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Phase II Trial of mTOR Inhibitor Temsirolimus Combined With MEK Inhibitor AZD 6244 in Patients With BRAF Mutant Stage IV Melanoma

Phase 2
18 Years
Not Enrolling
Melanoma, Recurrent Melanoma, Stage IV Melanoma

Thank you

Trial Information

Phase II Trial of mTOR Inhibitor Temsirolimus Combined With MEK Inhibitor AZD 6244 in Patients With BRAF Mutant Stage IV Melanoma


I. To determine the clinical response rate according to 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.


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.


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

The continuation phase was to begin with visits at weeks 12 in patients who receive at least
two cycles of treatments.

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

- 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 human chorionic gonadotropin
(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

- Eastern Cooperative Oncology Group (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
magnetic resonance imaging (MRI) performed at least 30 days after treatment, and are
not taking systemic steroids will be eligible

- White blood count (WBC) >= 3000 cells/mm^3

- Absolute neutrophil count (ANC) >= 1500 cells/mm^3

- Platelets >= 100,000/mm^3

- Hematocrit >= 30%

- Hemoglobin >= 9 g/dL

- Creatinine =< 2.0 mg/dL

- Aspartic transaminase (AST)/alanine transaminase (ALT) =< 2 x ULN

- Bilirubin =< 1.5 x upper limit of normal (ULN), (except subjects with Gilbert's
Syndrome who must have a total bilirubin less than 3.0 mg/dL)

- HIV negative

- Hepatitis B surface antigen (HBsAg) negative

- Anti-HCV Ab nonreactive; if reactive, subject must have a negative HCV RNA
qualitative polymerase chain reaction (PCR)

- Patients with hyperlipidemia must have adequate control with a lipid lowering agent

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 hepatitis B virus (HBV) or
hepatitis C virus (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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Complete Response (CR) and Partial Response (PR)

Outcome 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.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Ragini Kudchadkar

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2010

Completion Date:

Related Keywords:

  • Melanoma
  • Recurrent Melanoma
  • Stage IV Melanoma
  • mucosal melanoma
  • Melanoma



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612