Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT02094872
First received: March 18, 2014
Last updated: August 18, 2015
Last verified: August 2015
  Purpose

This randomized phase II trial studies how well molecularly targeted therapy works in treating patients with melanoma that has spread to other parts of the body. Patients must have received or do not qualify for prior immunotherapy. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Molecularly targeted therapy works by treating patients with substances that kill cancer cells by targeting key molecules involved in cancer cell growth.


Condition Intervention Phase
Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Other: cytology specimen collection procedure
Drug: molecularly targeted therapy
Procedure: therapeutic procedure
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Stand Up to Cancer Consortium Genomics-Enabled Medicine for Melanoma (G.E.M.M.): Using Molecularly-Guided Therapy for Patients With BRAF Wild-Type (BRAFwt) Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • BORR [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ] [ Designated as safety issue: No ]
    A log rank test will be performed for the comparison between the two groups.


Estimated Enrollment: 96
Study Start Date: May 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (molecularly targeted therapy)
Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: cytology specimen collection procedure
Undergo collection of tissue and blood samples
Other Name: cytologic sampling
Drug: molecularly targeted therapy
molecularly targeted therapy
Other Names:
  • Doxorubicin
  • Rubex ®
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Arm II (standard of care therapy)
Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Patients receive physician's choice standard of care therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: cytology specimen collection procedure
Undergo collection of tissue and blood samples
Other Name: cytologic sampling
Procedure: therapeutic procedure
Receive standard of care therapy
Other Names:
  • Therapeutic Interventions
  • Therapeutic Method
  • Therapeutic Technique
  • Therapy
  • TX
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the difference in best overall response rate (BORR) between patients treated with personalized targeted treatment vs. those treated with physician's choice of standard therapy.

SECONDARY OBJECTIVES:

I. To evaluate the safety of performing individualized drug therapy (including novel agents and commercially-available agents) in the context of a personalized medicine clinical trial.

II. To continually assess the process of enrolling and treating patients to a personalized medicine clinical trial by acquiring blood and tissue, genetically characterizing v-raf murine sarcoma viral oncogene homolog B (BRAF) wild type (wt) metastatic melanoma tumors, identifying a list of potential driver mutations, and treating each patient within a 5-week time frame.

III. To determine the difference in progression free survival (PFS) between patients treated with personalized targeted treatment vs. those treated with physician's choice therapy.

IV. To determine the BORR in specific target-drug matchings (those more frequent).

V. To iteratively refine and standardize a set of statistical and informatics methodologies for matching treatments to the patient's tumor, based on their molecular profile.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo collection of tissue and blood samples for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Patients receive physician's choice standard of care therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with metastatic or locally advanced and unresectable BRAF wild-type melanoma who have either progressed following previous treatment of immunotherapy, or are not eligible for immunotherapy; pts. are defined as "BRAF wild-type" if they test negative for V600 mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay
  • Patients must have tumor accessible by interventional radiology or surgical intervention and suitable for biopsy (BX) with 5-6 passes of a 16 or 18 gauge needle for core BX (defined as at least 1 cm^3 tumor/50 mg accessible for BX), and must agree to undergo up to two surgical resections/biopsies to collect tumor for research purposes; the first of these biopsies will occur at the beginning of the study, prior to genetic analysis and Rx; the second BX will be performed at the time of DZ progression/end of study should funding be available
  • Patients must have measurable DZ (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 [v1.1] criteria), 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, magnetic resonance imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam; for lymph nodes, the short axis must be >= 15 mm
  • Previous therapies: prior radiation therapies, immunotherapies, and investigational therapies are allowed as follows.

    • Radiation: prior radiation therapy (RT) is allowed with the following conditions:

      • Patients who have received minimal RT (=< 5% of their total marrow volume) must have completed it >= 2 weeks prior to the initiation of study Rx
      • Patients who have received RT that constituted > 5% but < 50% of their total marrow volume must have completed it >= 4 weeks prior to the initiation of study treatment
      • Patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
      • Patients may be biopsied while undergoing RT as long as BX site is not in the radiation portal; however, they still have to wait the required amount of time from radiation to treatment even though the tumor board may have already occurred and a treatment plan assigned
    • Other therapies: prior investigational or targeted therapies and immunotherapies may be allowed following discussion with the PI (PI); if the PI deems the prior treatment acceptable, patients must not have received these therapies for 28 days or five half-lives of the drug (whichever is lesser) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies; prior therapy with mitogen-activated protein kinase (MEK) inhibitors will not be allowed
  • Patients with chronic grade 1 or 2 toxicity may be eligible at the discretion of the PI if the condition has been stable, and not worsening, for at least 30 days; pts. with ongoing alopecia of any grade will be eligible
  • Patient must have a life expectancy of >= 3 months, as estimated by the treating oncologist
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin >= 9 g/dL
  • Leukocytes >= 3,000/microliter (mcL)
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets (PLT) >= 100,000/mcL
  • Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN); if liver metastases are present, =< 5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN; if liver metastases are present, =< 5 x ULN
  • Bilirubin =< 1.5 x ULN
  • Creatinine =< 1.5 x ULN OR calculated or measured creatinine clearance >= 50 mL/min/1.73 m^2 for pts. with creatinine above institutional normal
  • If available, pt. must agree to provide archival tissue for research purposes (either archival paraffin tissue block or 10 unstained slides of a primary or metastatic melanoma lesion) prior to enrollment; samples should be shipped within 1 month after enrollment
  • Patient agrees to having a blood sample (a minimum of 10 mL, with 20 mL preferred) drawn and analyzed to compare their normal genetic profile to that of their tumor sample
  • Patient must be able to tolerate oral medication
  • Women of child-bearing potential and men must agree to use 2 forms of adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women who become pregnant must immediately discontinue Rx with any study therapy; male pts. should avoid impregnating a female partner; male pts., even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study Rx period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse
  • Patient must have the ability to understand and the willingness to sign a written informed consent document
  • Patient must be willing and able to comply with the protocol for the duration of the study, including attending scheduled visits, examinations, the BX procedure, and having their tumor and blood molecularly characterized
  • Patient understands if he or she is randomized to receive molecularly guided treatment, they must meet all inclusion and exclusion criteria in the drug specific appendix for which they were randomized

