TerminatedNCT01166126Updated May 15, 2014Results posted

Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV

A Phase 2 interventional study of temsirolimus and selumetinib in Mucosal Melanoma, Recurrent Melanoma and Stage IV Melanoma, sponsored by National Cancer Institute (NCI). Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-15.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 4
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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. 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:

I. 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:

I. 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 studied

Mucosal Melanoma
Recurrent Melanoma
Stage IV Melanoma

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Melanoma 3,005

In context

Melanoma

3,005 studies on the registry are indexed under Melanoma; 519 are open to participants now.

This study's enrollment of 4 is below the median of 38 across 2,350 interventional studies indexed under Melanoma.

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Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
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

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 4 participants (actual)

Study arms

Experimental
Treatment (temsirolimus and selumetinib)
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.
Drug: temsirolimus · Drug: selumetinib · Other: laboratory biomarker analysis

Interventions

Drugtemsirolimus
Given IV
Also known as: CCI-779, cell cycle inhibitor 779, Torisel
Drugselumetinib
Given orally
Also known as: ARRY-142886, AZD6244
Otherlaboratory biomarker analysis
Correlative studies

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 1 year post last treatment

Secondary outcomes

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).
Time frame: 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.
Time frame: 1 year

Results

Posted May 23, 2013

Limitations and caveats

The study was terminated due to overall low accrual and a high rate of screening failures. Accrual goal was 38 participants and only 4 participants were actually treated.

Participant flow

Up to 35 subjects with a histologic diagnosis of unresectable Stage IV melanoma were to be enrolled into this study over 24 months.

Participant flow — Overall Study
Milestone	Treatment (Temsirolimus and Selumetinib)
Started	4
Completed	4
Not completed	0

Outcome measures

PrimaryNumber 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.

Time frame:: 1 year
Reported as:: Number · participants

Number of Participants With Complete Response (CR) and Partial Response (PR)
participants	Treatment (Temsirolimus and Selumetinib)
Complete Response	0
Partial Response	0

PrimaryNumber of Participants With Overall Survival (OS) at One Year

The one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.

Time frame:: 1 year post last treatment
Reported as:: Number · participants

Number of Participants With Overall Survival (OS) at One Year
participants	Treatment (Temsirolimus and Selumetinib)
Number of Participants With Overall Survival (OS) at One Year	0

SecondaryNumber 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).

Time frame:: 6 months from day 1 of treatment
Reported as:: Number · participants

Number of Participants With Progression Free Survival (PFS) at 6 Months.
participants	Treatment (Temsirolimus and Selumetinib)
Number of Participants With Progression Free Survival (PFS) at 6 Months.	1

SecondaryNumber of Participants With Related Serious Adverse Events (SAEs)

Toxicities assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.

Time frame:: 1 year
Reported as:: Number · participants

Number of Participants With Related Serious Adverse Events (SAEs)
participants	Treatment (Temsirolimus and Selumetinib)
Number of Participants With Related Serious Adverse Events (SAEs)	0

Adverse events

Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Treatment (Temsirolimus and Selumetinib)	—	2/4 (50%)	4/4 (100%)

Most frequent serious events

Most frequent serious events
Event	Treatment (Temsirolimus and Selumetinib)
VertigoEar and labyrinth disorders	1/4
DiarrheaGastrointestinal disorders	1/4
NauseaGastrointestinal disorders	1/4
FeverGeneral disorders	1/4
DehydrationMetabolism and nutrition disorders	1/4
Neoplasms benigh, malignant and unspecified (incl cysts and polyps) - otherNeoplasms benign, malignant and unspecified (incl cysts and polyps)	1/4

Most frequent other events

Showing 10 of 52

Most frequent other events
Event	Treatment (Temsirolimus and Selumetinib)
ConstipationGastrointestinal disorders	4/4
Mucositis oralGastrointestinal disorders	4/4
FatigueGeneral disorders	4/4
NauseaGastrointestinal disorders	3/4
FeverGeneral disorders	3/4
Pain of skinSkin and subcutaneous tissue disorders	3/4
Rash maculo-papularSkin and subcutaneous tissue disorders	3/4
CoughRespiratory, thoracic and mediastinal disorders	3/4
DiarrheaGastrointestinal disorders	2/4
Edima - limbsGeneral disorders	2/4

Baseline characteristics

All baseline participants

Age, Categorical
Age, Categorical(Participants)	Treatment (Temsirolimus and Selumetinib)
<=18 years	0
Between 18 and 65 years	3
>=65 years	1

Age, Continuous
Age, Continuous(years)	Treatment (Temsirolimus and Selumetinib)
Mean	52.5 (39 to 69)

Sex: Female, Male
Sex: Female, Male(Participants)	Treatment (Temsirolimus and Selumetinib)
Female	1
Male	3

Region of Enrollment
Region of Enrollment(participants)	Treatment (Temsirolimus and Selumetinib)
United States	4

Study locations

1 site

H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 15, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01166126
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jul 20, 2010
Start date: Oct 2010
Primary completion: Jun 2012
Completion: Jun 2012
Results posted: May 23, 2013
Last update: May 15, 2014

Study contacts

Ragini Kudchadkar

principal investigator · H. Lee Moffitt Cancer Center and Research Institute

View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Dec 2012. You cannot join it, but the record below documents what was studied.

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