S0011, Gene Therapy & Surgery Followed by Chemo & RT in Newly Diagnosed Cancer of the Mouth or Throat

Sponsor

Southwest Oncology Group (Other)

Overall Status

Terminated

CT.gov ID

NCT00017173

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

100.9

Duration (Months)

4.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Inserting the p53 gene into a person's cancer cells may improve the body's ability to fight cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy with the p53 gene may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of gene therapy plus surgery followed by cisplatin and radiation therapy in treating patients who have newly diagnosed resectable stage III or stage IV cancer of the mouth or throat.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: Ad5CMV-p53 gene Drug: cisplatin Procedure: conventional surgery Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the feasibility of treating patients with newly diagnosed resectable stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with surgery and Ad5CMV-p53 gene followed by cisplatin and radiotherapy.
Determine the progression-free survival, local control, and overall survival of patients treated with this regimen.
Determine the toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

Patients undergo surgical resection and receive an intraoperative Ad5CMV-p53 gene injection into the resection bed and into the deep soft tissue bed of the cervical level with nodal metastasis. Patients also receive a third intraoperative Ad5CMV-p53 gene injection into the neck dissection bed, where it is allowed to sit in place for 10 minutes.

Within 48-72 hours after surgery, patients receive a postoperative Ad5CMV-p53 gene injection into each of two drainage catheters next to the mucosal suture line and neck dissection bed, where it is allowed to sit in place for 2 hours.

Within 56 days after surgery, patients receive cisplatin IV over 30-90 minutes on days 1, 22, and 43 and radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients may receive 3 additional days of radiotherapy to high-risk areas on days 43-45.

Patients are followed every 2-6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial Of Surgery With Perioperative RPR/INGN 201 (Ad5CMV-p53) Gene Therapy Followed By Chemoradiotherapy For Advanced, Resectable Squamous Cell Carcinoma Of The Oral Cavity, Oropharynx, Larynx, and Pharynx

Study Start Date :

Feb 1, 2003

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: surgery with INGN 201 followed by chemo/RT intraoperative and postoperative injections of INGN 201 into the tumor bed, followed by cisplatin and radiation therapy	Biological: Ad5CMV-p53 gene 2 intraoperative and one post-operative injection of Ad5CMV-p53. Other Names: INGN 201 Drug: cisplatin 100 mg/m2 IV Day 1 every 21 days for 3 cycles Other Names: platinol Procedure: conventional surgery conventional surgery Other Names: surgery Radiation: radiation therapy 200 cGy per day Days 105 every week for 6 weeks Other Names: RT

Arm

Intervention/Treatment

Experimental: surgery with INGN 201 followed by chemo/RT

intraoperative and postoperative injections of INGN 201 into the tumor bed, followed by cisplatin and radiation therapy

Biological: Ad5CMV-p53 gene

2 intraoperative and one post-operative injection of Ad5CMV-p53.

Other Names:

INGN 201

Drug: cisplatin

100 mg/m2 IV Day 1 every 21 days for 3 cycles

Other Names:

platinol

Procedure: conventional surgery

conventional surgery

Other Names:

surgery

Radiation: radiation therapy

200 cGy per day Days 105 every week for 6 weeks

Other Names:

Outcome Measures

Primary Outcome Measures

Feasibility [1 year]
accrual rate and percentage of patients successfully receiving the required doses of INGN 201

Secondary Outcome Measures

Progression-free survival from time of registration until disease progression [two years]
percentage of patient who have not experience progression of disease at two years

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed high-risk/limited stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx
Newly diagnosed
Previously untreated
Considered surgically resectable
Evidence of regional lymph node metastases (N1-N3)
No distant metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
SGOT or SGPT no greater than 3 times ULN
Hepatitis B surface antigen negative
Hepatitis C antibody negative

Renal:

Creatinine no greater than 2 times ULN
Creatinine clearance at least 60 mL/min

Other:

Magnesium normal (magnesium supplement allowed)
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission
HIV negative
Not pregnant or nursing
Patients must use effective barrier contraception and prevent bodily fluid transmission during and for 28 days after Ad5CMV-p53 gene administration

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

Not specified

Radiotherapy:

No concurrent intensity-modulated radiotherapy

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
2	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379