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Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Acral Lentiginous Malignant Melanoma, Lentigo Maligna Malignant Melanoma, Nodular Malignant Melanoma, Recurrent Melanoma, Solar Radiation-related Skin Melanoma, Stage IV Melanoma, Superficial Spreading Malignant Melanoma

Thank you

Trial Information

Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma


PRIMARY OBJECTIVES:

I. To assess the six-month progression-free survival and one-year overall survival
probability in Stage IV melanoma patients treated with RO4929097 (gamma-secretase/Notch
signalling pathway inhibitor RO4929097).

SECONDARY OBJECTIVES:

I. To investigate in a preliminary manner the relationship between Notch activation status
and gene expression profile of tumor and clinical outcomes from patients in this study.

II. To study the effects of the investigational therapy on T cell function, which will
provide a basis for subsequent trials combining Notch blockade with immunomodulatory therapy
for advanced melanoma.

III. To assess the response rate (confirmed and unconfirmed complete and partial responses).

IV. To assess toxicity.

OUTLINE: This is a multicenter study.

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) on
days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

Some patients undergo blood collection at baseline and during study for analysis of T-cell
function by flow cytometry and ELISA. Tumor tissue samples from biopsy or surgery are also
analyzed for Notch activation by IHC and qRT-PCR.

After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for 2 years.


Inclusion Criteria:



- Patients must have histologically confirmed melanoma of cutaneous or unknown origin
(ocular primary and mucosal primary excluded); patients must have Stage IV disease

- All patients must undergo a computed tomography (CT) or magnetic resonance imaging
(MRI) of the brain within 42 days prior to registration that is negative for brain
metastases; patients with a history of brain metastases are ineligible

- Patients must have measurable disease; all measurable lesions must be assessed (by
physical examination, CT, or MRI scan) within 28 days prior to registration; tests to
assess non-measurable disease must be performed within 42 days prior to registration;
all disease must be assessed and documented on the Baseline Tumor Assessment Form
(Response Evaluation Criteria In Solid Tumors [RECIST] 1.1); the CT from a combined
positron emission tomography (PET)/CT must not be used to document measurable disease
unless it is of diagnostic quality

- Sites must offer all patients participation in translational medicine studies and
banking of paraffin embedded tissue and whole blood

- Patients must not have received any prior systemic therapy for Stage IV disease
except for noncytotoxic biologic agents (e.g., vaccines, cytokines, cell therapies
that do not require cytotoxic agents); patients may have received prior treatment
with up to two prior biological therapies - no cytotoxics or kinase inhibitors - for
advanced disease

- Patients may have had prior adjuvant immunotherapy with biological response modifiers
(examples include but are not limited to interferon, vaccines, GM-CSF, and CTLA-4
blocking antibodies); prior adjuvant immunotherapy must have been completed at least
28 days prior to registration

- Adjuvant therapy containing cytotoxic agents is allowed if completed >= 180 days
prior to registration

- Patients may have received prior radiation therapy; any side effects the patients had
due to prior radiation therapy must have resolved to =< Grade 1 prior to
registration; prior radiation therapy must have completed at least 28 days prior to
registration

- Patients must have Zubrod performance status of 0-1

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 9 g/dL

- Total bilirubin =< institutional upper limit of normal (IULN)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x IULN

- Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min

- Patients must have the following serum electrolytes within the institutional ranges
of normal: potassium, sodium, magnesium, phosphorous, chloride and calcium (corrected
for serum albumin); these tests must be performed within 28 days prior to
registration; patient must not require parenteral replacement therapy

- Patients must not have a history of allergic reaction attributed to compounds of
similar chemical or biologic composition to RO4929097

- Patients must be able to swallow tablets

- Patients must not have malabsorption syndrome or other condition that would interfere
with intestinal absorption of the agent

- Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin), are ineligible

- Patients must not be taking strong inducers or strong inhibitors of CYP3A4 at the
time of registration

- Patients must not be known to be serologically positive for Hepatitis A, B, or C, or
have a history of liver disease, other forms of hepatitis, or cirrhosis

- Patients must have an ECG within 28 days prior to registration. Patients must not
have a QTcF > 450 msec (males) or QTcF > 470 msec (females)

- Patients must not have symptomatic congestive heart failure or unstable angina
pectoris

- Patients with a history of torsades de pointes or any significant cardiac arrhythmia
(except asymptomatic unifocal ventricular premature beats or supraventricular
tachycardia easily controlled with oral medications) are excluded; any patient
requiring or expected to require antiarrhythmics or other therapy known to prolong
QTc is also excluded

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease free for five years

- Women of childbearing potential must have a negative pregnancy test within 14 days
prior to registration (the type of pregnancy test used is at the discretion of the
registering institution); female patients of childbearing potential include the
following:

- Patients with regular menses

- Patients, after menarche with amenorrhea, irregular cycles, or using a
contraceptive method that precludes withdrawal bleeding

