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

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

Sponsors

Lead Sponsor: National Cancer Institute (NCI)

Source National Cancer Institute (NCI)
Brief Summary

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.

Detailed Description

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.

Overall Status Terminated
Start Date 2010-10-01
Completion Date 2015-08-01
Primary Completion Date 2013-05-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression-free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Disease assessments were performed every 6 weeks, up to 3 years.
Overall Survival Weekly, up to 3 years.
Secondary Outcome
Measure Time Frame
Percentage of Participants With Confirmed and Unconfirmed Complete or Partial Response Disease assessments for response were performed every 6 weeks, up to 3 years
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Toxicity assessment was evaluated at least every 3 weeks at the beginning of each cycle, up to 3 years
Enrollment 36
Condition
Intervention

Intervention Type: Drug

Intervention Name: gamma-secretase/Notch signalling pathway inhibitor RO4929097

Description: Given PO

Arm Group Label: Treatment (gamma-secretase inhibitor RO4929097)

Intervention Type: Other

Intervention Name: laboratory biomarker analysis

Description: Correlative studies

Arm Group Label: Treatment (gamma-secretase inhibitor RO4929097)

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

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

United States

Verification Date

2016-05-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Treatment (gamma-secretase inhibitor RO4929097)

Type: Experimental

Description: 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.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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