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

NCT ID: NCT00017173

Last Updated: 2012-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2011-07-31

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.

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Ad5CMV-p53 gene

Intervention Type: BIOLOGICAL

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

cisplatin

Intervention Type: DRUG

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

conventional surgery

Intervention Type: PROCEDURE

conventional surgery

radiation therapy

Intervention Type: RADIATION

200 cGy per day Days 105 every week for 6 weeks

Interventions

Ad5CMV-p53 gene

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

Intervention Type: BIOLOGICAL

cisplatin

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

Intervention Type: DRUG

conventional surgery

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

200 cGy per day Days 105 every week for 6 weeks

Intervention Type: RADIATION

Other Intervention Names

INGN 201; platinol; surgery; RT

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George H. Yoo, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

References

Yoo GH, Moon J, Leblanc M, Lonardo F, Urba S, Kim H, Hanna E, Tsue T, Valentino J, Ensley J, Wolf G. A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p53) gene therapy followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx: report of the Southwest Oncology Group. Arch Otolaryngol Head Neck Surg. 2009 Sep;135(9):869-74. doi: 10.1001/archoto.2009.122.

Reference Type: DERIVED

PMID: 19770418 (View on PubMed)

Other Identifiers

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0011

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000068658

Identifier Type: -

Identifier Source: org_study_id