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Recurrent Colon CancerPhase 1NCT01238965

Panobinostat and Fluorouracil Followed By Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer Who Did Not Respond to Previous Fluorouracil-Based Chemotherapy

A Phase 1 study testing panobinostat, fluorouracil and leucovorin calcium in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by University of Southern California at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
panobinostat, fluorouracil and leucovorin calcium
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
Oct 2010to Apr 2015
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 must have histologically or cytologically confirmed advanced/metastatic colorectal cancer
  • Must have measurable disease
  • Must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin; (may have received prior erbitux and bevacizumab, but it is not required)
  • Must have received at least one prior chemotherapy regimen for advanced disease
  • Tumor must be accessible for core biopsy at the beginning of treatment and patients have a high intratumoral TS expression level prior to the beginning of treatment
  • Life expectancy of > 12 weeks
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  • ECOG performance status 0-2 (Karnofsky >= 50%)
  • Normal organ and marrow function as defined below:
  • Serum albumin >= 3g/dL
  • AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal(ULN)or =< 5.0 x ULN if the transaminase elevation is due to liver metastasis
  • Serum bilirubin =< 1.5 x ULN
  • Serum creatinine =< 1.5 x ULN or 24-hr creatinine clearance >= 50 ml/min
  • Serum potassium >= LLN
  • Serum phosphorous >= LLN
  • Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN
  • Serum magnesium >= LLN
  • TSH and free T4 within normal limits(WNL)(patients may be on thyroid hormone replacement)
  • Leukocytes >= 3,000/μL
  • Absolute neutrophil count >= 1,500/μL
  • Platelets >= 100,000/μL
  • Hemoglobin >= 9 mg/dL
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of LBH589 will be determined following review by the Principal Investigator
  • Ability to understand and willing to sign a written informed consent document
  • INR is =< 1.5 times ULN unless receiving therapeutic anticoagulation
  • Patient is highly unlikely to conceive as indicated by at least one "yes" answer to the following questions:
  • patient is a male and agrees to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication;
  • surgically sterilized female;
  • postmenopausal female >= 45 years of age with > 2 years since last menses;
  • non-sterilized premenopausal female and agrees to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study and for 30 days after the last dose of study medication
  • Baseline MUGA must demonstrate LVEF >= the lower limit of the institutional normal
  • Clinically euthyroid; Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism

Who cannot join

  • Male patients whose sexual partners are WOCBP not using effective birth control
  • May not have received any other investigational agents within 28 days of study entry (chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy).
  • May not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
  • Patients with known brain metastases are excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to LBH589; including sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide
  • Severe and/or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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  • Pregnant or breast feeding or patients of reproductive potential not using two effective methods of birth control; women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
  • History of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
  • Unresolved diarrhea > CTCAE grade 1
  • Acute infection requiring intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drugs
  • Known positivity for human immunodeficiency virus (HIV) or hepatitis C
  • Screening ECG with a QTc > 450 msec
  • Patients with congenital long QT syndrome
  • History of sustained ventricular tachycardia
  • Any history of ventricular fibrillation or torsades de pointes
  • Bradycardia defined as heart rate < 50 beats per minute; patients with a pacemaker and heart rate >= 50 beats per minute are eligible
  • Myocardial infarction or unstable angina within 6 months of study entry
  • Congestive heart failure (NY Heart Association class III or IV)
  • Right bundle branch block and left anterior hemiblock (bifascicular block)
  • Prior cancer treatment with an HDAC inhibitor (e.g., vorinostat, Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid)
  • Uncontrolled hypertension
  • Concomitant use of drugs with a risk of causing torsades de pointes
  • Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
  • Patients needing valproic acid for any medical condition during the study or within 5 days prior to first LBH589

Trial locations and contacts

1 site in 1 country.

United States1 site

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: Phase I Clinical Trial With LBH589 and Infusional 5-FU/LV in Patients With Metastatic Colorectal Cancer Who Failed 5-FU Based Chemotherapy

Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with fluorouracil and leucovorin calcium may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and the best dose of giving panobinostat, fluorouracil, and leucovorin calcium together in treating patients with stage IV colorectal cancer who did not respond to previous fluorouracil-based chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and feasibility of combining LBH589 with infusional 5-FU chemotherapy in the treatment of Stage IV colorectal cancer patients who have progressed on standard 5-FU regimens.

II. To determine the efficacy of LBH589 alone to produce consistent decreases in tumor thymidylate synthase (TS) expression.

SECONDARY OBJECTIVES:

  1. To determine the time to tumor progression, progression free and overall survival of patients with advanced or metastatic colorectal cancer treated with LBH589 combined with infusional 5-FU.

II. To determine if TS repression by LBH589 predicts response to the combination of LBH589 and infusional 5-FU in patients who have already progressed on standard regimens containing 5-FU.

III. To obtain preliminary data on gene expression levels of TS, DPD and TP as well as germline polymorphisms of TS being associated with clinical outcome and toxicity.

IV. To obtain preliminary data on acetylation on peripheral blood mononuclear cells to establish biological activity in these patients at time of biopsies.

OUTLINE: Patients receive oral panobinostat 3 times a week. Patients also receive leucovorin calcium IV over 2 hours on days 1 and 15 followed by fluorouracil IV continuously over 46 hours on days 1-2 and 15-16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Being tested
panobinostat, fluorouracil, leucovorin calcium, biopsy, reverse transcriptase-polymerase chain reaction
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.

  • panobinostatDrug

    Also called Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

    Given orally

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil

    Given IV

  • leucovorin calciumDrug

    Also called calcium folinate, CF, CFR, citrovorum factor

    Given IV

  • biopsyProcedure or surgery

    Also called biopsies

    Correlative studies

  • reverse transcriptase-polymerase chain reactionGenetic

    Also called RT-PCR

    Correlative studies

  • western blottingGenetic

    Also called Blotting, Western, Western Blot

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

  • gene expression analysisGenetic

    Correlative studies

  • RNA analysisGenetic

    Correlative studies

  • polymorphism analysisGenetic

    Correlative studies

Study groups in NCT01238965
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral panobinostat 3 times a week. Patients also receive leucovorin calcium IV over 2 hours on days 1 and 15 followed by fluorouracil IV continuously over 46 hours on days 1-2 and 15-16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: panobinostat; Drug: fluorouracil; Drug: leucovorin calcium; Procedure: biopsy; Genetic: reverse transcriptase-polymerase chain reaction; Genetic: western blotting; Other: laboratory biomarker analysis; Genetic: gene expression analysis; Genetic: RNA analysis; Genetic: polymorphism analysis

What is being measured

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

  1. To assess the safety of this regimen

    Measured: Up to 12 months

Secondary outcomes (3)

  1. Time to progression

    Measured: At 3, 6, 9, and 12 months

  2. Overall response rate

    Measured: Every 2 months until disease recurrence or progression

  3. Overall survival

    Measured: At 3, 6, 9, and 12 months

Timeline

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

  1. First posted11 Nov 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionDec 2014
  4. Study completionApr 2015

Why it stopped: Adverse Events

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
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01238965
Sponsor's protocol ID
3C-08-1
Other IDs
NCI-2010-02149
Status last verified
May 2015
First submitted
3 Nov 2010
Last updated
27 May 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing panobinostat, fluorouracil and leucovorin calcium in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by University of Southern California 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 31 inclusion and 25 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: stopped early, as of the sponsor's last update on 27 May 2015. 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 was stopped early (reason given: Adverse Events). Results are not available in the source record.

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?

To assess the safety of this regimen (time frame: Up to 12 months). 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 NCT01238965.

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 27 May 2015.

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