Phase II Trial of Pemetrexed-Based Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Previously Irradiated Head and Neck Cancer Patients

• ClinicalTrials.gov Identifier: NCT01172470
• Recruitment Status: Completed
• First Posted: July 29, 2010
• Last Update Posted: January 17, 2014
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Study Description

Brief Summary:

The purpose of this study is to determine 1-year survival of previously irradiated Head and Neck cancer (HNC) patients with loco-regional recurrent disease treated with induction chemotherapy with pemetrexed and gemcitabine followed concomitant pemetrexed, carboplatin and daily radiotherapy.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Drug: Gemcitabine; Drug: Pemetrexed; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Pemetrexed-Based Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Previously Irradiated Head and Neck Cancer Patients
• Study Start Date: June 2005
• Actual Primary Completion Date: June 2007
• Actual Study Completion Date: July 2010

Arms and Interventions

Intervention Details:

• Drug: Gemcitabine
  4 doses of induction chemotherapy every 2weeks, IV (in the vein)
• Drug: Pemetrexed

  Induction Chemotherapy:

  4 doses of induction chemotherapy every 2weeks(Days 1, 15, 28, and 42), through an infusion for approximately 10 minutes.

  Chemoradiotherapy:

  Day 1,22, and 43through IV infusion over a period of 10 minutes

• Drug: Carboplatin

  Chemoradiotherapy:

  Day 1, 22 and 4 through IV infusion over a period of 1 hour.

Outcome Measures

Primary Outcome Measures :

1. Primary objective is to determine 1-year survival of previously irradiated Head/Neck Cancer patients with loco-regional recurrent disease treated with induction chemotherapy with pemetrexed and gemcitabine followed by concomitant pemetrexed, carboplat [ Time Frame: 1-3 years ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• All previously irradiated patients with recurrent head and neck cancer with no clinically measurable distant disease or those patients in whom distant disease was of low volume and local and regional palliation is clinically warranted. Low volume metastatic disease is defined as asymptomatic or minimally symptomatic disease that, according to physician judgment and without therapy for locoregionally recurrent disease, is unlikely to effect the subject's quality or quantity of life.
• Histologic or cytological documentation of recurrent head and neck cancer requiring regional therapy.
• Prior radiation therapy completed > 4 months before to study entry, if patients have recovered from all side effects grade 1.
• Predominance of disease that is amenable to radiotherapy.
• Measurable disease prior to induction chemotherapy.
• Age >18 years
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 70%).
• Patients must have normal organ and marrow function as defined below:

Leukocytes >3,000/ul Absolute neutrophil count >1,500/ul Platelets >100,000/ul Total bilirubin < 1.5X institutional upper limit of normal AST (SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal Creatinine Clearance (CrCl) > 45 mL/min

The standard Cockcroft and Gault formula (based on actual weight) or the measured glomerular filtration rate (GFR) using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl for enrollment or dosing. The same method used at baseline should be used throughout the study. Insufficient numbers of patients have been studied with creatinine clearance <45 mL/min to give a dose recommendation. Therefore, pemetrexed should not be administered to patients whose creatinine clearance is <45 mL/min.

Although ibuprofen and other non-steroidal inflammatory drugs (NSAID) can be administered with pemetrexed in patients with normal renal function (creatinine clearance 80 mL/min), caution should be used when administering NSAID concurrently with pemetrexed to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min). Patients with mild to moderate renal insufficiency should avoid taking NSAID with short elimination half lives (e.g. ibuprofen) for a period of 2 days before, the day of, and 2 days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAID with longer half lives, all patients taking these NSAID should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal, and gastrointestinal toxicity.

• The presence of a significant infection or another severe complicating medical illness may constitute a contraindication to entrance on this protocol.
• Pregnancy is an absolute contraindication for this treatment protocol.
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow vitamins and dexamethasone or willingness to use a feeding tube to ingest these agents

Exclusion Criteria:

Previously untreated patients are not eligible

Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

Patients may not be receiving any other investigational agents.

History of allergic reactions attributed to compounds of similar chemical composition agents used in the study.

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.

Contacts and Locations

Locations

United States, Illinois

The University of Chicago Medical Center

Chicago, Illinois, United States, 60653

Sponsors and Collaborators

University of Chicago

Investigators

• Principal Investigator: Ezra Cohen, MD; The University of Chicago Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ziliak D, O'Donnell PH, Im HK, Gamazon ER, Chen P, Delaney S, Shukla S, Das S, Cox NJ, Vokes EE, Cohen EE, Dolan ME, Huang RS. Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers. Transl Res. 2011 May;157(5):265-72. doi: 10.1016/j.trsl.2011.01.005. Epub 2011 Feb 8.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT01172470
• Other Study ID Numbers: 13881B
• First Posted: July 29, 2010
• Last Update Posted: January 17, 2014
• Last Verified: January 2014

Keywords provided by University of Chicago:

Recurrent head and neck cancer; larynx, lip, oral cavity and pharynx

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Gemcitabine; Carboplatin; Pemetrexed; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors