Mucosal MelanomaPhase 2NCT01166126
Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV
A Phase 2 study testing temsirolimus, selumetinib and laboratory biomarker analysis in people with Mucosal Melanoma and Recurrent Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
The purpose of this study is to find out how often two investigational drugs that are given together will shrink the patient's tumor and how well they will prolong the time it takes their tumor to grow. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucosal Melanoma, Recurrent Melanoma, Stage IV Melanoma
- What is being tested?
- temsirolimus, selumetinib and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Jun 2012
- 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
- Subject must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained
- Subjects with a histologic diagnosis of unresectable stage IV melanoma (may include mucosal melanoma)
- Tumor must be BRAF V600E mutation positive from a certified lab
- At least 4 weeks since any previous treatment (surgery, radiotherapy, or systemic treatment)
- Women should be either: post-menopausal for at least 1 year; surgically incapable of bearing children; or utilizing a reliable form of contraception during the study and for at least 4 months after the final study drug infusion or ingestion; women of childbearing potential must have a negative serum hCG-beta pregnancy test conducted during the screening period
- Men who may father a child must agree to the use of male contraception for the duration of their participation in the trial and for at least 4 months after the final temsirolimus and AZD6244 hydrogen sulfate administration
Show all 21Show fewer
- Life expectancy >= 3 months
- ECOG performance status of 0 or 1
- Patients with brain metastases treated with surgery, radiation, or stereotactic radiosurgery who are without evidence of progression in their brain metastases after MRI imaging performed at least 30 days after treatment, and are not taking systemic steroids will be eligible
- WBC >= 3000 cells/mm^3
- ANC >= 1500 cells/mm^3
- Platelets >= 100,000/mm^3
- Hematocrit >= 30%
- Hemoglobin >= 9 g/dL
- Creatinine =< 2.0 mg/dL
- AST/ALT =< 2 x ULN
- Bilirubin =< 1.5 x ULN, (except subjects with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL)
- HIV negative
- HBsAg negative
- Anti-HCV Ab nonreactive; if reactive, subject must have a negative HCV RNA qualitative PCR
- Patients with hyperlipidemia must have adequate control with a lipid lowering agent
Who cannot join
- Any prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer from which the subject has been disease-free for at least 5 years
- Active infection, requiring therapy, chronic active HBV or HCV; patients with HIV, who have adequate CD4 counts and who do not require HAART therapy, are NOT excluded
- Pregnancy or nursing: due to the possibility that temsirolimus and AZD6244 hydrogen sulfate could have a detrimental effect on the developing fetus or infant, exposure in utero or via breast milk will not be allowed
- Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events
- Prior treatment with temsirolimus or AZD6244 or any prior mTOR or MEK inhibitor
- Evidence or history of significant cardiac, pulmonary, hepatic, renal, psychiatric or gastrointestinal disease that would make the administration of temsirolimus or AZD6244 hydrogen sulfate unsafe
- Tumor that is BRAF V600E mutation negative
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase II Trial of mTOR Inhibitor Temsirolimus Combined With MEK Inhibitor AZD 6244 in Patients With BRAF Mutant Stage IV Melanoma
The purpose of this study is to find out how often two investigational drugs that are given together will shrink the patient's tumor and how well they will prolong the time it takes their tumor to grow. The investigators also wish to find out how they affect certain substances in the patient's tumor and in their blood important for tumor growth. The combination of these drugs is experimental, and has not been proven to help treat melanoma
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the clinical response rate (Response Evaluation Criteria in Solid Tumors [RECIST]) and one-year overall survival to the study drugs temsirolimus and AZD6244 (selumetinib) hydrogen sulfate in BRAF V600E mutant unresectable stage IV melanoma.
SECONDARY OBJECTIVES:
- Estimate 6-month progression-free survival in patients receiving temsirolimus and AZD6244 hydrogen sulfate.
II. Determine the pharmacodynamic effects of temsirolimus and AZD6244 on pERK, s6K, PTEN and mediators of apoptosis.
III. Determine the toxicity profile of temsirolimus with AZD6244 hydrogen sulfate.
OUTLINE:
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
As many as 38 patients will receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 will be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 will be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 will be given every 8 weeks. The TEMSIROLIMUS will be injected in a vein over 30 minutes.
The continuation phase begins with visits at weeks 12 in patients who receive at least two cycles of treatments.
- Conditions
- Mucosal Melanoma, Recurrent Melanoma, Stage IV Melanoma
- Being tested
- temsirolimus, selumetinib, laboratory biomarker analysis
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temsirolimusDrug
Also called CCI-779, cell cycle inhibitor 779, Torisel
Given IV
selumetinibDrug
Also called ARRY-142886, AZD6244
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temsirolimus and selumetinib) | Experimental | Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
As many as 38 patients will receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 will be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 will be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 will be given every 8 weeks. The TEMSIROLIMUS will be injected in a vein over 30 minutes.
The continuation phase begins with visits at weeks 12 in patients who receive at least two cycles of treatments. Receives: Drug: temsirolimus; Drug: selumetinib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response (CR) and Partial Response (PR)
Anti-tumor response (CR+PR) was defined by Response Evaluation Criteria in Solid Tumors (RECIST).
