Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01166126
Recruitment Status : Terminated
First Posted : July 20, 2010
Results First Posted : May 23, 2013
Last Update Posted : May 15, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Mucosal Melanoma
Recurrent Melanoma
Stage IV Melanoma
Interventions Drug: temsirolimus
Drug: selumetinib
Other: laboratory biomarker analysis
Enrollment 4
Recruitment Details Up to 35 subjects with a histologic diagnosis of unresectable Stage IV melanoma were to be enrolled into this study over 24 months.
Pre-assignment Details 11 of 15 patients consented were not eligible to receive the study drug after screening.
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description

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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Period Title: Overall Study
Started 4
Completed 4
Not Completed 0
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description

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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Overall Number of Baseline Participants 4
Hide Baseline Analysis Population Description
All baseline participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
<=18 years
0
   0.0%
Between 18 and 65 years
3
  75.0%
>=65 years
1
  25.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 4 participants
52.5
(39 to 69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Female
1
  25.0%
Male
3
  75.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants
4
1.Primary Outcome
Title Number of Participants With Complete Response (CR) and Partial Response (PR)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description:

Treatment Phase: This period began 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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
Complete Response 0
Partial Response 0
2.Primary Outcome
Title Number of Participants With Overall Survival (OS) at One Year
Hide Description The one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.
Time Frame 1 year post last treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description:

Treatment Phase: This period began 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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title Number of Participants With Progression Free Survival (PFS) at 6 Months.
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description:

Treatment Phase: This period began 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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
1
4.Secondary Outcome
Title Number of Participants With Related Serious Adverse Events (SAEs)
Hide Description Toxicities assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description:

Treatment Phase: This period began 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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
0
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Temsirolimus and Selumetinib)
Hide Arm/Group Description

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).

Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would 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 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.

The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.

All-Cause Mortality
Treatment (Temsirolimus and Selumetinib)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Temsirolimus and Selumetinib)
Affected / at Risk (%) # Events
Total   2/4 (50.00%)    
Ear and labyrinth disorders   
Vertigo  1  1/4 (25.00%)  1
Gastrointestinal disorders   
Diarrhea  1  1/4 (25.00%)  1
Nausea  1  1/4 (25.00%)  1
General disorders   
Fever  1  1/4 (25.00%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/4 (25.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benigh, malignant and unspecified (incl cysts and polyps) - other  1  1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Temsirolimus and Selumetinib)
Affected / at Risk (%) # Events
Total   4/4 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  1/4 (25.00%)  2
Blood and lymphatic system disorders - other  1  1/4 (25.00%)  1
Ear and labyrinth disorders   
Tinnitus  1  1/4 (25.00%)  1
Vertigo  1  1/4 (25.00%)  1
Gastrointestinal disorders   
Constipation  1  4/4 (100.00%)  4
Mucositis oral  1  4/4 (100.00%)  20
Nausea  1  3/4 (75.00%)  8
Diarrhea  1  2/4 (50.00%)  6
Abdominal pain  1  1/4 (25.00%)  1
Ascites  1  1/4 (25.00%)  1
Gastrointestinal disorders - other  1  1/4 (25.00%)  1
Vomiting  1  1/4 (25.00%)  2
General disorders   
Fatigue  1  4/4 (100.00%)  8
Fever  1  3/4 (75.00%)  5
Edima - limbs  1  2/4 (50.00%)  3
Pain  1  2/4 (50.00%)  4
Chills  1  1/4 (25.00%)  1
Edema - face  1  1/4 (25.00%)  1
General disorders and administration site conditions - other  1  1/4 (25.00%)  1
Hepatobiliary disorders   
Hepatic pain  1  1/4 (25.00%)  1
Hepatobiliary disorders - other  1  1/4 (25.00%)  1
Infections and infestations   
Tooth infection  1  1/4 (25.00%)  1
Investigations   
Lipase increased  1  2/4 (50.00%)  2
Alkaline phosphatase increased  1  1/4 (25.00%)  2
Aspartate aminotransferase increased  1  1/4 (25.00%)  1
Cholesterol high  1  1/4 (25.00%)  1
Neutrophil count decreased  1  1/4 (25.00%)  14
Serum amylase increased  1  1/4 (25.00%)  1
Metabolism and nutrition disorders   
Hypertriglyceridemia  1  2/4 (50.00%)  5
Anorexia  1  1/4 (25.00%)  2
Hyperglycemia  1  1/4 (25.00%)  1
Hyponatremia  1  1/4 (25.00%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/4 (25.00%)  2
Pain in extremity  1  1/4 (25.00%)  1
Nervous system disorders   
Dizziness  1  2/4 (50.00%)  2
Dysgeusia  1  1/4 (25.00%)  1
Headache  1  1/4 (25.00%)  2
Paresthesia  1  1/4 (25.00%)  1
Seizure  1  1/4 (25.00%)  1
Psychiatric disorders   
Anxiety  1  2/4 (50.00%)  2
Insomnia  1  2/4 (50.00%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  3/4 (75.00%)  3
Dyspnea  1  2/4 (50.00%)  5
Hiccups  1  1/4 (25.00%)  1
Nasal congestion  1  1/4 (25.00%)  1
Skin and subcutaneous tissue disorders   
Pain of skin  1  3/4 (75.00%)  3
Rash maculo-papular  1  3/4 (75.00%)  9
Pruritus  1  2/4 (50.00%)  4
Rash acneiform  1  2/4 (50.00%)  9
Alopecia  1  1/4 (25.00%)  3
Skin hyperpigmentation  1  1/4 (25.00%)  1
Vascular disorders   
Hypertension  1  1/4 (25.00%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Ragini Kudchadkar, M.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-8581
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01166126     History of Changes
Other Study ID Numbers: NCI-2012-02846
NCI-2012-02846 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MCC-16066 ( Other Identifier: H. Lee Moffitt Cancer Center and Research Institute )
8436 ( Other Identifier: CTEP )
P30CA076292 ( U.S. NIH Grant/Contract )
First Submitted: July 12, 2010
First Posted: July 20, 2010
Results First Submitted: March 29, 2013
Results First Posted: May 23, 2013
Last Update Posted: May 15, 2014