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MucositisPhase 1NCT01728480

Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

A Phase 1 study testing entolimod, intensity-modulated radiation therapy and cisplatin in people with Mucositis and Recurrent Squamous Cell Carcinoma of the Hypopharynx, run by Roswell Park Cancer Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of entolimod in treating patients with stage III-IV or recurrent head and neck cancer. Biological therapies, such as entolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
entolimod, intensity-modulated radiation therapy and cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2014to Oct 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

  • Histologically proven diagnosis of squamous cell carcinoma (stage III - IV) of the nasopharynx, oropharynx, oral cavity, paranasal sinuses, larynx, hypopharynx; the tumor must be human papillomavirus (HPV) negative or the patient should have a greater than 10 packs year smoking history; OR need for post-operative concurrent chemoradiotherapy (extracapsular extension, positive surgical margin, more than 1 lymph node positive, stage III - IV disease, perineural invasion, vascular tumor embolus) for histologically proven squamous cell carcinoma of the paranasal sinuses, nasopharynx, larynx, hypopharynx, with extension to structures of the oropharynx
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Induction chemotherapy (up to 3 cycles of cetuximab/taxanes/platinum based regimens) is allowed
  • Patients or their legal representatives must be able to comprehend and provide written informed consent
  • Absolute neutrophil count => 1,500/uL
  • Platelets >= 100,000/uL
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  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit normal (ULN)
  • Calculated creatinine clearance >= 60 mL/min (Cockcroft-Gault equation)
  • 12-Lead Electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
  • Bazett's corrected QT (QTcB) interval < 470 msec at any timepoint prior to receiving the first dose of study drug (mean of replicate values, correction per institutional standard) and no history of Torsades des Pointes or other symptomatic QTcB abnormality
  • Absence of orthostatic hypotension
  • Patients must be sufficiently recovered from induction chemotherapy to allow initiation therapy

Who cannot join

  • Women of childbearing potential who do not have a negative serum pregnancy test performed within 7 days prior to the start of study drug
  • Male and female patients of child-bearing potential who do not agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
  • Contraindication to full course chemoradiotherapy with cisplatin
  • Previous treatment with a toll-like receptor 5 (TLR5) agonist
  • Presence of neutralizing antibodies to CBLB502
  • Patients with an active infection or with a fever >= 38.5ºC within 3 days of the first scheduled day of dosing; patients who are registered but develop a fever of >= 38.5ºC may remain in the study if the fever abates prior to the expiration of the screening procedures; if the screening procedures have expired, the patient may be re-screened once afebrile
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  • Patients with a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory or inflammatory illness that could preclude their participation in the study, pose an undue medical hazard or interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (New York Heart Association [NYHA] class 3 or class 4); unstable angina; cardiac arrhythmia; recent (within the preceding 6 months) myocardial infarction or stroke; hypertension requiring > 2 medications for adequate control; diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months; chronic obstructive pulmonary disease (COPD) requiring > 2 hospitalizations in the preceding 12 months
  • Patients with a history of, or known autoimmune disease, but not limited to systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, ankylosing spondylitis, sarcoidosis, vasculitis, Wegener's granulomatosis, Hashimoto's thyroiditis, ulcerative colitis, Crohn's disease, Goodpasture's disease, multiple sclerosis, etc.
  • Patients with any other medical, psychiatric or social condition that would preclude their participation in the study, pose an undue medical hazard, interfere with the conduct of the study or interfere with interpretation of the study results
  • Patients taking sucralfate, palifermin or amifostine
  • Patients receiving hematopoietic growth factors
  • Patients currently taking, or who have taken within 30 days of the initiation of protocol therapy, any immunomodulatory therapy, including pharmacologic doses of glucocorticoids (topical and inhalation glucocorticoids are permitted), azathioprine, methotrexate, interferon-alpha, interferon-beta, interluekin-2, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, etc
  • Patients with a history of hypersensitivity reactions to any of the components of CBLB502 or cisplatin
  • Women who are pregnant or lactating or who are planning on becoming pregnant during the study or for 90 days after completion of the study
  • Patients who have received an investigational therapy within 4 weeks of signing the informed consent for the current study
  • Patients with a history of, patients who were treated for, or patients who are suspected of having, hepatitis B, and hepatitis C or human immunodeficiency virus (HIV); patients suspected of having any of these conditions should undergo appropriate evaluations prior to being enrolled in the study
  • Surgery with significant defect or flap in the oral cavity
  • Poor dentition or ill-fitting dental appliances (can be enrolled if this can be corrected by a dentist prior to start of radiation therapy)
  • Presence of other medical conditions causing mucositis (e.g., rheumatologic, gastroesophageal reflux, etc.)