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 1 year
Number of Participants With Overall Survival (OS) at One Year
The one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.
Measured: 1 year post last treatment
Secondary outcomes (2)
Number of Participants With Progression Free Survival (PFS) at 6 Months.
Patients will be evaluated by physical examination and imaging assessments (brain MRI and CT scans of the chest, abdomen and pelvis). Disease progression will be defined by RECIST criteria on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma.
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: 6 months from day 1 of treatment
Number of Participants With Related Serious Adverse Events (SAEs)
Toxicities assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2012
- Study completionJun 2012
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 Mucosal MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ragini Kudchadkar, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01166126
- Sponsor's protocol ID
- NCI-2012-02846
- Other IDs
- NCI-2012-02846, MCC-16066, 8436, P30CA076292
- Status last verified
- Dec 2012
- First submitted
- 12 Jul 2010
- Last updated
- 15 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of mTOR Inhibitor Temsirolimus Combined With MEK Inhibitor AZD 6244 in Patients With BRAF Mutant Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT01166126
- Acronym / sponsor ID
- NCI-2012-02846
- Conditions
- Mucosal Melanoma, Recurrent Melanoma, Stage IV Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 20 Jul 2010 (estimated)
- Results
- Posted 23 May 2013
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 find out how often two investigational drugs that are given together will shrink the patient's tumor and how well they will prolong the time it takes their tumor to grow. The investigators also wish to find out how they affect certain substances in the patient's tumor and in their blood important for tumor growth. The combination of these drugs is experimental, and has not been proven to help treat melanoma
Detailed description
PRIMARY OBJECTIVES:
- To determine the clinical response rate (Response Evaluation Criteria in Solid Tumors [RECIST]) and one-year overall survival to the study drugs temsirolimus and AZD6244 (selumetinib) hydrogen sulfate in BRAF V600E mutant unresectable stage IV melanoma.
SECONDARY OBJECTIVES:
- Estimate 6-month progression-free survival in patients receiving temsirolimus and AZD6244 hydrogen sulfate.
II. Determine the pharmacodynamic effects of temsirolimus and AZD6244 on pERK, s6K, PTEN and mediators of apoptosis.
III. Determine the toxicity profile of temsirolimus with AZD6244 hydrogen sulfate.
OUTLINE:
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
As many as 38 patients will receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 will be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 will be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 will be given every 8 weeks. The TEMSIROLIMUS will be injected in a vein over 30 minutes.
The continuation phase begins with visits at weeks 12 in patients who receive at least two cycles of treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temsirolimus and selumetinib) | Experimental | Drug: temsirolimus, Drug: selumetinib, Other: laboratory biomarker analysisTreatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4). As many as 38 patients will receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 will be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 will be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 will be given every 8 weeks. The TEMSIROLIMUS will be injected in a vein over 30 minutes. The continuation phase begins with visits at weeks 12 in patients who receive at least two cycles of treatments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Subject must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained
- Subjects with a histologic diagnosis of unresectable stage IV melanoma (may include mucosal melanoma)
- Tumor must be BRAF V600E mutation positive from a certified lab
- At least 4 weeks since any previous treatment (surgery, radiotherapy, or systemic treatment)
- Women should be either: post-menopausal for at least 1 year; surgically incapable of bearing children; or utilizing a reliable form of contraception during the study and for at least 4 months after the final study drug infusion or ingestion; women of childbearing potential must have a negative serum hCG-beta pregnancy test conducted during the screening period
Key exclusion criteria (7 listed)
- Any prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer from which the subject has been disease-free for at least 5 years
- Active infection, requiring therapy, chronic active HBV or HCV; patients with HIV, who have adequate CD4 counts and who do not require HAART therapy, are NOT excluded
- Pregnancy or nursing: due to the possibility that temsirolimus and AZD6244 hydrogen sulfate could have a detrimental effect on the developing fetus or infant, exposure in utero or via breast milk will not be allowed
- Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events
- Prior treatment with temsirolimus or AZD6244 or any prior mTOR or MEK inhibitor
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 |
|---|---|---|
| temsirolimusAlso: CCI-779, cell cycle inhibitor 779, ToriselGiven IV | Drug | Treatment (temsirolimus and selumetinib) |
| selumetinibAlso: ARRY-142886, AZD6244Given orally | Drug | Treatment (temsirolimus and selumetinib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (temsirolimus and selumetinib) |
Primary outcome
Number of Participants With Complete Response (CR) and Partial Response (PR)
Time frame: 1 year
Anti-tumor response (CR+PR) was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Overall Survival (OS) at One Year
Time frame: 1 year post last treatment
The one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.
2 secondary outcomes
Number of Participants With Progression Free Survival (PFS) at 6 Months.
Time frame: 6 months from day 1 of treatment
Number of Participants With Related Serious Adverse Events (SAEs)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ragini Kudchadkar principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 temsirolimus, selumetinib and laboratory biomarker analysis in people with Mucosal Melanoma and Recurrent Melanoma, run by National Cancer Institute (NCI) 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 21 inclusion and 7 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 15 May 2014. 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 23 May 2013). 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?
Number of Participants With Complete Response (CR) and Partial Response (PR) (time frame: 1 year). The study lists 2 primary outcomes in all. 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 15 May 2014.