Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01183663
First received: August 13, 2010
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Drug: Lenalidomide
Drug: Bevacizumab
Drug: Sorafenib
Drug: Temsirolimus
Drug: Oxaliplatin
Drug: Leucovorin
Drug: 5-fluorouracil
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) in Patients With Advanced Cancers

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) [ Time Frame: First 21/28 day cycle ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 180
Study Start Date: August 2010
Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide + Bevacizumab
Lenalidomide 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.
Drug: Lenalidomide
Starting dose 10 mg by mouth daily for 21 days of a 28 day cycle.
Other Names:
  • CC-5013
  • Revlimid
Drug: Bevacizumab
Starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAB-VEGF
Experimental: Lenalidomide + Sorafenib
Lenalidomide 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.
Drug: Lenalidomide
Starting dose 10 mg by mouth daily for 21 days of a 28 day cycle.
Other Names:
  • CC-5013
  • Revlimid
Drug: Sorafenib
Starting dose: 200 mg by mouth daily for 28 a day cycle.
Other Names:
  • Nexavar
  • BAY 43-90006
Experimental: Lenalidomide + Temsirolimus
Lenalidomide 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.
Drug: Lenalidomide
Starting dose 10 mg by mouth daily for 21 days of a 28 day cycle.
Other Names:
  • CC-5013
  • Revlimid
Drug: Temsirolimus
Starting dose: 15 mg by vein every week for a 28 day cycle.
Other Names:
  • CC-779
  • Torisel
Experimental: Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracil
Lenalidomide 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.
Drug: Lenalidomide
Starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle.
Other Names:
  • CC-5013
  • Revlimid
Drug: Oxaliplatin
Starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle.
Other Name: Eloxatin
Drug: Leucovorin
400 mg/m2 by vein on day 1 of a 21 day cycle.
Other Names:
  • Citrovorum
  • Wellcovorin
Drug: 5-fluorouracil
400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.
Other Names:
  • 5-FU
  • Adrucil
  • Efudex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Eastern Cooperative Oncology Group (ECOG) performance status </= 2
  4. 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 ULN (unless patient has liver metastases).
  5. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  6. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 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.
  7. Patients must be able to understand and be willing to sign a written informed consent document.
  8. Must be >/= 18 years of age.

Exclusion Criteria:

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  2. Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
  3. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  4. Use of any other experimental drug or therapy within 21 days of baseline.
  5. Known hypersensitivity to thalidomide.
  6. History of hypersensitivity to any component of the formulation.
  7. The development of erythema nodosum, if characterized by a desquamating rash while taking thalidomide or similar drugs.
  8. Patients unwilling or unable to sign informed consent document.
  9. 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.
  10. Patients with active deep venous thrombosis or pulmonary embolism or patients receiving anti-coagulation.
  11. 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.
  12. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
  13. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 of protocol treatment.
  14. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183663

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Apostolia M. Tsimberidou, MD, PhD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01183663     History of Changes
Other Study ID Numbers: 2010-0108, NCI-2012-01790
Study First Received: August 13, 2010
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Lenalidomide
Bevacizumab
Sorafenib
Temsirolimus
5-Fluorouracil
Leucovorin
Oxaliplatin
Avastin
Anti-VEGF monoclonal antibody
rhuMAB-VEGF
CC-5013
Revlimid
Nexavar
BAY 43-90006
Metastatic cancer
Metastatic colorectal cancer
Advanced solid tumors
Hematologic malignancies
Colon cancer
Advanced colorectal cancer
Breast cancer
Pancreatic cancer
Gastric cancer
Advanced renal cell carcinoma
Prostate cancer
Melanoma
Unresectable hepatocellular carcinoma
Renal cell carcinoma
Metastatic breast cancer
Glioblastoma

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Bevacizumab
Everolimus
Fluorouracil
Lenalidomide
Oxaliplatin
Sirolimus
Sorafenib
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014