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

Stage IV Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01120275
• Other study ID #: NCI-2011-02040
• Secondary ID: NCI-2011-02040SW
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 7, 2010
• Last updated: June 9, 2014
• Start date: October 2010

Study information

• Verified date: June 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Acral Lentiginous Malignant Melanoma
• Lentigo Maligna Malignant Melanoma
• Melanoma
• Nodular Malignant Melanoma
• Recurrent Melanoma
• Solar Radiation-related Skin Melanoma
• Stage IV Melanoma
• Superficial Spreading Malignant Melanoma

Intervention

Drug:
• gamma-secretase/Notch signalling pathway inhibitor RO4929097
Given PO

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Pali Momi Medical Center	Aiea	Hawaii
United States	Saint Anthony's Health	Alton	Illinois
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan	Ann Arbor	Michigan
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	CoxHealth Cancer Center	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Columbus CCOP	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Denver Veterans Administration Medical Center	Denver	Colorado
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Saint Edward Mercy Medical Center	Ft. Smith	Arkansas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Hays Medical Center	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Promise Regional Medical Center-Hutchinson	Hutchinson	Kansas
United States	Allegiance Health	Jackson	Michigan
United States	Castle Medical Center	Kailua	Hawaii
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Evergreen Hospital Medical Center	Kirkland	Washington
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky	Lexington	Kentucky
United States	Liberty Hospital	Liberty	Missouri
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Providence Hospital	Mobile	Alabama
United States	Louisiana State University Sciences Center- Monroe	Monroe	Louisiana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Licking Memorial Hospital	Newark	Ohio
United States	University of California Medical Center At Irvine-Orange Campus	Orange	California
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Via Christi Hospital-Pittsburg	Pittsburg	Kansas
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	SWOG	Portland	Oregon
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City CCOP	Prairie Village	Kansas
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	University of California at Davis Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason CCOP	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Highland Clinic	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Upstate Carolina CCOP	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Tahoe Forest Cancer Center	Truckee	California
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	Maui Memorial Medical Center	Wailuku	Hawaii
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Wesley Medical Center	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis HealthCare System	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		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	No
Primary	Overall survival		Up to 1 year	No
Secondary	Response rate (confirmed and unconfirmed complete or partial response)		Up to 3 years	No
Secondary	Toxicity rates as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		Up to 3 years	Yes