genetic predictors of stomatitis development in selected outlier patients.
OUTLINE:
Patients receive everolimus orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic therapeutic drug monitoring (TDM) on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6.
After completion of study treatment, patients are followed up every 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Supportive care (real-time pharmacokinetic TDM of everolimus) | Experimental | Drug: EverolimusPatients receive everolimus PO daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic TDM on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Confirmed diagnosis of:
- Histologically confirmed, measurable or evaluable disease. Patients should have at least one measurable lesion.
- Adequate bone marrow function as indicated by the following:
- Adequate renal function, as indicated by creatinine clearance > 30 mL/min
Key exclusion criteria (25 listed)
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc., but not including somatostatin analogues, e.g., octreotide)
- Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
- Patients who have any severe and/or uncontrolled medical conditions such as:
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: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Given PO | Drug | Supportive care (real-time pharmacokinetic TDM of everolimus) |
Primary outcome
Incidence of Stomatitis
Time frame: Day 29
Stomatitis graded rates and severity will be evaluated and recorded per World Health Organization and Common Terminology Criteria for Adverse Events criteria in the study population.
7 secondary outcomes
Progression Free Survival (PFS)
Time frame: 6 months
Downstream Markers of Mammalian Target of Rapamycin (mTOR) Function Measured in Peripheral Blood Mononuclear Cells
Time frame: Up to day 15 of course 1
Percentage of Days on Therapy
Time frame: Up to 6 months
Dose Interruptions and Adjustments
Time frame: Up to 6 months
Frequency of Treatments for Stomatitis
Time frame: Up to 6 months
Type of Treatments for Stomatitis
Time frame: Up to 6 months
Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Time frame: Up to 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
R. Donald Harvey, PharmD principal investigator
Emory University/Winship Cancer Institute
2 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 Everolimus in people with Estrogen Receptor-positive Breast Cancer and Gastrinoma, run by Emory University at 2 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 18 inclusion and 25 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 3 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 3 Feb 2017). 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?
Incidence of Stomatitis (time frame: Day 29). 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 3 Feb 2017.