Ph 2 Intensification Regimen for Previously Untreated, Resectable, Advanced Squamous Cell Cancer

October 29, 2021 updated by: Enver Ozer, Ohio State University Comprehensive Cancer Center

Intensification Regimen for Previously Untreated, Resectable, Advanced Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, and Hypopharynx: Incorporation of Intensity Modulated Radiotherapy and Submandibular Gland Transfer to Minimize Treatment Morbidity; Correlative Imaging/Molecular Markers.

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving cisplatin and paclitaxel together with radiation therapy and surgery works in treating patients with advanced cancer of the oral cavity, oropharynx, or hypopharynx that can be removed by surgery.

Study Overview

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility of a new intensification regimen comprising cisplatin and paclitaxel in combination with radiotherapy and surgery in patients with resectable advanced squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx.

Secondary

  • Assess the disease-free interval and failure sites in patients treated with this regimen.
  • Correlate molecular markers with treatment outcome in these patients.
  • Correlate quality of life with treatment outcome in these patients.
  • Determine the frequency and severity of toxicities of this regimen in these patients.
  • Evaluate treatment completion in these patients.

OUTLINE:

  • Preoperative therapy (weeks 1 and 2): Patients receive cisplatin IV over 2 hours on days 1-3. Patients also undergo intensity-modulated external beam radiotherapy once daily on days 1-5 and 8-12.
  • Surgery (week 3): Patients undergo surgical resection of the primary tumor (with or without neck dissection) and intraoperative boost radiotherapy.
  • Postoperative therapy (weeks 7-10): Patients receive cisplatin IV over 2 hours on days 1-3 and 22-24 and paclitaxel IV over 3 hours on days 1, 8, 15, and 22. Patients also undergo intensity-modulated external beam radiotherapy on days 1-5, 8-12, 15-19, and 22-26.

Patients undergo blood and tissue sample collection at baseline, in weeks 3, 7-10, and 14, and then periodically thereafter for biomarker correlative studies.

Quality of life is assessed at baseline, at 3, 6, and 12 months after completion of treatment, and then annually thereafter.

After completion of study treatment, patients are followed every 2 months for 1 year and then periodically thereafter.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 a Karnofsky Performance Index ≥60%
  • Patients must be over the age of 18.
  • Patients must have a life expectancy of at least 6 months.
  • Women of childbearing age must have a negative serum pregnancy test and agree to use an effective method of contraceptive.
  • Patients with a cardiac history should be cleared with a medical internist. In general, patients with a history of prior bradyarrythmias, atrioventricular (AV) conduction defects or marginal cardiac function will be eligible.
  • Patients must have resectable stage III, stage IVA, stage IVB (without distant metastases) squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx. Hypopharyngeal carcinomas may also be stage II.
  • Patients must not have had prior chemotherapy or radiotherapy (to the primary site or nodes).
  • Patients may not be planning to receive while on study concomitant immunotherapy or hormonal therapy, except oral contraceptives or hormone replacement therapy.
  • Patients must have adequate hepatic function documented by a normal serum bilirubin 0- 1.5mg/L and serum transaminases < 4 x upper limit.
  • Patients must have adequate renal function documented by a serum creatinine not above upper institutional normal limits and/or 24 hour OR calculated creatinine clearance >60 ml/min. using the following formula:

    (140-age) x Wt (kg) x .85 (if Estimated Creatinine Clearance = 72 x Creatinine (mg/dl) female)

  • Patients must have adequate bone marrow function documented by platelet count ≥ 100,000 and absolute neutrophil count ≥ 2,000.
  • Patients will have surgery according to Section 5.3. Operative and pathology reports must be sufficiently detailed to confirm that surgery was done according to the guidelines.
  • Patients must be examined by a multi-modality team (consisting of a head and neck surgeon, medical oncologist, and radiation oncologist) prior to entry on study.
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  • Distant metastases.
  • Prior malignancy, 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.
  • Any condition that would be considered a contraindication for fluid challenge.
  • Pregnant or lactating women may not participate.
  • History of demyelinating neurological disorder, such as multiple sclerosis
  • History of pancytopenia or aplastic anemia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (neoadjuvant, adjuvant chemotherapy and radiation)

PREOPERATIVE:Patients receive cisplatin IV over 2 hours three times weekly in week 1 once daily(QD),5 days a week, in weeks 1-2.

SURGERY:Patients undergo triple endoscopy and biopsy with submandibular gland transfer in week 3.

INTRAOPERATIVE: Patients also undergo Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation.

POSTOPERATIVE: Patients receive paclitaxel IV over 3 hours in weeks 7-10 and cisplatin IV over 1-2 hours three times weekly in weeks 7 and 10. Patients also undergo Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation QD, 5 days a week, in weeks 7-10.

Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.
Other Names:
  • DDP
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • Platinol-®AQ
Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10
Other Names:
  • Taxol®
Patients will receive Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation to tumor and involved regional nodes 20Gy over 10 daily (M-F) treatments (2 Gy Fractions with 6 millivolts photons)week 1 and 2.
Other Names:
  • IMRT
  • radiation therapy
  • EBT
Resection of the primary tumor: Patients must have surgery performed according to the following surgical guidelines. The extent of the surgical resection will be dictated by the extent of the tumor at the time of initial evaluation. The primary lesion must be widely excised using accepted criteria for adequate excision depending on the region involved. All patients will undergo percutaneous endoscopic gastrostomy tube placement at the time of endoscopy and biopsies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of Treatment
Time Frame: Up to one year
Determine the feasibility of a new intensification regimen for previously untreated resectable advanced stage head and neck cancer that incorporates Cisplatin, Paclitaxel combined with surgery, submandibular gland transfer and radiation therapy
Up to one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Interval and Failure Sites
Time Frame: Up to one year
Assess disease-free interval and failure sites of a new treatment regimen.
Up to one year
Correlation of Quality of Life With Treatment Outcome
Time Frame: Up to one year
Assess quality of life with treatment outcome will be obtained at baseline (prior to treatment) and at 6 months post treatment and one year post-treatment follow-ups.
Up to one year
Percentage of Participants With Serious Adverse Events
Time Frame: Up to one year
Determine the frequency and severity of toxicities of the intensification regimen. Patients will be evaluated for local and systemic toxicity/morbidity from treatment regimen.
Up to one year
Treatment Completion
Time Frame: up to one year
Patients are to be seen at Ohio State Medical center for a physical exam every 2 months for the first year.
up to one year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of Molecular Markers With Treatment Outcome
Time Frame: Up to week 14
Evaluate potential correlative molecular markers with treatment outcome
Up to week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Enver Ozer, MD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2007

Primary Completion (Actual)

February 25, 2010

Study Completion (Actual)

February 25, 2010

Study Registration Dates

First Submitted

November 30, 2007

First Submitted That Met QC Criteria

November 30, 2007

First Posted (Estimate)

December 3, 2007

Study Record Updates

Last Update Posted (Actual)

November 26, 2021

Last Update Submitted That Met QC Criteria

October 29, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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