Clinical trial NCT00017173: S0011, Gene Therapy & Surgery Followed by Chemo & RT in Newly Diagnosed Cancer of the Mouth or Throat
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: 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 III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV verrucous carcinoma of the larynx
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Feasibility
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival from time of registration until disease progression
timeFrame: two years
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: George H. Yoo, MD
role: STUDY_CHAIR
References:
citation: 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.