RO4929097 and Capecitabine in Treating Patients With Refractory Solid Tumors
A Phase 1 Study of RO4929097 (NSC749225) in Combination With Capecitabine in Refractory Solid Tumors
7 other identifiers
interventional
30
2 countries
2
Brief Summary
This phase I clinical trial is studying the side effects and best dose of RO4929097 when given together with capecitabine in treating patients with refractory solid tumors. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving RO4929097 together with chemotherapy may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 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
June 1, 2010
CompletedFirst Submitted
Initial submission to the registry
July 7, 2010
CompletedFirst Posted
Study publicly available on registry
July 8, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2012
CompletedNovember 7, 2014
June 1, 2014
2.2 years
July 7, 2010
November 6, 2014
Conditions
Outcome Measures
Primary Outcomes (3)
MTD of RO4929097 and capecitabine, defined as that dose level at which less than one-third of patients experience a dose-limiting toxicity (DLT) graded according to NCI CTCAE version 4.0 (Part 1)
Up to 21 days
Incidence of adverse events graded according to NCI CTCAE version 4.0 (Part 1)
Possible adverse events will be reported in tabular format. To determine the severity of the reaction for adverse event reporting, the NCI CTCAE version 4.0 will be used.
Up to 30 days after completion of study treatment
Incidence of adverse events graded according to NCI CTCAE version 4.0 (Parts 2a and 2b)
Possible adverse events will be reported in tabular format. To determine the severity of the reaction for adverse event reporting, the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used.
Up to 24 months
Secondary Outcomes (6)
Confirmed anti-tumor response rate validated by the RECIST (Part 1)
Up to 30 days after completion of study treatment
Changes in the expression of Notch1 signaling pathway members (Part 1)
From baseline to 30 days after completion of study treatment
Pharmacokinetics of the combination of RO4929097 and capecitabine, including Cmax, Tmax, AUC, t1/2, and CL (Part 1)
Baseline on day 1 of course 1; baseline and 1, 2, 3, 4, 8, 12, 16, and 24 hours on days 3 and 10 of course 1; and baseline on day 1 of all subsequent courses
PFS (Parts 2a and 2b)
Up to 24 months
OS (Part 2a and 2b)
Number of days from the day of first RO4929097 and capecitabine administration to the patient's death, assessed up to 24 months
- +1 more secondary outcomes
Study Arms (1)
Treatment
EXPERIMENTALPatients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given orally
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed advanced or metastatic solid tumor; patients with lymphoma will be eligible
- Patients must have measurable disease, 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 CT scan
- Patients must be at least 4 weeks since prior chemotherapy, 6 weeks if the last regimen included BCNU or mitomycin C; prior radiation is allowed as long as the radiation was completed 4 weeks prior to study treatment and no more than 35% of marrow irradiated
- Life expectancy of greater than 3 months
- 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 within normal institutional limits
- AST (SGOT)/ALT (SGPT) =\< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal; a 24 hour urine collection and creatinine clearance can be measured if indicated
- Treated, stable brain metastases are allowed; patients must be four weeks from radiation with stable brain imaging and off any medications used to treat brain metastases, excepting those anti-epileptics not metabolized by cytochrome P450
- Women of childbearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately
- Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of RO4929097 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of RO4929097; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing RO4929097, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of RO4929097
- +17 more criteria
You may not qualify if:
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or capecitabine
- Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible
- 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, 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, and a history of torsades de pointes or other significant 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
- HIV-positive patients, who are not on anti-retroviral therapy but have CD4 cells less than 200, should be excluded; HIV-positive patients are eligible if they are on HAART (highly active anti-retroviral therapy) which are not CYP3A4 substrates, inducers and/or inhibitors and meet all other criteria
- Cardiovascular: baseline QTcF \> 450 msec
- Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency enzyme are excluded
- Patients who have not recovered to \< CTCAE grade 2 toxicities related to prior therapy are not eligible to participate in this study
- A requirement for antiarrhythmics or other medications known to prolong QTc
- PART2B (MTD EXPANSION BREAST CANCER):
- Patients may not have had more than 1 prior cytotoxic chemotherapy for metastatic disease; prior endocrine or immunotherapy regimens for metastatic disease will not be counted as cytotoxic
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Noelle LoConte
University of Wisconsin, Madison
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
July 7, 2010
First Posted
July 8, 2010
Study Start
June 1, 2010
Primary Completion
August 1, 2012
Last Updated
November 7, 2014
Record last verified: 2014-06