- Women who have had tubal ligation

- Women must not be nursing due to possible harm to a nursing infant from the treatment
regimen

- All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines

- At the time of patient registration, the treating institution's name and ID number
must be provided to the Data Operations Center in Seattle in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered into the data base

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Outcome Time Frame:

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 6 months

Safety Issue:

No

Principal Investigator

Kim Margolin

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02040

NCT ID:

NCT01120275

Start Date:

October 2010

Completion Date:

Related Keywords:

  • Acral Lentiginous Malignant Melanoma
  • Lentigo Maligna Malignant Melanoma
  • Nodular Malignant Melanoma
  • Recurrent Melanoma
  • Solar Radiation-related Skin Melanoma
  • Stage IV Melanoma
  • Superficial Spreading Malignant Melanoma
  • Lentigo
  • Melanoma
  • Hutchinson's Melanotic Freckle

Name

Location

Louisiana State University New Orleans, Louisiana  70112-2282
University of Washington Medical Center Seattle, Washington  98195-6043
Hurley Medical Center Flint, Michigan  48503
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Loyola University Medical Center Maywood, Illinois  60153
Loma Linda University Medical Center Loma Linda, California  92354
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
University of Kansas Medical Center Kansas City, Kansas  66160-7353
William Beaumont Hospital Royal Oak, Michigan  48073
Wesley Medical Center Wichita, Kansas  67214
Group Health Cooperative Seattle, Washington  98112
Great Falls Clinic Great Falls, Montana  59405
Thompson Cancer Survival Center Knoxville, Tennessee  37916
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109
Munson Medical Center Traverse City, Michigan  49684
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Regional Medical Center Kalispell, Montana  59901
Adena Regional Medical Center Chillicothe, Ohio  54601
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Harborview Medical Center Seattle, Washington  98104
Cancer Care Northwest - Spokane South Spokane, Washington  99202
Welch Cancer Center Sheridan, Wyoming  82801
Good Samaritan Hospital - Cincinnati Cincinnati, Ohio  45220
University Medical Center of Southern Nevada Las Vegas, Nevada  89102
Poudre Valley Hospital Fort Collins, Colorado  80524
Salina Regional Health Center Salina, Kansas  67401
Mecosta County Medical Center Big Rapids, Michigan  49307
Saint Francis Medical Center Cape Girardeau, Missouri  63701
Iredell Memorial Hospital Statesville, North Carolina  28677
Grandview Hospital Dayton, Ohio  45405
Danville Regional Medical Center Danville, Virginia  24541
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Northeast Georgia Medical Center Gainesville, Georgia  30501
Miami Valley Hospital Dayton, Ohio  45409
Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Lawrence Memorial Hospital Lawrence, Kansas  66044
Menorah Medical Center Overland Park, Kansas  66209
Shawnee Mission Medical Center Shawnee Mission, Kansas  66204
North Kansas City Hospital Kansas City, Missouri  64116
Research Medical Center Kansas City, Missouri  64132
Saint Luke's East - Lee's Summit Lee's Summit, Missouri  64086
Liberty Hospital Liberty, Missouri  64068
Heartland Regional Medical Center Saint Joseph, Missouri  64506
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Mary Rutan Hospital Bellefontaine, Ohio  43311
Wayne Hospital Greenville, Ohio  45331
Knox Community Hospital Mount Vernon, Ohio  43050
Clinton Memorial Hospital Wilmington, Ohio  45177
Adventist Medical Center Portland, Oregon  97216
Wenatchee Valley Medical Center Wenatchee, Washington  98801-2028
Rocky Mountain Oncology Casper, Wyoming  82609
Greene Memorial Hospital Xenia, Ohio  45385
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Memorial Medical Center Springfield, Illinois  62781
McLeod Regional Medical Center Florence, South Carolina  29501
Wellmont Holston Valley Hospital and Medical Center Kingsport, Tennessee  37662
Metro Health Hospital Grand Rapids, Michigan  49506
Queen's Medical Center Honolulu, Hawaii  96813
Providence Hospital Mobile, Alabama  36608
Tahoe Forest Cancer Center Truckee, California  96161
Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701
Kapiolani Medical Center for Women and Children Honolulu, Hawaii  96826
Maui Memorial Medical Center Wailuku, Hawaii  96793
University of Rochester Rochester, New York  14642
Wayne State University Detroit, Michigan  48202
University of Arizona Health Sciences Center Tucson, Arizona  85724
Straub Clinic and Hospital Honolulu, Hawaii  96813
Riverside Methodist Hospital Columbus, Ohio  43214
Licking Memorial Hospital Newark, Ohio  43055-2899
Columbus CCOP Columbus, Ohio  43206
University of Kentucky Lexington, Kentucky  40536-0098
