Home
Clinical Trials
Gamma-Secretase/Notch Signall...

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

NCT ID: NCT01120275

Last Updated: 2016-06-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2015-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery

NCT01216787

Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma

WITHDRAWN PHASE2

Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Combination With Cisplatin, Vinblastine, and Temozolomide in Treating Patients With Recurrent or Metastatic Melanoma

NCT01196416

Recurrent Melanoma Stage IV Skin Melanoma

COMPLETED PHASE1/PHASE2

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

NCT01198184

Endometrial Papillary Serous Carcinoma Recurrent Endometrial Carcinoma Recurrent Renal Cell Cancer +5 more

COMPLETED PHASE1

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced Solid Tumors

NCT01218620

Adult Solid Neoplasm

COMPLETED PHASE1

Sorafenib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

NCT00119249

Stage III Melanoma Stage IV Melanoma

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

gamma-secretase/Notch signalling pathway inhibitor RO4929097

Intervention Type DRUG

Given PO

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

gamma-secretase/Notch signalling pathway inhibitor RO4929097

Given PO

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

R4733 RO4929097

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kim Margolin

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, United States

Site Status

Wayne Hospital

Greenville, Ohio, United States

Site Status

Kettering Medical Center

Kettering, Ohio, United States

Site Status

Fairfield Medical Center

Lancaster, Ohio, United States

Site Status

Marietta Memorial Hospital

Marietta, Ohio, United States

Site Status

Knox Community Hospital

Mount Vernon, Ohio, United States

Site Status

Licking Memorial Hospital

Newark, Ohio, United States

Site Status

Springfield Regional Medical Center

Springfield, Ohio, United States

Site Status

Upper Valley Medical Center

Troy, Ohio, United States

Site Status

Saint Ann's Hospital

Westerville, Ohio, United States

Site Status

Clinton Memorial Hospital

Wilmington, Ohio, United States

Site Status

Greene Memorial Hospital

Xenia, Ohio, United States

Site Status

Genesis HealthCare System

Zanesville, Ohio, United States

Site Status

Adventist Medical Center

Portland, Oregon, United States

Site Status

SWOG

Portland, Oregon, United States

Site Status

AnMed Health Hospital

Anderson, South Carolina, United States

Site Status

McLeod Regional Medical Center

Florence, South Carolina, United States

Site Status

Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Site Status

Upstate Carolina CCOP

Spartanburg, South Carolina, United States

Site Status

Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, United States

Site Status

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Site Status

Danville Regional Medical Center

Danville, Virginia, United States

Site Status

Memorial Hospital Of Martinsville

Martinsville, Virginia, United States

Site Status

Cancer Care Center at Island Hospital

Anacortes, Washington, United States

Site Status

PeaceHealth Saint Joseph Medical Center

Bellingham, Washington, United States

Site Status

Harrison HealthPartners Hematology and Oncology-Bremerton

Bremerton, Washington, United States

Site Status

Highline Medical Center-Main Campus

Burien, Washington, United States

Site Status

Columbia Basin Hematology and Oncology PLLC

Kennewick, Washington, United States

Site Status

Evergreen Hospital Medical Center

Kirkland, Washington, United States

Site Status

Skagit Valley Hospital

Mount Vernon, Washington, United States

Site Status