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

COMPLETEDPHASE1/PHASE2

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

Phase Ib/II Study of the Gamma-Secretase Inhibitor (GSI) RO4929097 in Combination With Cisplatin, Vinblastine, and Temozolomide (CVT) in Patients With Metastatic Melanoma

NCT01196416•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase Ib/II trial studies the side effects and best dose of gamma-secretase/Notch signalling pathway inhibitor RO4929097 when given together with cisplatin, vinblastine, and temozolomide and to see how well they work in treating patients with recurrent or metastatic 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. Drugs used in chemotherapy, such as cisplatin, vinblastine, and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gamma-secretase/Notch signalling pathway inhibitor RO4929097 together with combination chemotherapy may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES: I. To characterize the safety and tolerability of daily RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) administered orally daily in combination with CVT (starting dose: cisplatin 25 mg/m\^2 intravenous \[IV\] daily x 3; vinblastine 1.2 mg/m\^2 IV daily x 3, and temozolomide \[TMZ\] 150 mg/m\^2 orally \[PO\] daily x 5) administered on an every 21 day schedule. (Phase Ib) II. To determine the maximum-tolerated dose (MTD) of RO4929097 with CVT in patients with metastatic melanoma with correlative biomarkers for Notch pathway signaling and gamma secretase enzyme activity. (Phase Ib) III. Based on the MTD from the phase Ib study, to conduct a phase II trial and to determine the response rate and overall survival. (Phase II) SECONDARY OBJECTIVES: I. To describe the pharmacokinetics and pharmacodynamics of the combination of RO4929097 and temozolomide. (Phase Ib) II. To obtain tissue biopsy for correlative studies before the initiation of therapy and one week after treatment with RO4929097 and CVT. (Phase Ib and II) III. To determine the progression-free survival of patients treated at the phase II dose. (Phase II) OUTLINE: This is phase I dose-escalation study of gamma-secretase inhibitor RO4929097, followed by a phase II study. Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO once daily (QD) on days 1-21, cisplatin IV over 30 minutes and vinblastine IV over 30 minutes on days 1-3, and temozolomide PO QD on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease continue to receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temozolomide as above in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 24 months.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically or cytologically Memorial Sloan Kettering Cancer Center (MSKCC) confirmed recurrent or metastatic melanoma
•All Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \> 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or \> 20 mm when measured by chest x-ray; lymph nodes must be \> 15 mm in short axis when measured by CT or MRI
•Patients may have had up to one prior systemic therapy for recurrent or metastatic disease, but cannot have previously been treated with cisplatin, vinblastine, temozolomide, dacarbazine, or a gamma-secretase inhibitor; at least 3 weeks must have elapsed since the last dose of systemic therapy; for small molecule targeted therapy, at least 5 half-lives must have elapsed; at least 6 weeks must have elapsed if the last regimen included carmustine (BCNU) or mitomycin C or an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody
•Life expectancy of greater than 3 months
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
•Hemoglobin \>= 9 g/dL
•Leukocytes \>= 3,000/mcL
•Absolute neutrophil count \>= 1,500/mcL
•Platelets \>= 100,000/mcL
•Total bilirubin =\< institutional upper limit of normal
+14 more criteria

Exclusion Criteria

•Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
•Patients may not be receiving any other investigational agents
•Patients with known brain metastases are excluded unless brain metastases have been resected or successfully treated with stereotactic radiosurgery and the patient has been free from central nervous system (CNS) recurrence or progression for 3 months
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or other agents used in the study
•Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible
•Preclinical studies indicate that RO4929097 is a substrate of CYP3A4 and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; the following medications with strong potential for interaction are not allowed: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone
•Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption
•Patients must be able to swallow tablets
•Patients who are serologically positive for hepatitis A, B or C, and have an active infection, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible
•Patients with uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia or hypokalemia, defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
+4 more criteria

Locations (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Key Dates

Start Date

August 1, 2010

Primary Completion Date

August 1, 2015

Completion Date

August 1, 2015

Last Updated

November 18, 2019

Enrollment

ACTUAL participants

Conditions

Recurrent MelanomaStage IV Skin Melanoma

Interventions

Cisplatin

DRUG

Gamma-Secretase Inhibitor RO4929097

DRUG

Laboratory Biomarker Analysis

OTHER

Pharmacological Study

OTHER

Temozolomide

DRUG

Vinblastine Sulfate

DRUG

Dinaciclib in Treating Patients With Stage IV Melanoma

NCT00937937

Acral Lentiginous MelanomaCutaneous Nodular Melanoma+5 more

View study

ACTIVE_NOT_RECRUITINGPHASE1

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

NCT01303341

Advanced Malignant Solid NeoplasmRecurrent Melanoma+6 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 18, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Dinaciclib in Treating Patients With Stage IV Melanoma

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

RO4929097 and Whole-Brain Radiation Therapy or Stereotactic Radiosurgery in Treating Patients With Brain Metastases From Breast Cancer