Azacitidine and Cisplatin for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Phase I Study of Azacitidine in Combination With Cisplatin Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

To evaluate the safety and toxicity of azacitidine (5-azacitidine, Vidaza®) and cisplatin combination in patients with squamous cell carcinoma of head and neck (SCCHN).

Study Overview

• Status: Terminated
• Conditions: Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Azacitidine; Drug: Cisplatin

Detailed Description

Open-label, non-randomized and dose escalation study in which groups of 3-6 patients with squamous cell carcinoma of the head and neck will receive sequentially increased dosages of azacitidine SC injection in combination with a fixed dose of cisplatin IV injection until dose-limiting toxicity is demonstrated in 2 of the 6 patients.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically proven SCCHN that is either metastatic or has persisted or recurred following definitive surgery and/or radiation therapy, and is not amenable to salvage surgical resection.
• Patients may have received previous chemotherapy and/or biological treatment (such as cetuximab) for the recurrent or metastatic disease. Prior treatment must have been completed at least 28 days (42 days for nitrosoureas or mitomycin C) prior to entering the study and all toxicities must have been resolved.
• Prior radiation must have been completed at least 28 days before entry into the study and all toxicities must have been resolved (no more than 3000 cGy to fields including substantial marrow).
• Surgery must have been completed at least 28 days before entry into the study and all complications/adverse events must have been resolved.
• Patients must have at least one lesion amenable to serial biopsy.
• Age greater than 18 years.
• ECOG performance status less than 2 (Karnofsky greater than 60%).
• Life expectancy of greater than 3 months.
• Patients must have normal organ and marrow function
• Patients must not be planning to receive any other concurrent therapy (ie, radiation, chemotherapy, immunotherapy, biological therapy or gene therapy) for SCCHN while they are on this study.
• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.

Exclusion Criteria:

• Patients must not be planning to receive any other concurrent therapy (ie, radiation, chemotherapy, immunotherapy, biological therapy, investigational agents or gene therapy) for SCCHN while they are on this study.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, cisplatin and mannitol or other agents used in study.
• Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• 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.
• Patients known to be HIV-positive are not eligible because of the potential to confound this study's endpoints.
• No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 (SCCHN); Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Patients will receive Azacitidine and cisplatin.	Drug: Azacitidine; SC azacitidine; Other Names: 5-azacitidine, Vidaza; Drug: Cisplatin; cisplatin 75 mg/m^2 day 8 every 28 days; Other Names: cis-platinum, platinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Safety and Toxicity of Azacitidine (5-azacytidine, Vidaza®) and Cisplatin Combination	Although response is not the primary endpoint of this trial, patients with measurable disease will by assessed by standard criteria. For the purpose of this study, patients should be re-evaluated every 8 weeks by imaging study. In addition to baseline scan, confirmatory scans will also be obtained 4 weeks following initial documentation of an objective response.	Weeks 1-12, 24, 36

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Celgene Corporation
• Investigators: Study Director: Stephen K. Williamson, MD, University of Kansas Medical Center; Study Chair: Chao H. Huang, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: March 2, 2007
• First Submitted That Met QC Criteria: March 2, 2007
• First Posted (Estimate): March 5, 2007

Study Record Updates

• Last Update Posted (Actual): February 27, 2017
• Last Update Submitted That Met QC Criteria: January 8, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Head and Neck Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: 10498

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO