Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: May 7, 2010
Last updated: June 9, 2014
Last verified: June 2014

This phase II trial is studying how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 works in treating patients with stage IV melanoma. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
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
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ 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 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (confirmed and unconfirmed complete or partial response) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Toxicity rates as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: October 2010
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gamma-secretase inhibitor RO4929097)
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Given PO
Other Names:
  • R4733
  • RO4929097
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


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).


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.


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

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
  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 identifier: NCT01120275

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United States, Alabama
Providence Hospital
Mobile, Alabama, United States, 36608
United States, Alaska
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States, 99701
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Arkansas
Saint Edward Mercy Medical Center
Ft. Smith, Arkansas, United States, 72903
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Fremont - Rideout Cancer Center
Marysville, California, United States, 95901
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
Tahoe Forest Cancer Center
Truckee, California, United States, 96161
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
Denver Veterans Administration Medical Center
Denver, Colorado, United States, 80220
Poudre Valley Hospital
Fort Collins, Colorado, United States, 80524
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, United States, 81502
United States, Connecticut
Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Hawaii
Pali Momi Medical Center
Aiea, Hawaii, United States, 96701
Oncare Hawaii Inc-POB II
Honolulu, Hawaii, United States, 96813
Oncare Hawaii Inc-Kuakini
Honolulu, Hawaii, United States, 96817
Queen's Medical Center
Honolulu, Hawaii, United States, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, United States, 96813
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, United States, 96817
University of Hawaii
Honolulu, Hawaii, United States, 96813
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96826
Castle Medical Center
Kailua, Hawaii, United States, 96734
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, United States, 96766
Maui Memorial Medical Center
Wailuku, Hawaii, United States, 96793
United States, Illinois
Saint Anthony's Health
Alton, Illinois, United States, 62002
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Good Samaritan Regional Health Center
Mount Vernon, Illinois, United States, 62864
Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
Saint Francis Hospital and Health Centers
Beech Grove, Indiana, United States, 46107
Reid Hospital and Health Care Services
Richmond, Indiana, United States, 47374
United States, Iowa
Genesis Medical Center - East Campus
Davenport, Iowa, United States, 52803
United States, Kansas
Hays Medical Center
Hays, Kansas, United States, 67601
Promise Regional Medical Center-Hutchinson
Hutchinson, Kansas, United States, 65702
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Saint Luke's South Hospital
Overland Park, Kansas, United States, 66213
Via Christi Hospital-Pittsburg
Pittsburg, Kansas, United States, 66762
Kansas City CCOP
Prairie Village, Kansas, United States, 66208
Salina Regional Health Center
Salina, Kansas, United States, 67401
Shawnee Mission Medical Center
Shawnee Mission, Kansas, United States, 66204
Saint Francis Hospital and Medical Center - Topeka
Topeka, Kansas, United States, 66606
Wesley Medical Center
Wichita, Kansas, United States, 67214
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Louisiana State University Sciences Center- Monroe
Monroe, Louisiana, United States, 71210
Highland Clinic
Shreveport, Louisiana, United States, 71105
Louisiana State University Health Sciences Center Shreveport
Shreveport, Louisiana, United States, 71130
United States, Maryland
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Michigan
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, United States, 48106
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
University of Michigan
Ann Arbor, Michigan, United States, 48109
Bronson Battle Creek
Battle Creek, Michigan, United States, 49017
Spectrum Health Big Rapids Hospital
Big Rapids, Michigan, United States, 49307
Oakwood Hospital
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
Hurley Medical Center
Flint, Michigan, United States, 48502
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
Mercy Health Saint Mary's
Grand Rapids, Michigan, United States, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Allegiance Health
Jackson, Michigan, United States, 49201
Sparrow Hospital
Lansing, Michigan, United States, 48912
Saint Mary Mercy Hospital
Livonia, Michigan, United States, 48154
Mercy Health Mercy Campus
Muskegon, Michigan, United States, 49444
Saint Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Saint Joseph Mercy Port Huron
Port Huron, Michigan, United States, 48060
William Beaumont Hospital-Royal Oak
Royal Oak, Michigan, United States, 48073
Saint Mary's of Michigan
Saginaw, Michigan, United States, 48601
Munson Medical Center
Traverse City, Michigan, United States, 49684
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States, 48093
Metro Health Hospital
Wyoming, Michigan, United States, 49519
United States, Missouri
Central Care Cancer Center-Carrie J Babb Cancer Center
Bolivar, Missouri, United States, 65613
CoxHealth Cancer Center
Branson, Missouri, United States, 65616
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63703
Saint Luke's Cancer Institute
Kansas City, Missouri, United States, 64111
Research Medical Center
