Status:
COMPLETED
Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Endometrial Papillary Serous Carcinoma
Recurrent Endometrial Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This phase I trial is studying the side effects and best dose of giving gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temsirolimus together in treating patients with advanced solid ...
Detailed Description
PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) and safety profile of temsirolimus in combination with RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Meets one of the following sets of criteria:
- Dose-escalation group:
- Histologically and/or cytologically confirmed solid malignancy
- Metastatic or unresectable disease
- Disease for which standard curative or palliative measures do not exist or are no longer effective
- Expansion group:
- Histologically and/or cytologically confirmed endometrial (endometrioid, uterine papillary serious carcinoma, or carcinosarcoma) or renal cell cancer
- Metastatic or unresectable disease
- Disease for which standard curative or palliative measures do not exist or are no longer effective
- Measurable or non-measurable disease
- Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
- No known brain metastases
- ECOG performance status (PS) 0-1 (Karnofsky PS 70-100%)
- Life expectancy \> 12 weeks
- Leukocytes ≥ 3,000/mm\^3
- ANC ≥ 1,500/mm\^3
- Platelet count ≥ 100,000/mm\^3
- Hemoglobin ≥ 90 g/L (or ≥ 9 g/dL)
- Total bilirubin normal
- AST/ALT ≤ 2.5 times upper limit of normal
- Serum creatinine normal OR creatine clearance ≥ 60 mL/min
- Fasting cholesterol ≤ 350 mg/dL (9.0 mmol/L)
- Fasting triglycerides ≤ 400 mg/dL (4.56 mmol/L)
- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation
- Note: it is acceptable to use corrected calcium when interpreting calcium levels
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use two effective forms of contraception (i.e., barrier contraception and one other method of contraception) for ≥ 4 weeks before, during, and for ≥ 12 months after completion of study therapy
- Able to swallow medication
- No malabsorption syndrome or other condition that would interfere with intestinal absorption
- No diarrhea ≥ grade 2 that is not under control with standard anti-diarrhea medications
- No uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable anginal pectoris
- Cardiac arrhythmia other than chronic, stable atrial fibrillation
- Psychiatric illness or social situations that would limit compliance with study medications
- QTc ≤ 450 msec in males and a QTc ≤ 470 msec in females, as measured by ECG using Bazett formula
- No history of risk factors for QT interval prolongation including, but not limited to, a family or personal history of any of the following:
- Long QT syndrome
- Torsades de pointes
- Recurrent syncope without known etiology
- Sudden unexpected death
- No pre-existing significant pulmonary infiltrates of unknown origin
- No serologic positivity for hepatitis A, B, or C or history of liver disease or other forms of hepatitis or cirrhosis
- No HIV-positive patients on combination antiretroviral therapy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or temsirolimus
- Female patients may not donate ova during or after study treatment
- Male patients may not donate sperm during and for ≥ 12 months after completion of study treatment
- Patients may not donate blood during and for ≥ 12 months after completion of study treatment
- Any number of prior therapies allowed
- Recovered from side effects of previous systemic anticancer therapy to \< CTCAE grade 2 toxicity (except alopecia)
- Concurrent leuteinizing hormone-releasing hormone agonist allowed in patients with castration-resistant prostate cancer
- No prior gamma-secretase inhibitor or any inhibitor of the PI3K/Akt/mTOR pathway
- At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for carmustine, nitrosoureas, or mitomycin C)
- Exceptions may be made for low-dose, non-myelosuppressive radiotherapy for symptomatic palliation
- No other concurrent investigational agents
- No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
- No concurrent medications that are strong inducers, inhibitors, or substrates of CYP3A4
- No antiarrhythmics or other concurrent medications with known potential to prolong QT interval
- No concurrent food that may interfere with the metabolism of gamma-secretase inhibitor RO4929097, including grapefruit or grapefruit juice
- No other concurrent anticancer agents or therapies
Exclusion
Key Trial Info
Start Date :
August 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 1 2013
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT01198184
Start Date
August 1 2010
End Date
October 1 2013
Last Update
May 30 2014
Active Locations (2)
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1
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
2
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9