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

NCT ID: NCT01728480

Last Updated: 2013-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Brief Summary

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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

Detailed Description

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PRIMARY OBJECTIVES:

I. 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:

I. 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).

V. 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.

Conditions

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Mucositis Recurrent Squamous Cell Carcinoma of the Hypopharynx Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Squamous Cell Carcinoma of the Oropharynx Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Recurrent Verrucous Carcinoma of the Larynx Recurrent Verrucous Carcinoma of the Oral Cavity Stage III Squamous Cell Carcinoma of the Hypopharynx Stage III Squamous Cell Carcinoma of the Larynx Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity Stage III Squamous Cell Carcinoma of the Nasopharynx Stage III Squamous Cell Carcinoma of the Oropharynx Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage III Verrucous Carcinoma of the Larynx Stage III Verrucous Carcinoma of the Oral Cavity Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IVA Squamous Cell Carcinoma of the Larynx Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVA Squamous Cell Carcinoma of the Oropharynx Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVA Verrucous Carcinoma of the Larynx Stage IVA Verrucous Carcinoma of the Oral Cavity Stage IVB Squamous Cell Carcinoma of the Larynx Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVB Squamous Cell Carcinoma of the Oropharynx Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVB Verrucous Carcinoma of the Larynx Stage IVB Verrucous Carcinoma of the Oral Cavity Stage IVC Squamous Cell Carcinoma of the Larynx Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVC Squamous Cell Carcinoma of the Oropharynx Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVC Verrucous Carcinoma of the Larynx Stage IVC Verrucous Carcinoma of the Oral Cavity Tongue Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (entolimod, IMRT, cisplatin)

Patients 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.

Group Type EXPERIMENTAL

entolimod

Intervention Type DRUG

Given SC

intensity-modulated radiation therapy

Intervention Type RADIATION

Undergo IMRT

cisplatin

Intervention Type DRUG

Given IV

pharmacological study

Intervention Type OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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entolimod

Given SC

Intervention Type DRUG

intensity-modulated radiation therapy

Undergo IMRT

Intervention Type RADIATION

cisplatin

Given IV

Intervention Type DRUG

pharmacological study

Correlative studies

Intervention Type OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CBLB502 TLR5 agonist CBLB502 toll-like receptor 5 agonist CBLB502 IMRT CACP CDDP CPDD DDP pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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.)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Cleveland BioLabs, Inc.

INDUSTRY

Sponsor Role collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anurag Singh

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Countries

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United States

Other Identifiers

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NCI-2012-02140

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 209611

Identifier Type: -

Identifier Source: org_study_id