Exclusion Criteria:

  • Patients with peripheral neuropathy >= grade 2 are not permitted unless discussed with the PI and only in unique circumstances (i.e. unilateral neuropathy due to trauma)
  • Patient has DZ that tests positive for BRAF V600 mutations based on the results of a CLIA certified assay
  • Patients with active infection at time of BX
  • Patients with any evidence of severe or uncontrolled systemic DZ(s) including known cases of hepatitis B or C or human immunodeficiency virus (HIV); screening for chronic conditions is not required, although pts. known to have such conditions at screening should not be included
  • Any patient requiring chronic maintenance of red blood cell, white blood cell or granulocyte counts through the use of blood transfusions or growth factor support (e.g. Neulasta®, Neupogen®)
  • Patients with a prior history of seizures within the past year unrelated to brain metastases
  • Patients with known active progressive brain metastases; pts. with prior treated brain metastases are allowed, providing that they were not accompanied by seizures within the past year and that a baseline brain MRI scan prior to study entry demonstrates no current evidence of active brain metastases; all pts. with prior treated brain metastases must be stable for > 1 months after treatment and off steroid treatment prior to study enrollment
  • Patients receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started >= month prior to enrollment on this study; pts. may be on low molecular weight heparin or direct factor Xa inhibitors
  • Patients with any clinically significant medical condition which, in the opinion of the investigator, makes it undesirable for the pt. to participate in the study or which could jeopardize compliance with protocol requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations
  • Patients with preexisting cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure will not be eligible
  • Patients with left ventricular ejection fraction (LVEF) < 45% will not be eligible
  • Patients with either of the following within 6 months before the first dose of study treatment:

    • Stroke (including transient ischemic attack [TIA], or other ischemic event)
    • Myocardial infarction
  • Patients with acute gastrointestinal bleeding within 1 month of study entry
  • Patients who have, at screening, corrected QT interval using Fridericia's formula (QTcF) >= 450 msec for males and QTcF >= 470 for females
  • Patients with a co-morbid condition(s) that, in the opinion of the investigator, prevents safe surgery/BX procedure
  • Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption or ability to swallow oral medication
  • Pregnant or nursing women; breastfeeding must be discontinued prior to Rx
  • Patients who have received organ transplant
  • Patients who have had major surgery within 14 days of study enrollment
  • Patients diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, or an in situ malignancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02094872

Contacts
Contact: Lisa Fox 203-737-7139 Lisa.Fox@yale.edu
Contact: Julie Holub 203-737-4784 julie.holub@yale.edu

Locations
United States, Arizona
Mayo Clinic Cancer Center Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office, Toll Free    855-776-0015      
Principal Investigator: Alan H. Bryce         
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven Recruiting
New Haven, Connecticut, United States, 06520-8028
Contact: Harriet M. Kluger, M.D.    203-737-5172    harriet.kluger@yale.edu   
Principal Investigator: Harriet M. Kluger, M.D.         
United States, Florida
Mayo Clinic Cancer Center Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office, Toll Free    855-776-0015      
Principal Investigator: Richard W. Joseph         
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Jon Thomas Diener    317-278-6401    jtdiener@iupui.edu   
Principal Investigator: Ted Logan         
United States, Maryland
National Cancer Institute Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: Shivaani Kummar, M.D.    301-435-5402    kummars@exchange.nih.gov   
Principal Investigator: Shivaani Kummar, M.D.         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109-0944
Contact: Patty Harvey       harveypj@med.umich.edu   
Principal Investigator: Leslie Fecher, MD         
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Clarice Zuccaro, BA, CCRP    313-576-9375    zuccaroc@karmanos.org   
Sub-Investigator: Lawrence Flaherty, M.D.         
Sub-Investigator: Louis Penner, Ph.D.         
Sub-Investigator: Ulka N. Vaishampayan, M.D.         
Principal Investigator: Amy Weise, D.O.         
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office, Toll Free    855-776-0015      
Principal Investigator: Svetomir N. Markovic         
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: K.         
Principal Investigator: Gary K. Schwartz         
Memorial Sloan-Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Paul B. Chapman    646-888-2378    chapmanp@mskcc.org   
Principal Investigator: Paul B. Chapman, M.D.         
Sub-Investigator: Jedd D. Wolchok, M.D., PhD         
United States, Pennsylvania
UPMC Cancer Center - Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15241
Contact: Hussein A. Tawbi    412-648-6466    tawbih@upmc.edu   
Principal Investigator: Hussein A. Tawbi         
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37240
Contact: Jonathan Gephart         
Principal Investigator: Douglas Johnson, MD         
United States, Texas
Baylor Sammons Cancer Center Not yet recruiting
Dallas, Texas, United States, 75246
Contact: Charles L. Cowey    214-370-1800      
Principal Investigator: Charles L. Cowey         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Patricia LoRusso, D.O. Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02094872     History of Changes
Other Study ID Numbers: HIC # 1408014446, NCI-2014-00670, WIRB Pro #20140190, WO #1-822810-1, Invest #161467, Study #1144561, 2013-184, P30CA022453
Study First Received: March 18, 2014
Last Updated: August 18, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 31, 2015