- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00967928
Everolimus Dose Finding Study for Stage IV or Recurrent Cervical Cancer
February 13, 2014 updated by: Accelerated Community Oncology Research Network
Phase I Everolimus Dose Finding Study for the Treatment of Stage IV or Recurrent, Non-resectable, Cervical Cancer With Standard Whole Pelvic Radiation Therapy in Combination With Weekly Cisplatin and Daily Everolimus
This Phase 1, single-site, dose-escalation study is being conducted to determine the maximum tolerated dose (MTD) of RAD001 as part of a specified combination regimen.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
This Phase 1, single-site, dose-escalation study is being conducted to determine the MTD of RAD001 as part of a specified combination regimen.
The combination regimen will be standard field whole pelvic RT in combination with cisplatin at 40mg/m2 weekly with RAD001 at dose escalation daily starting at 5 mg qod, then 5 mg qd, then 10 mg qd during the period of whole pelvic radiation therapy.
Study Type
Interventional
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors criteria that has not been previously irradiated.
- Female patient aged ≥18 years.
- Patient has life expectancy of at least 12 weeks at study start.
- Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study start.
- Patient has diagnosis of stage IV or recurrent, non-resectable, cervical cancer at study start.
- Patient has received no prior chemotherapy.
Patient has adequate hematologic function:
- Absolute neutrophil count [ANC] ≥1500/μL
- Platelets ≥100,000/μL
- Hemoglobin > 9g/dL
Patient has adequate renal function:
- Serum creatinine ≤ 2.0 mg/dL
- Calculated creatinine clearance ≥ 50 mL/min
Patient has adequate hepatic function:
- Serum bilirubin ≤1.5 x ULN
- ALT and AST ≤2.5 × ULN (≤ 5 x ULN in patients with liver metastases)
- INR <1.5 (or < 3 on anticoagulants)
- Patient has fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN.
- Patient is able to provide signed informed consent.
Exclusion Criteria:
- Patient has neuroendocrine or small cell carcinoma of the cervix.
- Patient has previously used any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.
- Patient is currently receiving anticancer therapies or has received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.).
- Patient has had a major surgery or significant traumatic injury within 4 weeks of start of study drug; patient has not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patient might require major surgery during the course of the study.
- Patient has had prior treatment with any investigational drug within the preceding 4 weeks before study start.
- Patient is receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Patients should also avoid close contact with people who have received live vaccines during treatment with everolimus. Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, and TY21a typhoid vaccines.
- Patient has known brain or leptomeningeal metastases.
- Patient has had other malignancies within the past 3 years except for adequately treated squamous cell carcinomas of the skin.
Patients has any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York Heart Association Class III or IV.
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
- Severely impaired lung function defined as spirometry and diffusing capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.
- Uncontrolled diabetes as defined by fasting serum glucose >1.5 × ULN.
- Active (acute or chronic) or uncontrolled severe infections.
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
- Patient has a known history of human immunodeficiency virus seropositivity.
- Patient has impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- Patient has an active, bleeding diathesis.
- Female patient who is pregnant or breast feeding, or an adult of reproductive potential who is not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial and for up to 8 weeks after ending treatment by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001.)
- Patient has received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
- Patient has a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Patient has history of noncompliance to medical regimens.
- Patient is unwilling to or unable to comply with the protocol.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single arm
All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.
|
RAD001 will be administered orally as 5 mg qod, 5 mg qd, or 10mg qd continuously from study Day 1 until the end of whole pelvic radiation therapy unless the patient develops progression of disease or unacceptable toxicity prior to that.
Other Names:
Cisplatin will be administered intravenously once weekly at 40mg/m2 for 6 weeks.
The preferred administration day is Monday.
Other Names:
Patients will receive 180 cGy daily fraction Monday through Friday x 25 days (4500 cGy total) using a four field technique throughout the entire treatment with all fields treated each day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the maximum tolerated dose for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
Time Frame: every 7 days
|
every 7 days
|
To determine the dose limiting toxicities for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
Time Frame: every 7 days
|
every 7 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the pharmacokinetics of RAD001 given as adjunct therapy to standard upfront treatment of advanced stage cervical cancer
Time Frame: day 1 and day 15 during study treatment
|
day 1 and day 15 during study treatment
|
To evaluate the pharmacogenetics of RAD001 in the specified patient population
Time Frame: day 1 prior to starting study treatment
|
day 1 prior to starting study treatment
|
To evaluate microvessel density pre-and post-treatment with the specified treatment regimen in the specified patient population
Time Frame: day 1 and end of treatment
|
day 1 and end of treatment
|
To evaluate potential correlations between biomarkers HIF-1a, TSP-1, P53, VEGF, and VEGFR and use of the specified treatment regimen in the specified patient population
Time Frame: day 1 and end of treatment
|
day 1 and end of treatment
|
To evaluate progression free survival in the specified patient population
Time Frame: from the time of treatment start until progression or up to 5 years after completion of study treatment
|
from the time of treatment start until progression or up to 5 years after completion of study treatment
|
To assess quality of life as indicated by the Patient Care Monitor in the specified patient population
Time Frame: every 7 days during study treatment
|
every 7 days during study treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2009
Primary Completion (Anticipated)
December 1, 2010
Study Completion (Anticipated)
December 1, 2010
Study Registration Dates
First Submitted
August 27, 2009
First Submitted That Met QC Criteria
August 27, 2009
First Posted (Estimate)
August 28, 2009
Study Record Updates
Last Update Posted (Estimate)
February 14, 2014
Last Update Submitted That Met QC Criteria
February 13, 2014
Last Verified
February 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ATDTCC0801
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
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Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
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National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
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Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
-
Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
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