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

NCT01166126 | Terminated Phase 2 Results

• 4 other identifiers: NCI-2012-02846MCC-160668436P30CA076292
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Mucosal Melanoma; Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  1 year post last treatment

Secondary Outcomes (2)

• Number of Participants With Progression Free Survival (PFS) at 6 Months.

  6 months from day 1 of treatment

• Number of Participants With Related Serious Adverse Events (SAEs)

  1 year

Study Arms (1)

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.

Drug: temsirolimus; Drug: selumetinib; Other: laboratory biomarker analysis

Interventions

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, Torisel

Treatment (temsirolimus and selumetinib)

selumetinib DRUG

Given orally

Also known as: ARRY-142886, AZD6244

Treatment (temsirolimus and selumetinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (temsirolimus and selumetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

temsirolimus; Sirolimus; AZD 6244

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

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.

Results Point of Contact

• Title: Ragini Kudchadkar, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

ragini.kudchadkar@moffitt.org

813-745-8581

Study Officials

• Ragini Kudchadkar

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 20, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: May 15, 2014
• Results First Posted: May 23, 2013

Record last verified: 2012-12

Locations

US (1)