Montana Cancer Consortium CCOP Billings, Montana  59101
Virginia Mason CCOP Seattle, Washington  98101
UC Davis Comprehensive Cancer Center Sacramento, California  95817
Decatur Memorial Hospital Decatur, Illinois  62526
Montana Cancer Specialists Missoula, Montana  59807-7877
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
University of Cincinnati Cincinnati, Ohio  45267-0502
Hawaii Medical Center East Honolulu, Hawaii  96817
Castle Medical Center Kailua, Hawaii  96734
Hays Medical Center Hays, Kansas  67601
Saint Edward Mercy Medical Center Ft. Smith, Arkansas  72903
Fremont - Rideout Cancer Center Marysville, California  95901
Saint Mary's Hospital and Regional Medical Center Grand Junction, Colorado  81502
Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Oncare Hawaii Inc-POB II Honolulu, Hawaii  96813
Oncare Hawaii Inc-Kuakini Honolulu, Hawaii  96817
University of Hawaii Honolulu, Hawaii  96813
Saint Anthony's Health Alton, Illinois  62002
Good Samaritan Regional Medical Center Mt. Vernon, Illinois  62864
Saint Francis Hospital and Health Centers Beech Grove, Indiana  46107
Reid Hospital and Health Care Services Richmond, Indiana  47374
Genesis Medical Center - East Campus Davenport, Iowa  52803
Saint Francis Hospital and Medical Center - Topeka Topeka, Kansas  66606
Louisiana State University Sciences Center- Monroe Monroe, Louisiana  71210
Highland Clinic Shreveport, Louisiana  71105
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Saint Luke's Cancer Institute Kansas City, Missouri  64111
Saint Luke's Hospital of Kansas City Kansas City, Missouri  64111
Saint Joseph Health Center Kansas City, Missouri  64114
Liberty Radiation Oncology Clinic Kansas City, Missouri  64116
Truman Medical Center Kansas City, Missouri  64108
Saint Louis-Cape Girardeau CCOP Saint Louis, Missouri  63141
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield Springfield, Missouri  65802
Saint John's Hospital Springfield, Missouri  65804
Cox Medical Center Springfield, Missouri  65807
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Benefis Healthcare- Sletten Cancer Institute Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Glacier Oncology PLLC Kalispell, Montana  59901
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Mission Hospitals Inc Asheville, North Carolina  28801
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Margaret R Pardee Memorial Hospital Hendersonville, North Carolina  28791
Doctors Hospital Columbus, Ohio  43228
Grant Medical Center Columbus, Ohio  43215
Mount Carmel Health Center West Columbus, Ohio  43222
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Marietta Memorial Hospital Marietta, Ohio  45750
Upper Valley Medical Center Troy, Ohio  45373
Saint Ann's Hospital Westerville, Ohio  43081
Genesis HealthCare System Zanesville, Ohio  43701
AnMed Health Hospital Anderson, South Carolina  29621
Upstate Carolina CCOP Spartanburg, South Carolina  29303
Harrison Bremerton Hematology and Oncology Bremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLC Kennewick, Washington  99336
Evergreen Hospital Medical Center Kirkland, Washington  98033
Minor and James Medical PLLC Seattle, Washington  98104
The Polyclinic Seattle, Washington  98122
Swedish Medical Center-First Hill Seattle, Washington  98122-4307
University of California Medical Center At Irvine-Orange Campus Orange, California  92868
University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora, Colorado  80045
Denver Veterans Administration Medical Center Denver, Colorado  80220
University of Michigan University Hospital Ann Arbor, Michigan  48109
Central Care Cancer Center-Carrie J Babb Cancer Center Bolivar, Missouri  65613
Skaggs Cancer Center Branson, Missouri  65616
Skagit Valley Hospital Mt. Vernon, Washington  98273
Evergreen Hematology and Oncology PS Spokane, Washington  99218
Wilcox Memorial Hospital and Kauai Medical Clinic Lihue, Hawaii  96766-1099
Saint Luke's South Hospital Overland Park, Kansas  66213
Kansas City CCOP Prairie Village, Kansas  66208
Memorial Hospital Of Martinsville Martinsville, Virginia  24115
Cancer Care Center at Island Hospital Anacortes, Washington  98221
Highline Medical Center-Main Campus Burien, Washington  98166
Pacific Medical Center-First Hill Seattle, Washington  98104
United General Hospital Sedro-Woolley, Washington  98284
Fairbanks Memorial Hospital Fairbanks, Alaska  99701
Southwest Oncology Group San Antonio, Texas  78245
Genesys Regional Medical Center-West Flint Campus Flint, Michigan  48532
Via Christi Hospital-Pittsburg Pittsburg, Kansas  66762
PeaceHealth Saint Joseph Medical Center Bellingham, Washington  98225
Bronson Battle Creek Battle Creek, Michigan  49017
Springfield Regional Medical Center Springfield, Ohio  45505
Promise Regional Medical Center-Hutchinson Hutchinson, Kansas  65702
Saint Louis Cancer and Breast Institute-South City Saint Louis, Missouri  63109
Harrison Poulsbo Hematology and Oncology Poulsbo, Washington  98370