Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)
A Phase I Study of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) in Patients With Advanced Cancers
2 other identifiers
interventional
180
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable doses of the combinations of lenalidomide and other drugs that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2010
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2010
CompletedFirst Submitted
Initial submission to the registry
August 13, 2010
CompletedFirst Posted
Study publicly available on registry
August 17, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedJune 3, 2016
June 1, 2016
5.8 years
August 13, 2010
June 1, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)
If more than 33% of patients enrolled in any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of patients in cohort develop DLT, this cohort considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity, as defined in most current version of NCI CTCAE, even if expected and believed related to study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens, or alopecia), any Grade 4 hematologic toxicity lasting at least 7 days or longer, despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting lasting \> 5 days despite maximum anti-nausea regimens and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in NCI CTCAE.
First 21/28 day cycle
Secondary Outcomes (1)
Tumor Response
4 months
Study Arms (4)
Lenalidomide + Bevacizumab
EXPERIMENTALLenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Bevacizumab starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.
Lenalidomide + Sorafenib
EXPERIMENTALLenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Sorafenib starting dose: 200 mg by mouth daily for 28 a day cycle.
Lenalidomide + Temsirolimus
EXPERIMENTALLenalidomide starting dose: 10 mg by mouth daily for 21 days of a 28 day cycle. Temsirolimus starting dose: 15 mg by vein every week for a 28 day cycle.
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
EXPERIMENTALLenalidomide starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle. Oxaliplatin starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle. Leucovorin 400 mg/m2 by vein on day 1 of a 21 day cycle. 5-fluorouracil 400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
Interventions
Starting dose 10 mg by mouth daily for 21 days of a 28 day cycle.
Starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.
Starting dose: 200 mg by mouth daily for 28 a day cycle.
Starting dose: 15 mg by vein every week for a 28 day cycle.
Starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle.
400 mg/m2 by vein on day 1 of a 21 day cycle.
400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
Eligibility Criteria
You may qualify if:
- Patients with advanced or metastatic cancer that is refractory to standard therapy, has relapsed after standard therapy, or for which there is no standard therapy available.
- Patients must be \>/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, therapeutic radiation, or major surgery. After targeted or biologic therapy there should be 5 half-lives or three weeks, whichever is shorter. Patients may have received palliative localized radiation immediately before or during treatment, providing radiation is not delivered only to the site of disease being treated under this protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status \</= 2
- Patients must have normal organ and marrow function, defined as absolute neutrophil count \>/= 1,000/mL; platelets \>/=50,000/mL (unless these abnormalities are due to bone marrow involvement); creatinine clearance \>/= 50 ml/min by Cockcroft-Gault formula; total bilirubin \</= 2.0; and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase(SGPT) \</= 5 X upper limit of normal (ULN) (unless patient has liver metastases).
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International unit (mIU)/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- Patients must be able to understand and be willing to sign a written informed consent document.
- Must be \>/= 18 years of age.
You may not qualify if:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Use of any other experimental drug or therapy within 21 days of baseline.
- Known hypersensitivity to thalidomide.
- History of hypersensitivity to any component of the formulation.
- The development of erythema nodosum, if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Patients unwilling or unable to sign informed consent document.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure \>140 mmHg, diastolic blood pressure \> 90 mmHg on medication) for patients treated in the bevacizumab or sorafenib arms.
- Patients with active deep venous thrombosis or pulmonary embolism or patients receiving anti-coagulation.
- Patients with clinically significant cardiovascular disease: History of cerebro-vascular accident (CVA) within 6 months; Myocardial infarction or unstable angina within 6 months; Unstable angina pectoris.
- Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 of protocol treatment.
- Patients that are taking CYP3A4 inducers and/or inhibitors, being considered for the temsirolimus arm: If a patient has a history of taking CYP3A4 inducers and/or inhibitors prior to enrollment on the temsirolimus arm, it is strongly recommended that the patient stops the drug and waits at least 5 half-lives of said drug before initiating therapy on the temsirolimus arm.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Celgenecollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Ganesan P, Piha-Paul S, Naing A, Falchook G, Wheler J, Fu S, Hong DS, Kurzrock R, Janku F, Laday S, Bedikian AY, Kies M, Wolff RA, Tsimberidou AM. Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer. Invest New Drugs. 2014 Apr;32(2):279-86. doi: 10.1007/s10637-013-9966-3. Epub 2013 Jun 12.
PMID: 23756764DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Apostolia M. Tsimberidou, MD, PhD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 13, 2010
First Posted
August 17, 2010
Study Start
August 1, 2010
Primary Completion
May 1, 2016
Study Completion
May 1, 2016
Last Updated
June 3, 2016
Record last verified: 2016-06