Nicotine Levels With Response Rates to Radiation Alone or With Chemo In Head & Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Kentucky
Sponsor:
Information provided by (Responsible Party):
Mahesh Kudrimoti, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01084733
First received: March 9, 2010
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

The objective of this study is to evaluate the relationship between serum nicotine levels and tumor response of squamous cell cancers of the head and neck (SCCHN) to radiotherapy alone or in combination with chemotherapy.

Correlation of RECIST response, volumatic response, pathologic response (in patients receiving post-treatment neck dissection), and hemodynamic response (tumor oxygenation and blood flow) will be performed.


Condition
Larynx Cancer
Lip Cancer
Oral Cavity Cancer
Pharyngeal Cancer
Oropharyngeal Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Correlative Study of Nicotine Levels With Response Rates to Therapy Using Radiation Alone or in Combination With Chemotherapy in Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Correlation of serum cotinine with volumetric response [ Time Frame: 2 years from start of treatment ] [ Designated as safety issue: No ]
    RECIST criteria will be used as a correlate for standardization of tumor response. Volumetric analysis may provide better assessment of bulky tumor size that may have a large necrotic or hypoxic component that may be resistant to treatment. Furthermore, volumetric analysis has been associated with a higher rate of concordance to response based upon RECIST criteria.


Secondary Outcome Measures:
  • Correlation of serum cotinine with toxicities during treatment. [ Time Frame: 90 days from start of treatment ] [ Designated as safety issue: No ]
    Toxicities will be graded using the National Cancer Institute (NCI) scale for acute and subacute toxicity and the Radiation Therapy Oncology Group's late toxicity scale.

  • Correlation of serum cotinine with time to progression. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Time to progression will be calculated as the time interval between the start of radiation treatment and the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

  • Correlation of serum cotinine with survival [ Time Frame: 5 years from start of treatment ] [ Designated as safety issue: No ]
    Survival will be calculated from the start of radiation to the date of death.

  • Correlation of serum cotinine with response to treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Both pathologic and radiographic response to therapy will be assessed where possible. Primary tumors will be assessed by the attending otolaryngologist by panendoscopy, with biopsies taken in the case of a question of response. Nodal disease response will be assessed by radiographic means. All patients will be assessed for response at the end of primary treatment.

  • Investigate the hemodynamic responses to different nicotine levels and different therapies (radiation alone, radiation + chemotherapy). [ Time Frame: End of Treatment ] [ Designated as safety issue: No ]
    Previous studies indicated that there is a significant increase in blood flow in the early two weeks of radiation therapy and decreases in the following weeks, while the tissue oxygen saturation tends to decline continually


Biospecimen Retention:   Samples Without DNA

Blood will be obtained weekly during the treatment phase. Serum will be collected and aliquoted into eppendorf tubes. Serum samples will be stored in -20C freezer until assayed for cotinine levels using Immulite immunoassay for cotinine (Immulite 2000 Assay, DPC, United States, Technical Services 800-372-1782).


Estimated Enrollment: 100
Study Start Date: August 2007
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Detailed Description:

The exposure to tobacco related carcinogens is highly dependent upon dose as well as interindividual characteristics of metabolism. Risk assessment of carcinogenic profiles for nicotine and its individual metabolites is complicated by interindividual variations in nicotine metabolism associated with quantitative nicotine exposure, gender, genetic polymorphisms, and behavioral and environmentally induced differences in nicotine metabolizing enzyme activities. Consequently, differences in smoking behavior or tobacco use have been correlated to differences in nicotine metabolism resulting in cessation strategies based upon tobacco use, nicotine dependence, and behavioral modification. Cotinine has been shown to be a reliable marker of nicotine exposure and more reflective of recent rather than acute nicotine use with better assessment of baseline nicotine levels. Therefore, subjects will have blood samples drawn weekly during radiation for cotinine analysis.

Radiation therapy efficacy is known to be dependent on tissue oxygen status. Since therapeutic treatment is less efficacious in patients with poorly vascularized/ hypoxic tumors, it is desirable to identify and target such patients for special treatment. Recent magnetic resonance imaging and computed tomography investigations have shown that there are significant blood flow changes during radiation or chemo-radiation therapy, suggesting that early blood flow may have prognostic value. Among those methods for oxygen and blood flow measurements, the near-infrared spectroscopy (NIRS) is more benefit with merit of non-invasive, portable, fast test, and inexpensive. Our instrument system combined near-infrared diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) is capable of monitoring tissue oxygen and blood flow simultaneously. This hybrid diffuse optical instrument has already been used for monitoring of therapeutic effects (e.g., radiation therapy, chemotherapy) in tumors in human head & neck and breast. In this study, we will use this hybrid instrument to investigate the hemodynamic responses to different therapies (radiation alone, radiation + chemotherapy) in patients with different nicotine levels. Baseline measurement of tissue oxygen saturation, total hemoglobin concentration and blood flow using a hybrid optical instrument (DRS for oxygen measurement and DCS for blood flow measurement). A hand-hold optical probe connected to the hybrid instrument will be placed on the head/neck tumor for about 3-5 minutes, then move it on the normal arm muscle for control purposeTumor oxygenation and flow measurements will be performed at the beginning of every week during the treatment period. During this monitoring process non-invasive blood pressure monitoring will also occur. Weekly optical measurements will be obtained during treatment.In this study we will investigate the hemodynamic responses to different nicotine levels and different therapies (radiation alone, radiation + chemotherapy).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Male or female aged 18 or older

