Metastatic MelanomaPhase 2NCT00402662
A Study of Everolimus in Combination With Imatinib in Metastatic Melanoma
A Phase 2 study testing everolimus and Imatinib in people with Metastatic Melanoma, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to determine if the combination of everolimus and imatinib will slow the growth of or cause a reduction in the size of the cancer, and to determine the side effects of the combination in patients with melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- everolimus and Imatinib
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Jun 2006
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed stage III unresectable or stage IV metastatic melanoma. Patients must have measurable disease as defined by RECIST criteria.
- Patients with up to 1 prior cytotoxic regimen for metastatic disease will be eligible. There will be no prior limitation on adjuvant therapies for stage II/III disease or for patients with stage IV disease treated after resection of all metastatic disease. There will be no prior limitation on biological or hormonal therapies (immune therapies, interferon, hypomethylating agents, histone deacetylase inhibitors, etc.), however, patients previously treated with mTOR inhibitors will be excluded. Prior treatment for metastatic disease is not required. Patients must have recovered from the acute toxicities of prior treatment. Chronic toxicities must have recovered to ≤ grade 1. The minimum interval between prior treatment and first day of dosing on this trial is as follows: standard cytotoxic agents and radiation therapy, 21 days; mitomycin and nitrosoureas, 6 weeks; hormonal and immunotherapy agents, 2 weeks; minor surgery, 2 weeks, major surgery, 3 weeks; investigational agents 4-weeks.
- Age >18 years. Because no dosing or adverse event data are currently available on the use of everolimus in combination with imatinib in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
- ECOG performance status < 1.
- Life expectancy of greater than 3 months.
- Patients must have organ and marrow function as defined below:
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- Leukocytes >3,000/μL; Absolute neutrophil count >1,500/ μL; platelets >100,000/ μL; Hemoglobin ≥ 9.0 gm/dL (may be transfused to this level); PT/PTT < 1.5x upper limit of normal; Total bilirubin ≤ 2.0 mg/dL;AST(SGOT)/ALT(SGPT) <3X institutional upper limit of normal; Creatinine ≤ 2.0 mg/dL or creatinine clearance >50 mL/min/1.73m2
- The effects of everolimus and imatinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 3 months after stopping study drug. Should a woman (or the partner of a man participating in this trial) become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients may not be receiving any other investigational agents. Patients may not have received prior treatment for their cancer with an mTOR inhibitor.
- Patients with known brain metastases or leptomeningeal disease are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with previously treated brain metastases, who no longer require steroids, and have no evidence of progression for at least 8 weeks following treatment of known brain metastases, are eligible.
- Baseline diastolic blood pressure > 95 mmHg. Blood pressure medications may be used to bring the diastolic pressure to levels acceptable for protocol enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular cardiac arrhythmia, myocardial infarction within the previous 6 months, dyspnea at rest, active GI bleeding or ulcer disease, diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because everolimus and imatinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with everolimus and imatinib, breastfeeding should be discontinued if the mother is treated on this protocol. These potential risks may also apply to other agents used in this study.
- Known HIV-positive patients, because of the potential for pharmacokinetic interactions with everolimus and imatinib, and because the potential immunosuppressive actions of everolimus may increase progression or infectious complications of HIV. Appropriate studies will be undertaken in HIV-positive patients when indicated.
- Patients receiving warfarin (see section 5.2), or chronic treatment with steroids or another immunosuppressive agent. In addition, patients requiring the following agents are excluded from the study, and must not take the agents while on the trial: ketoconazole, itraconazole, erythromycin, clarithromycin, dexamethasone, phenytoin, carbamazepine, rifampin, Phenobarbital, St. John's Wort, simvastatin, other HMG-CoA reductase inhibitors (if metabolized by CYP3A4), cyclosporine, pimozide, triazolo-benzodiazepines, dihydropyridine calcium channel blockers, and acetaminophen or acetaminophen containing products such as Percoset or Vicodin. Patients taking CYP3A4 interacting agents with narrow therapeutic windows will be excluded from the trial.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not a allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Comprehensive Cancer Center at Yale University School of Medicine
New Haven, Connecticut, 06520-8028
About this study
Official title: A Phase II Study of Everolimus in Combination With Imatinib in Metastatic Melanoma
The purpose of this study is to determine if the combination of everolimus and imatinib will slow the growth of or cause a reduction in the size of the cancer, and to determine the side effects of the combination in patients with melanoma. Each of the drugs in this combination, if used alone, would not be expected to have an effect against the cancer. However, when used together, there is a possibility that they could work together to damage the cancer cells, or to block the formation or function of the blood vessels that feed the cancer, either of which could result in slowing the growth of or shrinking the cancer. Both drugs work by blocking signals that are sent from outside of a cell to the inside of the cell that direct the cell to make certain substances to keep the cell alive. Cancer cells or blood vessels that feed cancer cells may be more sensitive to drugs that block these signals.
