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
5 other identifiers
interventional
20
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2010
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2010
CompletedFirst Submitted
Initial submission to the registry
May 25, 2010
CompletedFirst Posted
Study publicly available on registry
May 26, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2014
CompletedDecember 23, 2014
November 1, 2014
4.3 years
May 25, 2010
December 22, 2014
Conditions
Outcome Measures
Primary Outcomes (2)
Recommended phase II dose of gamma-secretase inhibitor RO4929097 defined as the dose level at which < 1/6 patients experience dose-limiting toxicity as graded by the National Cancer Institute (NCI) CTCAE version 4.0
Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
42 days
Incidence of adverse events as graded by the NCI CTCAE version 4.0
Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
Up to 4 weeks post-treatment
Secondary Outcomes (3)
PK profiles for both drugs
On days 1, 10, 22, and 38 of course 1, and then on day 1 of courses 2-6
PD effects of gamma-secretase inhibitor RO4929097 when administered alone and in combined with cediranib maleate
On days 1 and 22 of course 1 and on day 1 of course 2
Preliminary antitumor efficacy
Up to 4 weeks post-treatment
Study Arms (1)
Treatment (cediranib maleate and RO4929097)
EXPERIMENTALPatients receive gamma-secretase inhibitor RO4929097 PO 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 only) 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
Interventions
Given PO
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- 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
- Total bilirubin normal =\< institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional upper limit of normal
- Serum creatinine \< institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- Left ventricular ejection fraction (LVEF) \>= 50% by echocardiogram (ECHO)/multi gated acquisition scan (MUGA)
- Urine dipstick for protein of less than +1; for +1 or greater than +1 proteinuria on 2 consecutive dipsticks taken no longer than 1 week apart, 24-hour urine for protein is necessary and should be \< 1 g/24 hours
- +13 more criteria
You may not qualify if:
- 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
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with RO4929097 with or without cediranib
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients with corrected QT interval (QTc) prolongation (defined as QTc interval \>= 450 msec in males and 470 msec in females, by Bazett correction) or other significant electrocardiogram (ECG) abnormalities (i.e. clinically significant arrhythmias requiring medication or conduction delays such as 2nd or 3rd degree atrioventricular blocks, etc) are ineligible
- History of risk factors for QT interval prolongation, including, but not limited to family or personal history of long QT syndrome, history of torsades de pointes, recurrent syncope without known etiology or sudden unexpected death
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sebastien Hotte
University Health Network-Princess Margaret Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 25, 2010
First Posted
May 26, 2010
Study Start
May 1, 2010
Primary Completion
September 1, 2014
Study Completion
September 1, 2014
Last Updated
December 23, 2014
Record last verified: 2014-11