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Advanced CancersPhase 1NCT01183663

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

A Phase 1 study testing Lenalidomide, Bevacizumab and Sorafenib in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Cancers
What is being tested?
Lenalidomide, Bevacizumab and Sorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
1 siteUnited States
Study dates
Aug 2010to May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

The Study Drugs:

Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease or prevent the growth of cancer cells.

Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.

Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.

Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) is a drug combination designed to kill rapidly dividing cells by stopping DNA (the genetic material of cells) from duplicating. Because of a pharmacy shortage of IV leucovorin, patients will continue treatment without leucovorin until it becomes available.

Study Groups (Arms):

If you are found to be eligible to take part in this study, you will be assigned to 1 of 4 study arms. Each study arm will receive lenalidomide in combination with 1 of the 4 drugs/drug combinations described in the "Study Drugs" section above. The arm you are assigned to will depend on what arms are still open and what your doctor thinks is appropriate for you. Your doctor will consider the type of disease you have, other drugs you have received for the disease, and any side effects you may have seen with other drugs when deciding which arm you should be assigned to:

  • If you are in Arm 1, you will receive lenalidomide and bevacizumab.
  • If you are in Arm 2, you will receive lenalidomide and sorafenib.
  • If you are in Arm 3, you will receive lenalidomide and temsirolimus.
  • If you are in Arm 4, you will receive lenalidomide and FOLFOX.

Up to 4 dose levels of the drug combination will be tested for each arm. Up to 6 participants will be enrolled at each dose level in each arm. For each arm, the first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose for the drug combination is found for each arm. After the highest tolerable dose of the drug combination is found, an additional 20 patients will be able to receive this combination dose in each arm.

Study Drug Administration:

If you are in Arm 1, 2, or 3, each study "cycle" will be 28 days. If you are in Arm 4, each study cycle will be 21 days.

If you are in Arms 1, 2, or 3, you will take lenalidomide by mouth 1 time each day during Days 1-21 of each study cycle. If you are in Arm 4, you will take lenalidomide by mouth 1 time each day during Days 1-14 of each study cycle. Swallow lenalidomide capsules whole with 1 cup (about 8 ounces) of water. Do not break, chew, or open the capsules.

If you miss a dose of lenalidomide, take is as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact the study staff right away. Women who are able to become pregnant that might be caring for you should not touch the lenalidomide capsules or bottles unless they are wearing gloves. Any unused Revlimid® (lenalidomide) should be returned as instructed through the RevAssist® program.

Arm 1:

You will receive bevacizumab by vein on Days 1 and 15 of each cycle. The first time you receive bevacizumab, it will be given over 90 minutes. If you tolerate it well, the rest of the doses will be given over 30-60 minutes.

Arm 2:

You will take sorafenib by mouth 1 time each day of every cycle (Days 1-28). You should take it with a cup (8 ounces) of water, after taking lenalidomide. You should not eat or drink anything other than water for at least 1 hour before or after taking sorafenib.

Arm 3:

You will receive temsirolimus by vein over 30-60 minutes on Days 1, 8, 15, and 22 of each cycle.

Arm 4:

You will receive oxaliplatin and leucovorin by vein over 2 hours on Day 1 of each cycle. You will also receive 5-FU by vein over 22 hours at home on Days 1-2. The drug will be given through a pump that you carry with you.

Study Visits:

At all study visits, you will be asked about any side effects you may be having and about any other drugs you may be receiving.

On Day 1 of Cycle 1, the following tests and procedures will be performed if they were not performed within 7 days before Day 1 of Cycle 1:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

On Day 15 of Cycle 1, blood (about 1 tablespoon ) will be drawn for routine tests.

On Day 1 of every even numbered cycle (Cycles 2, 4, 6, and so on):

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

At the end of every even numbered cycle (Day 28 for Arms 1, 2, and 3; Day 21 for Arm 4):

  • You will have a CT scan, MRI scan, positron emission computed tomograph (PET) scan, or a PET/CT scan to check the status of the disease. If the study doctor thinks it is in your best interest, other types of scans that have not been listed here may also be performed. The study doctor will explain these other types of scans to you in more detail, and you may be asked to sign a separate consent form that describes the scans and their risks in more detail.
  • If your study doctor thinks it is needed, you will have either a CT or MRI scan of the brain to check the status of the disease.
  • Blood (about 1 tablespoon) will be drawn for tumor markers.

