Porfiromycin Used as an Adjuvant to Radiation Therapy in Postoperative Head and Neck Cancer Patients

A Phase III, Double-Blind, Randomized, Placebo-Controlled Study of Porfiromycin Used as an Adjuvant to Radiation Therapy in Postoperative Head and Neck Cancer Patients

Determination of efficacy and safety of porfiromycin versus placebo as an adjuvant to radiotherapy in postoperative head and neck a cancer patients as well as assessment of population pharmacokinetic parameters.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: Placebo; Radiation: Radiotherapy; Drug: Porfiromycin

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female postoperative radical neck surgery patients with histologically proven Stage III or IV (without distant metastases) epidermoid (squamous cell) carcinoma of the head and neck limited to the following locations as defined by the American Joint Commission (AJC): lip and oral cavity, pharynx, or larynx.
• Postoperative radical patients whose specimen had a) microscopic positive tumor cell margins (< 2mm from surgical margin) or b) extranodal capsular spread (perineural-vascular embolization) or c) two or more positive nodes
• Postoperative radical neck patients must have received Radiotherapy (RT).
• Performance status of ≥ 70 on the Karnofsky Performance Score (KPS) at screening.
• Patients ≥ 18 years of age
• Patients must have provided written informed consent prior to participation in the trial.
• Patients must have demonstrated an educational level and a degree of understanding such that they could communicate effectively with the investigator.

Exclusion Criteria:

• Patients that received any prior chemotherapy including mitomycin-C or porfiromycin.
• Treatment with granulocyte, granulocyte-macrophage stimulating factor (G-CSF, GM-CSF) or Interleukin-11 within 30 days prior to start of RT.
• RT within the treatment field for any malignancy within the past five years.
• Patients who had any gross (visible or palpable) residual disease left after surgery.

• Patients who met any of the following clinical laboratory criteria upon screening:

  1. Granulocyte (neutrophil) count of < 1,500/cubic millimeters (mm3)
  2. Platelets < 75,000/mm3
  3. Prothrombin time (PT) and partial thromboplastin time (PTT) > 1.5 times the upper limit of normal (ULN) in seconds.
• Women who were pregnant or nursing.
• Women of childbearing potential who were unwilling to utilise a medically acceptable method of contraception (oral contraceptives, intrauterine devices, diaphragm or subdermal implants eg: Norplant®).
• Other malignancies active within the past five years (other than basal or squamous cell carcinomas of the skin outside the planned radiation portals, or in situ carcinoma of the cervix).
• The presence of more than one primary tumor or presence of distant metastases.
• The presence of any other life-threatening illness, such a severe chronic lung, liver, or heart disease that would be expected to be fatal within five years, regardless of the patient's cancer status.
• Patients who participated in a clinical trial with another investigational drug or treatment 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Porfiromycin + Radiotherapy	Radiation: Radiotherapy; Drug: Porfiromycin
Placebo Comparator: Placebo + Radiotherapy	Drug: Placebo; Radiation: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Disease Progression	week 4 and 8 post treatment, every 8 weeks until end of study
Maximum toxicity grades of Adverse Events (AE)	until 42 days after end of treatment
Time to non-accidental death	week 4 and 8 post treatment, every 8 weeks until end of study
Serum porfiromycin concentration-time profile	up to week 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Death for any reason	4 weeks post treatment for every 8 weeks through 48 weeks, every 12 weeks until end of study
Loss of local or regional control, distant metastasis or death for any reason	4 weeks post treatment for every 8 weeks through 48 weeks, every 12 weeks until end of study
Loss of local or regional control or distant metastasis	4 weeks post treatment for every 8 weeks through 48 weeks, every 12 weeks until end of study
Loss of local or regional control	4 weeks post treatment for every 8 weeks through 48 weeks, every 12 weeks until end of study
Occurrence of Adverse Events	up to week 16
Significant changes in laboratory tests	up to week 7
Changes from baseline in Patients health related Quality of life-Questionnaires	week 1, 5, 7, 4 weeks post treatment, every 12 weeks until end of study

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): December 1, 2000

Study Registration Dates

• First Submitted: July 4, 2014
• First Submitted That Met QC Criteria: July 4, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 4, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antibiotics, Antineoplastic; Porfiromycin
• Other Study ID Numbers: 1164.4