Phase I Trial of Biweekly Gemcitabine & Paclitaxel & Low-Dose Radiation for Metastatic or Recurrent Head & Neck Cancer

This study has been terminated.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
University of Kentucky
ClinicalTrials.gov Identifier:
NCT00176241
First received: September 12, 2005
Last updated: January 27, 2010
Last verified: January 2010
  Purpose

This study seeks to establish the safety of gemcitabine, paclitaxel and low-dose radiation in recurrent, metastatic head and neck cancer through a two-stage dose escalation study, first with Gemcitabine dose escalation and then with low-dose radiation escalation.

Treatment Schedule

Treatment will be administered on an inpatient or outpatient basis.

  • Gemcitabine:2000 to 3000mg/m2 IV (in the vein) on days 1 and 15 every 28 days over 30-60 minutes.
  • Paclitaxel: 150 mg/m2 IV(in the vein)on days 1 and 15 every 28 days over 60 minutes.
  • Low Dose Radiation: 50-80 cGy twice daily on days 1, 2, 15, & 16 every 28 days at least 4 hours apart.

Condition Intervention Phase
Head and Neck Cancer
Drug: gemcitabine
Drug: paclitaxel
Radiation: radiation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Biweekly Gemcitabine & Paclitaxel & Low-Dose Fractionated Radiation in the Treatment of Metastatic or Recurrent Head & Neck Cancer

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: toxicity notations made during weeks 3, 5, 7 & 9 of each cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: weeks 3, 5, 7 & 9 of each cycle & also evaluated throughout study by weekly CBC ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: assessed pre-study & week 8 and as needed during follow-up. ] [ Designated as safety issue: No ]
  • Association of tumor markers p53, p21waf1/cip1, bcl-xL, bcl-2 & bax with response rate [ Time Frame: patients who consent to biopsy, obtain pre-study & 3-24 hrs after completion of 4th fraction of radiation, evaluated by immunohistochemistry ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: December 2005
Estimated Study Completion Date: November 2009
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: gemcitabine
2000-3000mg/m2 IV on days 1 & 15
Other Name: Gemzar
Drug: paclitaxel
150 mg/m2 IV on days 1 & 15
Radiation: radiation
50-80 cGy on days 1,2,15,16

Detailed Description:

Objectives:

1. To assess the MTD of low-dose fractionated radiation in combination with Gemcitabine and Paclitaxel in recurrent or metastatic head and neck cancer in the relapsed setting.

Secondary Objectives:

  1. To assess quantitative toxicities in this group of patients treated with this regimen.
  2. To assess response rate in this group of patients treated with this regimen
  3. To investigate in an exploratory manner, the association of tumor markers p53, p21waf1/cip1, bcl-xL, bcl-2 and bax (evaluated by immunohistochemistry) with response rate using pre- and post-treatment biopsies.

This study seeks to establish the safety of gemcitabine, paclitaxel and low-dose radiation in recurrent, metastatic head and neck cancer through a two-stage dose escalation study, first with Gemcitabine dose escalation and then with low-dose radiation escalation.

Treatment Schedule:

Treatment will be administered on an inpatient or outpatient basis.

  • Gemcitabine:2000 to 3000mg/m2 IV on days 1 and 15 every 28 days over 30-60 minutes.
  • Paclitaxel: 150 mg/m2 IV on days 1 and 15 every 28 days over 60 minutes.
  • Low Dose Radiation: 50-80 cGy twice daily on days 1, 2, 15, & 16 every 28 days at least 4 hours apart.
  Eligibility

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

Inclusion Criteria:

  1. 18 yrs old or greater & have histologically or cytologically proven metastatic or recurrent head & neck cancer & have failed at least 1 prior, but not more than 3 chemotherapeutic regimen. Patients who have recurred after previous surgery and/or radiation may participate in this trial, & patients may have had prior neoadjuvant or adjuvant therapy. No restriction is placed on the # of cycles (beyond 1) of prior therapy, however, patients must not have received the combination of Gemcitabine & Paclitaxel previously.
  2. Patients with known brain metastases are eligible for this trial if disease has been treated & the patient is clinically stable & documented by a stable or improved pretreatment CT or MRI of the brain to evaluate CNS disease within 28 days prior to registration.
  3. Patients must have measurable OR non-measurable disease documented by CT, MRI, X-ray or nuclear exam (FDG-PET). Measurable disease must be assessed within 28 days prior to registration & non-measurable must be assessed within 42 days prior to registration. Pleural effusions, ascites & lab parameters are not acceptable as only evidence of disease.
  4. Patients must have progressed after at least 1 prior chemotherapeutic regimen. Prior biologic therapy or radiation is permitted; however, at least 2 wks must have elapsed since completion of prior therapy & patients must have recovered from all associated toxicities at time of registration.
  5. At least 3 wks must have elapsed since surgery (thoracic or other major surgeries) & patients must have recovered from all associated toxicities at time of registration. Measurable or non-measurable disease must be present outside the area of surgical resection.
  6. Patients must have an ANC 1,500/µl & platelet count 100,000/µl obtained within 28 days prior to registration.
  7. Patients must have adequate hepatic function documented by a serum bilirubin 1.5 x institutional ULN & LFTs (SGOT or SGPT) 2.5 x the institutional ULN obtained within 28 days prior to registration.
  8. All patients with pulmonary metastasis must have an FEV1 of > 1000 ml/min obtained within 28 days prior to registration & must have PFTs with DLCO.
  9. All patients must have a Zubrod Performance Status of 0,1 or 2.
  10. Peripheral neuropathy, if present, must be Grade 1.
  11. Patients must be informed of investigational nature of this study & must sign & give written informed consent in accordance with institutional & federal guidelines.

Exclusion Criteria:

  1. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 5 yrs.
  2. 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 (hormonal or barrier method of birth control; abstinence) prior to study entry & for duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  3. Patients taking drugs that are strong inducers of the enzyme CYP3A4 including anticonvulsants (i.e., phenytoin, phenobarbital, carbamazepine, or primidone) & rifampin OR strong inhibitors of CYP3A4 (clarithromycin, itraconazole, and ketoconazole) will be excluded from this study. Patients must be off these medications for 2 wks in order to participate in this trial.
  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: NCT00176241

Locations
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
University of Kentucky
Eli Lilly and Company
Investigators
Principal Investigator: Susanne Arnold, MD University of Kentucky
  More Information

Additional Information:
No publications provided

Responsible Party: Susanne Arnold, MD, Associate Professor of Medicine, University of Kentucky
ClinicalTrials.gov Identifier: NCT00176241     History of Changes
Other Study ID Numbers: 04-H&N-16-EL
Study First Received: September 12, 2005
Last Updated: January 27, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by University of Kentucky:
head and neck
Gemcitabine
Paclitaxel
radiation
low-dose radiation
recurrent
metastatic

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Gemcitabine
Paclitaxel
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014