- Conditions
- Metastatic Melanoma
- Being tested
- everolimus, Imatinib
- Keywords
- everolimus, imatinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
ImatinibDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate (as defined by RECIST)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2006 (estimated)
- Study startFeb 2006
- Primary completionJun 2006
- Study completionJun 2006
Why it stopped: unexpected level of toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Yale 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Mario Sznol, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00402662
- Sponsor's protocol ID
- 0508000541
- Status last verified
- Dec 2013
- First submitted
- 20 Nov 2006
- Last updated
- 18 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Everolimus in Combination With Imatinib in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00402662
- Acronym / sponsor ID
- 0508000541
- Conditions
- Metastatic Melanoma
- Keywords
- everolimus, imatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: unexpected level of toxicity
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Feb 2006
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jun 2006 (actual)
- First posted
- 22 Nov 2006 (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.
The purpose of this study is to determine if the combination of everolimus and imatinib will slow the growth of or cause a reduction in the size of the cancer, and to determine the side effects of the combination in patients with melanoma. Each of the drugs in this combination, if used alone, would not be expected to have an effect against the cancer. However, when used together, there is a possibility that they could work together to damage the cancer cells, or to block the formation or function of the blood vessels that feed the cancer, either of which could result in slowing the growth of or shrinking the cancer. Both drugs work by blocking signals that are sent from outside of a cell to the inside of the cell that direct the cell to make certain substances to keep the cell alive. Cancer cells or blood vessels that feed cancer cells may be more sensitive to drugs that block these signals.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have histologically confirmed stage III unresectable or stage IV metastatic melanoma. Patients must have measurable disease as defined by RECIST criteria.
- Patients with up to 1 prior cytotoxic regimen for metastatic disease will be eligible. There will be no prior limitation on adjuvant therapies for stage II/III disease or for patients with stage IV disease treated after resection of all metastatic disease. There will be no prior limitation on biological or hormonal therapies (immune therapies, interferon, hypomethylating agents, histone deacetylase inhibitors, etc.), however, patients previously treated with mTOR inhibitors will be excluded. Prior treatment for metastatic disease is not required. Patients must have recovered from the acute toxicities of prior treatment. Chronic toxicities must have recovered to ≤ grade 1. The minimum interval between prior treatment and first day of dosing on this trial is as follows: standard cytotoxic agents and radiation therapy, 21 days; mitomycin and nitrosoureas, 6 weeks; hormonal and immunotherapy agents, 2 weeks; minor surgery, 2 weeks, major surgery, 3 weeks; investigational agents 4-weeks.
- Age >18 years. Because no dosing or adverse event data are currently available on the use of everolimus in combination with imatinib in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
- ECOG performance status < 1.
- Life expectancy of greater than 3 months.
Key exclusion criteria (8 listed)
- Patients may not be receiving any other investigational agents. Patients may not have received prior treatment for their cancer with an mTOR inhibitor.
- Patients with known brain metastases or leptomeningeal disease are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with previously treated brain metastases, who no longer require steroids, and have no evidence of progression for at least 8 weeks following treatment of known brain metastases, are eligible.
- Baseline diastolic blood pressure > 95 mmHg. Blood pressure medications may be used to bring the diastolic pressure to levels acceptable for protocol enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular cardiac arrhythmia, myocardial infarction within the previous 6 months, dyspnea at rest, active GI bleeding or ulcer disease, diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because everolimus and imatinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with everolimus and imatinib, breastfeeding should be discontinued if the mother is treated on this protocol. These potential risks may also apply to other agents used in this study.
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 |
|---|---|---|
| everolimus | Drug | – |
| Imatinib | Drug | – |
Primary outcome
Response rate (as defined by RECIST)
Results and safety
The study was stopped early (reason given: unexpected level of toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
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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.
Mario Sznol, M.D. principal investigator
Yale University
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 and Imatinib in people with Metastatic Melanoma, run by Yale University 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 9 inclusion and 8 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 18 Dec 2013. 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?
The study was stopped early (reason given: unexpected level of toxicity). 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?
Response rate (as defined by RECIST). 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 18 Dec 2013.