Azacitidine and Cisplatin in Patients With Advanced Lung or Head and Neck Cancer

This study has been terminated.
(Sponsor terminated due to no enrollments within last 4 months.)
Sponsor:
Information provided by (Responsible Party):
Chung-Tsen Hsueh, Loma Linda University
ClinicalTrials.gov Identifier:
NCT00901537
First received: May 12, 2009
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

The standard of care for head and neck and lung cancer includes chemotherapy, radiation and surgery. For patients with cancer of head and neck or lung that recurs after surgery and/or radiation, or has spread to other parts of body, chemotherapy using cisplatin can slow down tumor growth and extend lifespan.

The study drug, azacitidine, can block the ability of some cancer cells to replicate, and has been approved by the Food and Drug Administration for use in myelodysplastic syndrome, which is a slowly developing blood cell-related cancer. In laboratory and animal experiments using head and neck and lung cancer cells, azacitidine has been shown to be a cisplatin "helper", (that is, it makes cisplatin more effective in stopping the growth of head and neck and lung cancer. )

Since the combination of azacitidine and cisplatin has not been used in patients with head and neck or lung cancer, the investigators are performing this study combining azacitidine and cisplatin to find out what effects, good and/or bad, the study drug may have on patients with advanced head and neck or lung cancer. The investigators are doing this study because they would like to find a better treatment for these types of cancer.


Condition Intervention Phase
Non-small Cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Drug: Azacitidine and Cisplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Azacitidine in Combination With Cisplatin in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer or Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Loma Linda University:

Primary Outcome Measures:
  • Evaluate the safety and toxicity of azacitidine and cisplatin combination. [ Time Frame: weekly for first 4 weeks, then weekly times 2 for every 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the biologically effective dose of azacitidine, maximum tolerated dose of azacitidine and cisplatin combination, and tumor response [ Time Frame: every 8 weeks for response evaluation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: February 2009
Study Completion Date: October 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine and Cisplatin
Every 4 weeks, azacitidine is given daily as subcutaneous injection for 5 days from day 1 to day 5, and cisplatin is given as intravenous injection on day 8. The dose of azacitidine will be dose escalated among each group of 3-6 patients, and the dose of cisplatin is fixed.
Drug: Azacitidine and Cisplatin
We plan to give azacitidine daily as subcutaneous injection at escalated doses (37, 60, 75, 85, 100 and 110 mg/m2) for 5 days from day 1 to day 5, and give cisplatin 75 mg/m2 as intravenous injection on day 8, every 4 weeks as a cycle.
Other Names:
  • Vidaza
  • 5-Azacytidine

Detailed Description:

Azacitidine will be given with standard dose of cisplatin. At the beginning of the study, three patients will be treated with low dose of azacitidine. If that dose does not cause bad side effects, then the dose will slowly be made higher for new patients who take part in the study.

Patients will receive azacitidine as a once-a-day subcutaneous (under the skin) injection every day from day 1 to day 5 of 28 days in this study. Cisplatin is given intravenously on day 8. This 28-day or 4-week period of time is called a cycle. Cycles are repeated every four weeks for as long as the physician recommends.

During this study, patients will need the following tests and procedures.

  • Physical exam - This will be done weekly during first 2 weeks of every 4-week treatment cycle.
  • Blood tests for blood counts - These will be done every week.
  • Blood tests for kidney function, liver function, and to measure electrolytes - These will be done every week
  • Blood samples for research study - This will be done weekly during first cycle, then weekly during the first 2 weeks on the subsequent treatment cycles
  • X-rays or scans - These will be done once every 8 weeks.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically proven squamous cell carcinoma of head and neck or non-small cell lung cancer 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, bevacizumab or erlotinib) 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. Patients who have received prior treatment with EGFR inhibitor alone such as cetuximab or erlotinib are allowed to enter the study at least 14 days after receiving the last dose of the prior treatment.
  • 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 28 days before entry into the study and all complications/adverse events must have been resolved.
  • Age >18 years.
  • ECOG performance status <2 (Karnofsky >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 (i.e. radiation, chemotherapy, immunotherapy, biological therapy or gene therapy) while they are on this study.
  • Patients must be able to understand and sign a written informed consent document approved for this trial.
  • Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.

Exclusion Criteria:

  • Patients with symptomatic brain metastases are excluded from this clinical trial. Patients with asymptomatic brain metastases are allowed. The patient must be stable for 2 weeks after radiotherapy; if the patient is on corticosteroids, the dose of cortico steroids must have been stable for 2 weeks prior to first dose of study treatment, or be in the process of being tapered.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00901537

Locations
United States, California
Loma Linda University Cancer Center
Loma Linda, California, United States, 92354
Sponsors and Collaborators
Loma Linda University
Investigators
Principal Investigator: Chung-Tsen Hsueh, MD, PhD Loma Linda University Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Chung-Tsen Hsueh, MD PhD, Loma Linda University
ClinicalTrials.gov Identifier: NCT00901537     History of Changes
Other Study ID Numbers: 58358, IND 105076 (IND Exempt)
Study First Received: May 12, 2009
Last Updated: June 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Loma Linda University:
Non-small Cell Lung Cancer
Head and Neck Cancer
Azacitidine
Vidaza
Cisplatin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Azacitidine
Cisplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014