Kansas City, Missouri, United States, 64132
Saint Joseph Health Center
Kansas City, Missouri, United States, 64114
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Truman Medical Center
Kansas City, Missouri, United States, 64108
North Kansas City Hospital
Kansas City, Missouri, United States, 64116
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, United States, 64086
Liberty Hospital
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
Saint Louis-Cape Girardeau CCOP
Saint Louis, Missouri, United States, 63141
Saint Louis Cancer and Breast Institute-South City
Saint Louis, Missouri, United States, 63109
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
CoxHealth South Hospital
Springfield, Missouri, United States, 65807
Mercy Hospital Springfield
Springfield, Missouri, United States, 65804
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65802
United States, Montana
Hematology-Oncology Centers of the Northern Rockies PC
Billings, Montana, United States, 59102
Montana Cancer Consortium CCOP
Billings, Montana, United States, 59101
Saint Vincent Healthcare
Billings, Montana, United States, 59101
Billings Clinic
Billings, Montana, United States, 59107-7000
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, United States, 59405
Great Falls Clinic
Great Falls, Montana, United States, 59405
Saint Peter's Community Hospital
Helena, Montana, United States, 59601
Glacier Oncology PLLC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Saint Patrick Hospital - Community Hospital
Missoula, Montana, United States, 59802
Montana Cancer Specialists
Missoula, Montana, United States, 59802
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
University Medical Center of Southern Nevada
Las Vegas, Nevada, United States, 89102
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Mission Hospital-Memorial Campus
Asheville, North Carolina, United States, 28801
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States, 28204
Wayne Memorial Hospital
Goldsboro, North Carolina, United States, 27534
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
United States, Ohio
Mary Rutan Hospital
Bellefontaine, Ohio, United States, 43311
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, United States, 45220
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Doctors Hospital
Columbus, Ohio, United States, 43228
Columbus CCOP
Columbus, Ohio, United States, 43215
Grant Medical Center
Columbus, Ohio, United States, 43215
Mount Carmel Health Center West
Columbus, Ohio, United States, 43222
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Dayton CCOP
Dayton, Ohio, United States, 45420
Good Samaritan Hospital - Dayton
Dayton, Ohio, United States, 45406
Grandview Hospital
Dayton, Ohio, United States, 45405
Miami Valley Hospital
Dayton, Ohio, United States, 45409
Samaritan North Health Center
Dayton, Ohio, United States, 45415
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Blanchard Valley Hospital
Findlay, Ohio, United States, 45840
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Wayne Hospital
Greenville, Ohio, United States, 45331
Kettering Medical Center
Kettering, Ohio, United States, 45429
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
Knox Community Hospital
Mount Vernon, Ohio, United States, 43050
Licking Memorial Hospital
Newark, Ohio, United States, 43055
Springfield Regional Medical Center
Springfield, Ohio, United States, 45505
Upper Valley Medical Center
Troy, Ohio, United States, 45373
Saint Ann's Hospital
Westerville, Ohio, United States, 43081
Clinton Memorial Hospital
Wilmington, Ohio, United States, 45177
Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Genesis HealthCare System
Zanesville, Ohio, United States, 43701
United States, Oregon
Adventist Medical Center
Portland, Oregon, United States, 97216
Portland, Oregon, United States, 97239
United States, South Carolina
AnMed Health Hospital
Anderson, South Carolina, United States, 29621
McLeod Regional Medical Center
Florence, South Carolina, United States, 29506
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
Upstate Carolina CCOP
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, United States, 37660
Thompson Cancer Survival Center
Knoxville, Tennessee, United States, 37916
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
Memorial Hospital Of Martinsville
Martinsville, Virginia, United States, 24115
United States, Washington
Cancer Care Center at Island Hospital
Anacortes, Washington, United States, 98221
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, United States, 98225
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, United States, 98310
Highline Medical Center-Main Campus
Burien, Washington, United States, 98166
Columbia Basin Hematology and Oncology PLLC
Kennewick, Washington, United States, 99336
Evergreen Hospital Medical Center
Kirkland, Washington, United States, 98033
Skagit Valley Hospital
Mount Vernon, Washington, United States, 98274
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, United States, 98370
Virginia Mason CCOP
Seattle, Washington, United States, 98101
Group Health Cooperative-Seattle
Seattle, Washington, United States, 98112
Harborview Medical Center
Seattle, Washington, United States, 98104
Minor and James Medical PLLC
Seattle, Washington, United States, 98104
Pacific Medical Center-First Hill
Seattle, Washington, United States, 98104
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122-4307
The Polyclinic
Seattle, Washington, United States, 98122
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
United General Hospital
Sedro-Woolley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Evergreen Hematology and Oncology PS
Spokane, Washington, United States, 99218
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801
United States, Wyoming
Rocky Mountain Oncology
Casper, Wyoming, United States, 82609
Welch Cancer Center
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Principal Investigator: Kim Margolin Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01120275     History of Changes
Other Study ID Numbers: NCI-2011-02040, NCI-2011-02040, SWOG-S0933, CDR0000671815, S0933, S0933, U10CA032102
Study First Received: May 7, 2010
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas processed this record on February 27, 2015