PHASE I STUDY OF CARBOPLATIN, PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) AND EVEROLIMUS IN PATIENTS WITH PLATINUM-SENSITIVE EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER IN FIRST RELAPSE
| City: |
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Philadelphia |
| State: |
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Pennsylvania |
| Zip Code: |
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19111 |
| Conditions: |
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Fallopian Tube Cancer - Peritoneal Cavity Cancer - Recurrent Ovarian Epithelial Cancer |
| Purpose: |
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and pegylated liposomal
doxorubicin hydrochloride (PLD) work in different ways to stop the growth of tumor cells,
either by killing the cells or by stopping them from dividing. Everolimus may stop the
growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving
carboplatin and PLD together with everolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when
given together with carboplatin and PLD in treating patients with relapsed ovarian
epithelial, fallopian tube, or peritoneal cavity cancer
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| Study Summary: |
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PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of RAD001 (everolimus) in combination with
carboplatin and PLD.
SECONDARY OBJECTIVES:
I. Determine safety/tolerability of the three drug combination of carboplatin, PLD and
RAD001 (everolimus).
II. Determine preliminary analysis of anti-tumor activity of this regimen in patients with
recurrent ovarian, fallopian tube or primary peritoneal cancers.
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive carboplatin intravenously (IV) and PLD IV on day 1 and everolimus orally
(PO) once daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence
of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 1 year.
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| Criteria: |
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Inclusion Criteria:
- Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal
carcinoma
- Patients must have had exactly one prior platinum/taxane-based chemotherapeutic
regimen for management of primary disease, and must be in first relapse; first
relapse must occur >= six months from completion of front-line platinum-based
therapy; (time measured from last platinum dose; for example, patients receiving a
biologic or chemotherapeutic agent after completion of platinum-based therapy as part
of upfront therapy would be eligible based on time from last dose of platinum
chemotherapy; in this situation, patients must be at least four weeks from last dose
of a biologic agent); relapse cannot be based on rising cancer antigen (CA)- 125
alone; there must be radiographic evidence of recurrent disease
- Measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
criteria or non-measurable disease with symptomatic malignant pleural effusion or
malignant ascites; if only site of disease is a pleural effusion, cytologic
confirmation of recurrence should be obtained
- Patients must not have any major surgery or radiation therapy within 14 days of start
of study treatment
- All acute toxicities from prior therapy with the exception of alopecia must have
resolved to =< grade 1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Absolute neutrophil count (ANC) >= 1500
- Platelets >= 100K
- Serum total bilirubin =< 1.5x upper limit of normal (ULN)
- Serum transaminase (aspartate aminotransferase [AST]/serum glutamic oxaloacetic
transaminase [SGOT], alanine aminotransferase [ALT]/serum glutamic pyruvic
transaminase [SGPT]) activity =< 2.5 x ULN
- International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) =<
1.5 x ULN for patients who are not being treated with therapeutic anticoagulation;
therapeutic or prophylactic anticoagulation is allowed if a patient has been on a
stable dose of low molecular weight (LMW) heparin for > 2 weeks at the time of
randomization; subjects on therapeutic or prophylactic anticoagulation including
warfarin will have PTT and INR as determined by the Investigator; prophylactic use of
an anticoagulant to maintain patency of a vascular access device is also allowed)
- Serum creatinine =< 2.0
- Creatinine clearance > 60 ml/min
- Left ventricular ejection fraction (LVEF) > lower limit of normal (LLN) on multi
gated acquisition scan (MUGA)
- Ability to understand and willingness to sign a written informed consent document
- Ability to take oral medication
- Fasting serum cholesterol < 300 mg/dL and triglycerides < 2.5 x ULN; Note: in case
one or both of these thresholds are exceeded, the patient can be included after
initiation of appropriate lipid lowering medication if on repeat analysis, both
levels fall within parameters
- Able and willing to comply with testing and treatment as outlined in this protocol
Exclusion Criteria:
- Patients with more than one prior chemotherapy regimen for management of primary
disease
- Patients who have received a prior mammalian target of rapamycin (mTOR) inhibitor
- Chronic treatment with systemic steroids or other immunosuppressive agents; Note:
topical or inhaled steroids are allowed
- Uncontrolled brain or leptomeningeal metastases, including those who continue to
require glucocorticoids for brain or leptomeningeal metastases
- Other malignancies =< 3 years prior to registration except for adequately treated
carcinoma of the cervix or basal or squamous carcinomas of the skin
- Other concurrent severe and/or uncontrolled medical disease which could compromise
participation in the study; examples include, but are not limited to: uncontrolled
diabetes defined as fasting serum glucose > 1.5 x ULN; uncontrolled hypertension, or
greater than 150/100 in spite of antihypertensive therapy; active (acute or chronic)
or uncontrolled severe infection; unstable angina pectoris, symptomatic congestive
heart failure (New York Heart Association Class III or IV); ventricular arrhythmias,
active ischemic heart disease, myocardial infarction within six months; liver disease
such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- Known history of human immunodeficiency virus (HIV) seropositivity as these patients
are at increased risk of lethal infections when treated with marrow-suppressive
therapy and the potential pharmacokinetic interaction between antiretroviral therapy
and the investigational agent
- Known history of Hepatitis B or C as these patients may be at risk of disease
reactivation when treated with the chemotherapy and/or the investigational agent
- Patients should not receive immunization with attenuated live vaccines =< 7 days of
study entry or during study period
- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (i.e. ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection
sufficient to impair absorption of drug)
- Patients with clinical symptoms of gastrointestinal obstruction and who require
parenteral hydration/nutrition
- Patients with an active bleeding diathesis
- Women who are pregnant or breast-feeding, or women able to conceive and unwilling to
practice an effective method of birth control; (women of childbearing potential must
have a negative urine or serum pregnancy test within =< 7 days prior to
administration of RAD001); oral, implantable or injectable contraceptives may be
affected by cytochrome P450 interactions and are therefore not considered effective
for this study
- History of noncompliance with medical regimens
- Patients with a known hypersensitivity to any of the study agents
- Patients unwilling or unable to comply with the outlined protocol
- Patients with psychiatric illness or social situations that would limit compliance
with study requirements
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| NCT ID: |
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NCT01281514 |
| Primary Contact: |
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Principal Investigator
Lainie Martin
Fox Chase Cancer Center
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| Backup Contact: |
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N/A |
| Location Contact: |
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Philadelphia, Pennsylvania 19111
United States
Lainie P. Martin
Phone: 215-728-2814
Email: lainie.martin@fccc.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 20, 2013 |
| Modifications to this listing: |
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