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Recurrent Colon CarcinomaPhase 1NCT01383343

Sorafenib Tosylate, Bevacizumab, Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer

A Phase 1 study testing Bevacizumab, Fluorouracil and Irinotecan Hydrochloride in people with Recurrent Colon Carcinoma and Recurrent Rectal Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

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

Official record
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Trial summary

This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with bevacizumab, irinotecan hydrochloride, leucovorin calcium, and fluorouracil in treating patients with colorectal cancer that has spread to other parts of the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Fluorouracil and Irinotecan Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
3 sitesUnited States
Study dates
Aug 2011to Feb 2017
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

  • This trial is intended for gastrointestinal malignancies appropriate for irinotecan-based therapy; histologic proof of cancer that is now unresectable; if prior therapy was received, patients must have shown progressive disease during prior treatment or within 6 months of their most recent therapy
  • Measurable disease or non-measurable disease
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet (PLT) >= 100,000/uL
  • Hemoglobin (Hgb) >= 9.0 gm/dL
  • Total bilirubin =< upper limit of normal (ULN)
Show all 18Show fewer
  • Alkaline phosphatase =< 3 x ULN
  • Aspartate aminotransferase (AST) =< 3 x ULN OR AST =< 5 x ULN if liver involvement
  • International normalized ratio (INR) < 1.5 unless patients are receiving anti-coagulation therapy; patients receiving anti-coagulation therapy with an agent such as warfarin or heparin are allowed to participate if INR =< 3.0
  • Urine protein creatinine (UPC) ratio < 1 or urine dipstick < 2+
  • NOTE: urine protein must be screened by urine analysis for UPC ratio or by dipstick; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1000 mg
  • Creatinine =< 1.5 x ULN
  • Calculated creatinine clearance must be >= 45 mL/min using the Cockcroft-Gault formula
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Ability to provide informed consent
  • Willing to return to Mayo Clinic for follow up
  • Life expectancy >= 84 days (3 months)
  • Women of childbearing potential only: negative pregnancy test done =< 7 days prior to registration

Who cannot join

  • Known standard therapy for patient's disease that is potentially curative
  • Note:
  • Prior treatment with irinotecan, 5-fluoruracil or bevacizumab is allowed
  • Prior treatment with sorafenib is not allowed
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
Show all 35Show fewer
  • History of myocardial infarction or unstable angina =< 6 months prior to registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Heart failure New York Heart Association classification III or IV
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks =< 6 months prior to registration
  • Any hemorrhage/bleeding event > grade 3 =< 4 weeks prior to registration
  • Evidence or history of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation); NOTE: patients on full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin or warfarin and has an INR in the range of 2-3; aspirin doses > 325 mg PO daily are not allowed
  • Active or recent hemoptysis (>= ½ teaspoon of bright red blood per episode) =< 30 days prior to registration
  • Serious, non-healing wound, active ulcer, or untreated bone fracture; NOTE: patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection), recent peripheral arterial thrombosis, symptomatic peripheral vascular disease =< 6 months prior to registration
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
  • Major surgical procedures, open biopsy, or significant traumatic injury =< 28 days prior to registration or anticipation of need for major surgical procedure during the course of the study; EXCEPTION: core biopsy or minor surgical procedure, including placement of a vascular access device, =< 7 days prior to registration is allowed
  • Patients taking cytochrome P450 enzyme-inducing antiepileptic drugs =< 4 weeks prior to registration will be excluded (phenytoin, carbamazepine, phenobarbital, rifampin, or St. John's wort)
  • Known or suspected allergy or hypersensitivity to any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Any of the following prior therapies:
  • Chemotherapy =< 14 days prior to registration
  • Immunotherapy =< 28 days prior to registration
  • Radiation therapy =< 28 days prior to registration
  • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • Known brain metastasis; NOTE: patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer, including hormonal therapy

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase I Trial of FOLFIRI in Combination With Sorafenib and Bevacizumab in Patients With Advanced Gastrointestinal Malignancies

This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with bevacizumab, irinotecan hydrochloride, leucovorin calcium, and fluorouracil in treating patients with colorectal cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Sorafenib tosylate and bevacizumab may also block tumor growth in different ways by targeting certain cells. Giving sorafenib tosylate and bevacizumab together with combination chemotherapy may be a better treatment for colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose of the combination of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) plus sorafenib (sorafenib tosylate) plus bevacizumab.

SECONDARY OBJECTIVES:

  1. To assess the safety of FOLFIRI plus sorafenib plus bevacizumab. II. To assess the feasibility of the proposed combination. III. To evaluate the response rate and identify any activity of the proposed combination.

OUTLINE: This is a dose-escalation study of sorafenib tosylate followed by a cohort study. (Cohort study cancelled as of March 25, 2014)

Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, fluorouracil IV continuously over 46 hours on days 1-2, bevacizumab IV over 30-90 minutes on day 1, and sorafenib tosylate orally (PO) once (QD) or twice daily (BID) on days 3-6 and 10-13*. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may also receive sorafenib tosylate on days 7 and 14.

After completion of study therapy, patients are followed up for 3 months.

Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • FluorouracilDrug

    Also called 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • Irinotecan HydrochlorideDrug

    Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

    Given PO

Study groups in NCT01383343
Study groupRoleWhat they receive
Treatment (FOLFIRI and bevacizumab)ExperimentalPatients receive irinotecan hydrochloride IV over 90 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, fluorouracil IV continuously over 46 hours on days 1-2, bevacizumab IV over 30-90 minutes on day 1, and sorafenib tosylate PO QD or BID on days 3-6 and 10-13*. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Sorafenib Tosylate

What is being measured

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

  1. Maximum tolerated dose of sorafenib tosylate in combination with FOLFIRI and bevacizumab, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients)

    Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 14 days

Secondary outcomes (7)

  1. Incidence of adverse events of sorafenib tosylate in combination with bevacizumab and FOLFIRI as assessed by NCI CTCAE v 4.0

    The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 3 months

  2. Response rate in patients treated with sorafenib tosylate in combination with FOLFIRI and bevacizumab, assessed using Response Evaluation Criteria in Solid Tumors

    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

    Measured: From the start of the treatment until disease progression/recurrence, assessed up to 3 months

  3. Time to progression

    Measured: Up to 3 months

  4. Time to treatment failure

    Measured: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months

  5. Time to until treatment related grade 3+ toxicity assessed via CTC standard toxicity grading

    Will be assessed using continuous variables as the outcome measures (primarily nadir). Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 3 months

  6. Time until any treatment related toxicity evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading

    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 3 months

  7. Time until hematologic nadirs (ANC, platelets, hemoglobin)

    Descriptive statistics and simple scatter plots will form the basis of presentation of these data.

    Measured: Up to 3 months

Timeline

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

  1. First posted28 Jun 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionFeb 2017
  4. Study completionFeb 2017

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01383343
Sponsor's protocol ID
NCI-2011-02595
Other IDs
NCI-2011-02595, CDR0000702751, MC1017, MC1017, 8877, P30CA015083, U01CA069912, UM1CA186686
Status last verified
Apr 2017
First submitted
25 Jun 2011
Last updated
19 Apr 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Fluorouracil and Irinotecan Hydrochloride in people with Recurrent Colon Carcinoma and Recurrent Rectal Carcinoma, run by National Cancer Institute (NCI) at 3 sites 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 18 inclusion and 35 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 19 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 of sorafenib tosylate in combination with FOLFIRI and bevacizumab, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (time frame: 14 days). 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 NCT01383343.

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 19 Apr 2017.

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