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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
David Schuller, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00566540
First received: November 30, 2007
Last updated: January 7, 2013
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Cisplatin
Drug: Paclitaxel
Radiation: Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation
Procedure: Triple endoscopy and biopsy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Feasibility of treatment [ Time Frame: Up to one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free interval and failure sites [ Time Frame: Up to one year ] [ Designated as safety issue: No ]
  • Correlation of molecular markers with treatment outcome [ Time Frame: Up to week 14 ] [ Designated as safety issue: No ]
  • Correlation of quality of life with treatment outcome [ Time Frame: Up to one year ] [ Designated as safety issue: No ]
  • Frequency and severity of toxicities [ Time Frame: Up to one year ] [ Designated as safety issue: Yes ]
  • Treatment completion [ Time Frame: up to one year ] [ Designated as safety issue: No ]
    Patients are to be seen at Ohio State Medical center for a physical exam every 2 months for the first year.


Estimated Enrollment: 50
Study Start Date: December 2007
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Cisplatin
Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.
Other Names:
  • Platinol-®AQ
  • cis-DDP
  • cis-Diamminedichloroplatinum
  • cis-Platinum II
  • DDP
Drug: Paclitaxel
Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10
Other Name: Taxol®
Radiation: Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation
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:
  • radiation therapy
  • EBT
  • IMRT
Procedure: Triple endoscopy and biopsy
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.

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.

  Eligibility

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

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.
  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: NCT00566540

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: David E. Schuller, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: David Schuller, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00566540     History of Changes
Other Study ID Numbers: OSU-06026, NCI-2011-02687
Study First Received: November 30, 2007
Last Updated: January 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage II squamous cell carcinoma of the hypopharynx

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cisplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014