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

NCT ID: NCT00566540

Last Updated: 2021-11-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-11

Study Completion Date

2010-02-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Head and Neck Cancer

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.

Paclitaxel

Intervention Type DRUG

Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10

Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation

Intervention Type 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.

Triple endoscopy and biopsy

Intervention Type PROCEDURE

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.

Interventions

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Cisplatin

Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.

Intervention Type DRUG

Paclitaxel

Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10

Intervention Type DRUG

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.

Intervention Type RADIATION

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.

Intervention Type PROCEDURE

Other Intervention Names

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Platinol-®AQ cis-DDP cis-Diamminedichloroplatinum cis-Platinum II DDP Taxol® radiation therapy EBT IMRT

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Enver Ozer

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Enver Ozer, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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NCI-2011-02687

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-06026

Identifier Type: -

Identifier Source: org_study_id