Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib

NCT01519427 | Terminated Phase 2 Results DMC

• 6 other identifiers: NCI-2012-00238CDR0000722048VICCMEL11208867N01CM0010016950
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well selumetinib and Akt inhibitor MK2206 works in treating patients with stage III or stage IV melanoma who failed prior therapy with vemurafenib or dabrafenib. Selumetinib and Akt inhibitor MK2206 stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet know whether giving selumetinib and Akt inhibitor MK2206 together is an effective treatment for advanced melanoma.

Conditions

Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response

  Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

  On-treatment date to date of progressive disease (assessed up to 30 days after end of treatment)

Secondary Outcomes (3)

• Changes in Biomarker Expression

  Before initiation of treatment and at 7-14 days, up to 2 years

• Progression-free Survival (PFS)

  On-study to lesser of date of progression or date of death from any cause, up to 2 years

• Overall Survival

  On-study date to date of death from any cause, up to 2 years

Study Arms (1)

Treatment (selumetinib and Akt inhibitor MK2206)

EXPERIMENTAL

Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.

Drug: Akt inhibitor MK2206; Drug: selumetinib; Other: laboratory biomarker analysis

Interventions

Akt inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (selumetinib and Akt inhibitor MK2206)

selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244

Treatment (selumetinib and Akt inhibitor MK2206)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (selumetinib and Akt inhibitor MK2206)

Eligibility Criteria

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

You may qualify if:

• Patients must have incurable unresectable stage III or IV histologically confirmed Melanoma with V600-mutant BRAF disease and must have progressed after therapy on selective BRAF inhibitor; all patients must have biopsiable tumor and a biopsy must be performed with the collection of FFPE and if possible FF prior to initiation of treatment on this protocol; archival tumor tissue must also be obtained if at all available; this required biopsy will not be necessary if a previous biopsy of progressing tumor after selective BRAF therapy had already been obtained and is adequate
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral computed tomography (CT) scan
• Patients must have received prior therapy and progressed following a selective BRAF inhibitor (i.e., vemurafenib, dabrafenib, LGX818, etc.); patients must have completed prior therapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation therapy; all treatment related toxicity must have resolved to grade 2 or less as well; patients may initiate the protocol treatment at 48 hours following the completion of BRAF inhibitor; patients must have had no more than 2 prior chemotherapy regimens; patients cannot receive chemotherapy after the BRAF inhibitor treatment and prior to enrollment on this protocol; up to two prior immunotherapy regimens for advanced disease are allowed and one may be given between BRAF inhibitor therapy and this trial
• Patients must not be refractory to the BRAF inhibitor; patients must demonstrate some degree of tumor regression initially on BRAF inhibitor prior to progression; (tumor regression does not require RECIST objective response); they cannot have progressive disease at the time of first evaluation (4 or 8 weeks) on the BRAF inhibitor
• Baseline Ophthalmologic exam must be done at screening to include slit lamp exam and fundoscopy; an OCT scan should be considered in case of retinal abnormality at exam
• Life expectancy of greater than or equal to 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥ 70%)
• Absolute neutrophil count ≥ 1,500 mm³
• Hemoglobin ≥ 9.0 g/dL (patients may be transfused to achieve level)
• Platelet count ≥ 100,000/μL
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase(SGPT) \< 2.5 X upper limit of normal (ULN)
• Total bilirubin \< 1.5 mg/dL
• Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance \> 50 mL/min, determined by 24-hour urine collection
• Fasting blood glucose \< 160 mg/dL OR
• HgbA1C \< 8% disease (uncontrolled diabetes)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Emory University

Atlanta, Georgia, 30322, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

MK 2206; 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

Limitations and Caveats

Because this study terminated early due to slow accrual, data were available for only the two eligible patients that enrolled before study closure.

Results Point of Contact

• Title: Jeff Sosman, MD
• Organization: Vanderbilt-Ingram Cancer Center

jeff.sosman@vanderbilt.edu

615-936-3048

Study Officials

• Jeffrey Sosman

  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: January 25, 2012
• First Posted: January 27, 2012
• Study Start: January 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 18, 2014
• Results First Posted: June 18, 2014

Record last verified: 2014-01

Locations

US (4)