About this study

Official title: A Phase I Study of CBLB502 in the Treatment of Patients With Poor Prognosis Advanced Squamous Cell Carcinomas of the Head and Neck Receiving Chemoradiotherapy

This phase I trial studies the side effects and best dose of entolimod in treating patients with stage III-IV or recurrent head and neck cancer. Biological therapies, such as entolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Entolimod may also prevent side effects caused by chemotherapy with cisplatin and radiation therapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving entolimod together with cisplatin and radiation therapy may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the Phase II dose of CBLB502 (entolimod) when given as weekly injections during irradiation with cisplatin, for patients with poor prognosis advanced squamous cell carcinomas of the head and neck receiving chemoradiotherapy.

SECONDARY OBJECTIVES:

  1. To describe the adverse event (AE) profile and the dose limiting toxicities of CBLB502 when administered weekly in combination with cisplatin and radiation therapy.

II. To determine the maximally tolerated dose (if observed) of CBLB502 in combination with cisplatin and radiation therapy.

III. To describe the pharmacokinetics (PK) of CBLB502 when administered in combination with cisplatin.

IV. To describe the pharmacodynamics (PD) of CBLC502 by examining plasma levels of various cytokines, including filgrastim (granulocyte-colony stimulating factor [G-CSF]), interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α).

  1. To describe any clinical activity of CBLB502 in the form of mitigation of mucositis.

VI. To describe the response rate to chemoradiotherapy in combination with CBLB502.

OUTLINE: This is a dose-escalation study of entolimod.

Patients undergo intensity-modulated radiation therapy (IMRT) 5 times per week for 7 weeks, receive cisplatin intravenously (IV) once weekly for 7 weeks, and entolimod subcutaneously (SC) on days 1, 8, 15, 22, 29, 36, and 43.

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

Being tested
entolimod, intensity-modulated radiation therapy, cisplatin, pharmacological study, laboratory biomarker analysis
Medical subject headings
Mucositis, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms

What participants receive

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

  • entolimodDrug

    Also called CBLB502, TLR5 agonist CBLB502, toll-like receptor 5 agonist CBLB502

    Given SC

  • intensity-modulated radiation therapyRadiation

    Also called IMRT

    Undergo IMRT

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01728480
Study groupRoleWhat they receive
Treatment (entolimod, IMRT, cisplatin)ExperimentalPatients undergo IMRT 5 times per week for 7 weeks, receive cisplatin IV once weekly for 7 weeks, and entolimod SC on days 1, 8, 15, 22, 29, 36, and 43.
Receives: Drug: entolimod; Radiation: intensity-modulated radiation therapy; Drug: cisplatin; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Adverse events defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0

    Summarized descriptively by time point (mean, standard deviation). All safety analyses will be presented by dose cohort and overall as well as examined for relation to demographic parameters (i.e., gender, weight, body surface area [BSA]) and covariance or dependence on PK, PD, or presence of anti-entolimod antibodies at baseline and/or the development of entolimod antibodies.

    Measured: Up to 3 months after completion of study treatment

  2. PK of entolimod when administered in combination with cisplatin and radiation therapy

    A population PK model will be developed utilizing the PK time points collected and used to estimate individual areas under the curve (AUCs) or clearance (CL) of entolimod. The effect of patient factors, such as demographics and ECOG status, on entolimod PK will be evaluated by the model to help explain the interpatient variability in PK. Entolimod AUC, as well as the observed Crnax, will then be tested for association changes in cytokine levels, such as G-CSF, IL-6, IL-8, IL- 10 and TNF-alpha.

    Measured: Predose, and at 2, 4, 6, 8, and 12 (+/- 2) hours postdose on Day 1

  3. The percentage of patients with mucositis, measured using the World Health Organization (WHO) mucositis global severity score and the oral mucositis daily questionnaire (OMDQ)

    The percentage of patients with mucositis will be tabulated overall and by dose level.

    Measured: Up to 3 months after completion of study treatment

Timeline

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

  1. First posted19 Nov 2012 (estimated)
  2. Study startJan 2014
  3. Primary completionOct 2015 (estimated)

Why it stopped: Financial Sponsor requested termination

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01728480
Sponsor's protocol ID
I 209611
Other IDs
NCI-2012-02140
Status last verified
Dec 2013
First submitted
13 Nov 2012
Last updated
11 Dec 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing entolimod, intensity-modulated radiation therapy and cisplatin in people with Mucositis and Recurrent Squamous Cell Carcinoma of the Hypopharynx, run by Roswell Park Cancer Institute.

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 13 inclusion and 19 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: withdrawn, as of the sponsor's last update on 11 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

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 withdrawn before enrolling participants, so there are no results.

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?

Adverse events defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 (time frame: Up to 3 months after completion of study treatment). The study lists 3 primary outcomes in all. 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 NCT01728480.

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 11 Dec 2013.

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