RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known if treatment with cisplatin plus epinephrine is effective for head and neck cancer.

PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of cisplatin plus epinephrine in injectable gel form in treating patients who have recurrent or refractory head and neck cancer.

Condition	Treatment or Intervention	Phase
recurrent squamous cell carcinoma of the hypopharynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity recurrent squamous cell carcinoma of the oropharynx recurrent squamous cell carcinoma of the nasopharynx recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity	Drug: cisplatin  Drug: cisplatin-e therapeutic implant  Drug: epinephrine  Drug: placebo	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the effect of intratumoral injection of a cisplatin/epinephrine gel (CDDP-e TI) to placebo gel for local control of recurrent or refractory squamous cell carcinoma of the head and neck.

II. Assess achievement of a preselected (by the investigator) treatment goal for the most troublesome tumor in patients with recurrent or refractory squamous cell carcinoma of the head and neck following up to 6 weekly intratumoral treatments with CDDP-e TI vs. placebo gel.

III. Compare the effect of CDDP-e TI to placebo gel on total local tumor volume per patient.

IV. Evaluate the time to response and time to progression for the most troublesome tumor after local treatment with CDDP-e TI vs. placebo gel.

V. Assess the improvement in or stabilization of quality of life in these patients as measured by the FACT-H&N questionnaire.

VI. Compare the histopathology of injected lesions that respond to local treatment.

PROTOCOL OUTLINE: Randomized, double-blind study. Randomization weighted 2:1 in favor of Arm I.

Arm I: Intratumoral Chemotherapy. Cisplatin (NSC-119875) and Epinephrine in a bovine collagen gel, MP 5010, CDDP-e TI.

Arm II: Control. NS in a bovine collagen gel, PLCB.

PROJECTED ACCRUAL: Up to 120 evaluable patients will be studied to provide 80 evaluable patients on Arm I and 40 evaluable patients on Arm II.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed squamous cell carcinoma of the head and neck that is recurrent or refractory following at least 1 course of therapy; Primary or metastatic tumors involving skin, nodes (palpable and biopsy- proven), subcutaneous tissue, or muscle allowed; No involvement of major artery or any visceral organ; Measurable lesions accessible for direct intratumoral injection with no immediate risk of hemorrhage or embolization; Most troublesome tumor (identified by the investigator) at least 0.5 cc and no greater than 20 cc; Smaller tumors eligible for treatment but not for efficacy assessment
• An improvable primary treatment goal (palliative or preventive) for most troublesome tumor must be identified by the investigator prior to enrollment; If multiple tumors qualify as most troublesome and share the primary physician-selected treatment goal, the largest tumor is selected; Patient may also select a most troublesome tumor and 1 palliative treatment goal for that tumor (need not match the physician-selected tumor or goal)
• No fibrotic lesions (e.g., previously irradiated lesion with no subsequent disease progression)
• No tumors involving or threatening to invade the carotid or other major vessel

--Prior/Concurrent Therapy--

• More than 28 days since any antineoplastic therapy or therapy with investigational agents
• Fully recovered from side effects of prior treatment

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60%-100%
• Life expectancy: At least 6 months
• Hematopoietic: Absolute granulocyte count greater than 1,000/mm3; Platelet count greater than 75,000/mm3
• Hepatic: Not specified
• Renal: Creatinine no greater than 1.5 times normal
• Cardiovascular: No NYHA class III/IV status; No history of arrhythmia that would increase risk of treatment
• Other: No hypersensitivity to cisplatin, bovine collagen, epinephrine, or sulfites; No significant history of extracranial carotid vascular disease from atherosclerosis, radiation therapy or previous carotid artery surgery; No uncontrolled local infection at treatment sites; No medical or psychiatric condition that would preclude informed consent; No pregnant or nursing women; Adequate contraception required of fertile patients

Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
      Veterans Affairs Medical Center - Palo Alto, Palo Alto,  California,  94304,  United States
Florida
      Comprehensive Cancer Center at JFK Medical Center, Atlantis,  Florida,  33462,  United States
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
Illinois
      Evanston Northwestern Health Care, Evanston,  Illinois,  60201,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Kentucky
      University of Kentucky College of Medicine, Lexington,  Kentucky,  40536-0084,  United States
Louisiana
      Louisiana State University Hospital - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      Louisiana State University Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
Maryland
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21218,  United States
Missouri
      Capitol Comprehensive Cancer Care Clinic, Jefferson City,  Missouri,  65109,  United States
      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States
Nebraska
      Creighton University Cancer Center, Omaha,  Nebraska,  68131-2197,  United States
      Methodist Cancer Center - Omaha, Omaha,  Nebraska,  68114,  United States
New Mexico
      University of New Mexico Cancer Research & Treatment Center, Albuquerque,  New Mexico,  87131,  United States
Oregon
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
South Carolina
      Palmetto Richland Memorial Hospital, Columbia,  South Carolina,  29203,  United States
Tennessee
      Boston Cancer Group, Memphis,  Tennessee,  38119,  United States
      Thompson Cancer Survival Center, Knoxville,  Tennessee,  37916,  United States
Texas
      Southwest Regional Cancer Center, Austin,  Texas,  78705,  United States
      University of Texas Southwestern Medical School, Dallas,  Texas,  75235-9032,  United States
Wisconsin
      Department of Otolaryngology, Milwaukee,  Wisconsin,  53226,  United States
Canada, Quebec
      Montreal General Hospital, Montreal,  Quebec,  H3G 1A4,  Canada
      Ville Marie Oncology Center, Montreal,  Quebec,  H3G 1L5,  Canada

Study chairs or principal investigators

Mack H. Mabry,  Study Chair,  Matrix Pharmaceutical   

Study ID Numbers:  CDR0000064225; MP-414-94-2; NCI-V95-0676
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002659
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08