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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

Brief 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. 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 Summary:

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
Sponsor: Roswell Park Cancer Institute

Current Primary Outcome:

  • 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 ]
    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.
  • PK of entolimod when administered in combination with cisplatin and radiation therapy [ Time Frame: Predose, and at 2, 4, 6, 8, and 12 (+/- 2) hours postdose on Day 1 ]
    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.
  • The percentage of patients with mucositis, measured using the World Health Organization (WHO) mucositis global severity score and the oral mucositis daily questionnaire (OMDQ) [ Time Frame: Up to 3 months after completion of study treatment ]
    The percentage of patients with mucositis will be tabulated overall an

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Roswell Park Cancer Institute

    Dates:
    Date Received: November 13, 2012
    Date Started: January 2014
    Date Completion:
    Last Updated: December 10, 2013
    Last Verified: December 2013