Criteria

Inclusion Criteria:

  • A: Male or female aged 18 or older
  • B: Pathologically confirmed squamous cell carcinoma
  • C: Measurable disease using CT, MRI, or panendoscopy
  • D: Tumor sites to include:

Oropharynx Hypopharynx Oral cavity Larynx Measurable disease with no evidence of primary

  • E: Patients to be treated with radiotherapy or chemoradiotherapy as a primary treatment modality. Patients to be treated with radiotherapy in combination with platinum based chemotherapy will be considered for enrollment.
  • F: Nutritional status to include patients that do not require placement of a feeding tube as well as patients that are feeding tube dependent. However, patients requiring total parenteral nutrition prior to initiation of treatment will be excluded.
  • G: ECOG performance status of 0, 1 or 2.
  • H: Standard of care chemotherapy inclusion criteria to include:

    i: No evidence of active angina pectoris or ventricular arrhythmia's; no myocardial infarction within the last six months. (Patients with medically controlled hypertension or congestive heart failure are eligible.) ii: Absolute neutrophil count of > 1000/uL and platelet count > 100,000/uL iii: Serum total bilirubin < 1.5 mg/dL iv: Creatinine Clearance greater than 60 ml/min creatinine clearance to be calculated using the formula: (140 - age) x (wgt in kg) * (serum creatinine) x (72)

    * multiply by 0.85 for females v: If a pre-existing grade I neuropathy exists, patients must be willing to risk worsening neuropathy secondary to treatment. Patients with grade II or greater neuropathy will be excluded from study.

  • I: Standard of care treatment will require counseling against the use of tobacco products and can include nicotine replacement at the request of the patient and discretion of treating physician. Patients who continue to use tobacco products as well as patients using any form of cessation strategy (nicotine replacement, bupropion, or other) will be eligible for enrollment.
  • J: Patients enrolled on experimental studies will be considered for enrollment with final selection to be made by Dr. Kudrimoti, Dr. Warren, Dr. Arnold, and Dr. Valentino.
  • K: Ability to give informed consent

Exclusion Criteria:

  • A: Pregnant females. Males and females of childbearing potential must use effective contraception in order to prevent pregnancy during therapy.
  • B: Histology other than squamous cell carcinoma
  • C: Patients without measurable disease using CT, MRI, or panendoscopy
  • D: Patients eligible for surgical resection alone or with significant (> 25%) surgical tumor debulking prior to radiotherapy will not be considered for enrollment. Furthermore, patients who are otherwise not candidates for radiotherapy at the discretion of the treating physician will be excluded from enrollment.
  • E: Patients with a history of previous or current malignancy at other sites diagnosed within the last 5 years, with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain free of recurrence or metastases for greater than five years are eligible.
  • F: Patients with active infection will not be eligible for this protocol until the infection is treated and the symptoms have clinically resolved.
  • G: Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.
  • H: Patients with metastatic disease will not be eligible for this study.
  • I: Patients with grade II or greater peripheral neuropathy will be excluded from study.
  • J: Patients receiving medication to prevent mucositis (palifermin, amifostine, or other).
  • K: Patients requiring total parenteral nutritional support prior to the initiation of treatment will not be eligible for study.
  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: NCT01084733

Contacts
Contact: Marta Wood 859-257-3379 marta.wood@uky.edu

Locations
United States, Kentucky
Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Mahesh R Kudrimoti, MD         
Sponsors and Collaborators
Mahesh Kudrimoti
Investigators
Principal Investigator: Mahesh Kudrimoti, MD University of Kentucky
  More Information

No publications provided

Responsible Party: Mahesh Kudrimoti, Clinical Faculty, Radiation Medicine, University of Kentucky
ClinicalTrials.gov Identifier: NCT01084733     History of Changes
Other Study ID Numbers: NICOTINE-HN
Study First Received: March 9, 2010
Last Updated: December 17, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Mouth Neoplasms
Oropharyngeal Neoplasms
Head and Neck Neoplasms
Mouth Diseases
Neoplasms
Neoplasms by Site
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases
Nicotine
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Ganglionic Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014