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Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors | Clinical Trials | Clareo Health

COMPLETEDPHASE1

Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

A Phase 1, Pharmacokinetic and Pharmacodynamic Study of the Combination of RO4929097 and Cediranib in Patients With Advanced Solid Tumors

NCT01131234•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I clinical trial is studying the side effects and best dose of giving gamma-secretase inhibitor RO4929097 and cediranib maleate together in treating patients with advanced solid tumors. Gamma-secretase inhibitor RO4929097 and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate also may stop the growth of tumor cells by blocking blood flow to the tumor.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the tolerability, maximum tolerated dose (equivalent to the recommended phase II dose), and safety profile of RO4929097 (gamma-secretase inhibitor RO4929097) in combination with cediranib (cediranib maleate) in patients with advanced malignancies. SECONDARY OBJECTIVES: I. To obtain pharmacokinetic (PK) profiles for RO4929097 when administered alone and for RO492907 and cediranib in combination, in order to evaluate for interactive effects in PK (if any) between these two agents. II. To evaluate pharmacodynamic (PD) effects of RO492907 when administered alone and in combination, with the goal of identifying potential predictive and PD markers that need further exploration and validation in future trials. III. To assess for preliminary antitumor efficacy of this drug combination, especially in breast cancer, malignant melanoma, colorectal cancer, pancreatic cancer, kidney cancer, high grade glioma, non-small-cell lung cancer, and ovarian cancer. OUTLINE: This is a dose-escalation study. Patients receive gamma-secretase inhibitor RO4929097 orally (PO) once daily (QD) on days 1-3, 8-10, and 15-17 (days 1-3, 8-10, 15-17 22-24, 29-31, and 36-38 of course 1) and cediranib maleate PO QD on days 1-21 (days 22-42 course 1 only). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Dose-escalation cohorts: Patients must have histologically and/or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; expansion cohort: patients must have histologically and/or cytologically confirmed breast cancer, malignant melanoma, colorectal cancer, pancreatic cancer, kidney cancer, high grade glioma, non-small-cell lung cancer, or ovarian cancer
•Patients must have measurable or non-measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral computed tomography (CT) scan; measurable disease is not required to participate in this trial
•No limitation on prior therapy; however, there must be at least a 4 week interval between initiation of study treatment and any prior radiotherapy or systemic therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy for symptomatic palliation; please contact the Princess Margaret Hospital (PMH) Phase I Consortium Central Office coordinator or the Principal Investigator if any questions arise about interpretation of this criterion
•Life expectancy of greater than 12 weeks
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
•Leukocytes \>= 3.0 x 10\^9/L
•Absolute neutrophil count \>= 1.5 x 10\^9/L
•Platelets \>= 100 x 10\^9/L
•Hemoglobin \>= 90 g/L (or \>= 9 g/dL)
•International normalized ratio (INR) =\< 1.3
+21 more criteria

Exclusion Criteria

•Patients who have had systemic therapy or radiotherapy or major surgery within 4 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 4 weeks earlier
•Patients may not be receiving any other investigational agents within the past 30 days or have been previously treated with a gamma-secretase inhibitor and/or cediranib; exposure to other angiogenesis inhibitors (e.g. sorafenib, bevacizumab) is acceptable
•Patients with any meningeal metastases or untreated known brain metastases should be excluded from this clinical trial; patients with treated brain metastasis with radiologic and clinical evidence of stability, with no evidence of cavitation or hemorrhage in the brain lesions, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization)
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 and/or cediranib used in the study
•Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible (except low dose warfarin for prophylaxis for central catheters)
•Patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should be switched to alternative medications to minimize any potential risk; if such patients cannot be switched to alternative medications, they will be ineligible to participate in this study
•Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, active peptic ulcer disease, short gut syndrome, malabsorption syndrome of any type, total or partial bowel obstruction or inability to tolerate oral medications) that potentially impairs their ability to swallow or absorb are excluded
•Patients who are serologically positive for hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible
•Patients with uncontrolled 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
•* Note: it is acceptable to use corrected calcium when interpreting calcium levels
+14 more criteria

Locations (2)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Key Dates

Start Date

May 1, 2010

Primary Completion Date

September 1, 2014

Completion Date

September 1, 2014

Last Updated

December 23, 2014

Enrollment

ACTUAL participants

Conditions

Adult Anaplastic AstrocytomaAdult Anaplastic EpendymomaAdult Anaplastic OligodendrogliomaAdult Brain Stem GliomaAdult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaAdult Mixed GliomaAdult Solid NeoplasmMale Breast CarcinomaRecurrent Adult Brain NeoplasmRecurrent Breast CarcinomaRecurrent Colon CarcinomaRecurrent MelanomaRecurrent Non-Small Cell Lung CarcinomaRecurrent Ovarian CarcinomaRecurrent Ovarian Germ Cell TumorRecurrent Pancreatic CarcinomaRecurrent Rectal CarcinomaRecurrent Renal Cell CarcinomaStage III Pancreatic CancerStage III Renal Cell CancerStage IIIA Colon CancerStage IIIA Non-Small Cell Lung CancerStage IIIA Ovarian CancerStage IIIA Ovarian Germ Cell TumorStage IIIA Rectal CancerStage IIIA Skin MelanomaStage IIIB Breast CancerStage IIIB Colon CancerStage IIIB Non-Small Cell Lung CancerStage IIIB Ovarian CancerStage IIIB Ovarian Germ Cell TumorStage IIIB Rectal CancerStage IIIB Skin MelanomaStage IIIC Breast CancerStage IIIC Colon CancerStage IIIC Ovarian CancerStage IIIC Ovarian Germ Cell TumorStage IIIC Rectal CancerStage IIIC Skin MelanomaStage IV Breast CancerStage IV Non-Small Cell Lung CancerStage IV Ovarian CancerStage IV Ovarian Germ Cell TumorStage IV Pancreatic CancerStage IV Renal Cell CancerStage IV Skin MelanomaStage IVA Colon CancerStage IVA Rectal CancerStage IVB Colon CancerStage IVB Rectal Cancer

Interventions

Gamma-Secretase Inhibitor RO4929097

DRUG

Cediranib Maleate

DRUG

Pharmacological Study

OTHER

Laboratory Biomarker Analysis

OTHER

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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: December 23, 2014Data 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 Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

Inclusion Criteria

Exclusion Criteria

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