On Day 1 of every odd numbered cycle (Cycles 3, 5, 7, and so on):

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

Pregnancy Testing:

If you are a woman who is able to become pregnant, you will have blood (about 1 teaspoon) or urine pregnancy tests on Day 1 of every cycle, 1 time each week during the first cycle, when you stop taking the study drugs, and 30 days after you stop taking the study drugs.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Follow-Up Visit:

Thirty (30) days after you stop taking the study drugs for any reason, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 2 tablespoons) will be drawn for routine tests and tumor marker testing.
  • You will have an ECG.
  • You will have a CT scan, MRI scan, PET scan, or PET/CT scan to check the status of the disease. If the study doctor thinks it is in your best interest, other types of scans that have not been listed here may also be performed. The study doctor will explain these other types of scans to you in more detail, and you may be asked to sign a separate consent form that describes the scans and their risks in more detail.
  • If your study doctor thinks it is needed, you will have either a CT or MRI scan of the brain to check the status of the disease.

This is an investigational study. All of the study drugs are FDA-approved and commercially available for use in various types of cancer:

  • Lenalidomide: multiple myeloma and myelodysplastic syndrome
  • Bevacizumab: colorectal and lung cancers
  • Sorafenib: liver carcinoma and renal cell carcinoma
  • Temsirolimus: renal cell carcinoma
  • 5-FU: cancers of the breast, pancreas, colon/rectum, stomach, and a type of skin cancer (superficial basal cell carcinoma)
  • Oxaliplatin and leucovorin: colorectal cancer

It is investigational to give lenalidomide in combination with each of the other drugs to patients with advanced cancer.

Up to 180 participants will take part in this study. All will be enrolled at MD Anderson.

Being tested
Lenalidomide, Bevacizumab, Sorafenib, Temsirolimus, Oxaliplatin
Keywords
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
Medical subject headings
Neoplasm Metastasis, Colorectal Neoplasms, Hematologic Neoplasms, Colonic Neoplasms, Breast Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenalidomideDrug

    Also called CC-5013, Revlimid

    Starting dose 10 mg by mouth daily for 21 days of a 28 day cycle.

  • BevacizumabDrug

    Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAB-VEGF

    Starting dose: 5 mg/kg by vein every 2 weeks of a 28 day cycle.

  • SorafenibDrug

    Also called Nexavar, BAY 43-90006

    Starting dose: 200 mg by mouth daily for 28 a day cycle.

  • TemsirolimusDrug

    Also called CC-779, Torisel

    Starting dose: 15 mg by vein every week for a 28 day cycle.

  • LenalidomideDrug

    Also called CC-5013, Revlimid

    Starting dose: 5 mg by mouth daily for 14 days of a 21 day cycle.

  • OxaliplatinDrug

    Also called Eloxatin

    Starting dose: 65 mg/m2 by vein on day 1 of a 21 day cycle.

  • LeucovorinDrug

    Also called Citrovorum, Wellcovorin

    400 mg/m2 by vein on day 1 of a 21 day cycle.

  • 5-fluorouracilDrug

    Also called 5-FU, Adrucil, Efudex

    400 mg/m2 by vein through ambulatory pump on days 1-2 of a 21 day cycle.

Study groups in NCT01183663
Study groupRoleWhat they receive
Lenalidomide + BevacizumabExperimentalLenalidomide 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.
Receives: Drug: Lenalidomide; Drug: Bevacizumab
Lenalidomide + SorafenibExperimentalLenalidomide 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.
Receives: Drug: Lenalidomide; Drug: Sorafenib
Lenalidomide + TemsirolimusExperimentalLenalidomide 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.
Receives: Drug: Lenalidomide; Drug: Temsirolimus
Lenalidomide + Oxaliplatin + Leucovorin + 5-fluorouracilExperimentalLenalidomide 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.
Receives: Drug: Lenalidomide; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: First 21/28 day cycle

Secondary outcomes (1)

  1. Tumor Response

    Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e., decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionMay 2016
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01183663
Sponsor's protocol ID
2010-0108
Other IDs
NCI-2012-01790
Status last verified
Jun 2016
First submitted
13 Aug 2010
Last updated
3 Jun 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 23756764

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lenalidomide, Bevacizumab and Sorafenib in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01183663, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2016.

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