A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer

August 4, 2015 updated by: Southern Illinois University
This is a non-randomized open-label investigator initiated pilot study comparing follow-up therapy of advanced head and neck cancer subjects initially treated with triple induction chemotherapy. Subjects will receive surgical treatment or combined chemoradiation therapy based on the subject's apparent clinical response. Spared use of radiation therapy for selective patients who have a complete response to induction chemotherapy could improve well being of this patient population without compromising survival.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

An important observation of the induction triple chemotherapy regimen know as TPF is that there was an unprecedented high proportion of patients treated who had a complete response of their disease upon the completion of the induction phase. In a recent study by Haddad, et al., a biopsy was performed in all patients following induction chemotherapy and before starting concomitant chemoradiotherapy. Patients with an incomplete response to chemoradiotherapy or who had N3 disease had a neck dissection 6 to 12 weeks after chemoradiotherapy. Twenty-nine neck dissections were performed after chemoradiotherapy. The neck dissection result was pathologically positive in 7 (24%) patients (all alive with no evidence of disease) and negative in 22 (76%) patients (21 alive with no evidence of disease). Post-TPF, primary site biopsy result was negative in 64 patients (89%) and positive in 8 patients (11%). While the protocol required all patients to subsequently receive concomitant chemoradiation regardless of disease response to the induction component of the regimen, it is reasonable to question whether the complete responder subset really needed to undergo the same intensive chemoradiation treatment compared to the partial responders. Thus, a less intense therapy may be sufficient. The long term goal of this protocol is to alter the model of highly effective cancer therapy from what is maximally tolerated by the patient to what is minimally necessary for a cure.

One treatment strategy for patients with advanced head and neck cancer who prove to be highly sensitive to chemotherapy is to combine the modalities of polychemotherapy and conservation surgery with the goal of avoiding radiation therapy. For those patients whose primary disease is classified as T2-3 (resectable), and who have a complete response following induction therapy, it is feasible to perform an organ preservation tumor nidusectomy at the primary site to verify that the clinical complete response is truly pathological complete response. Similarly, the clinical complete response observed for the associated nodal disease, can be verified pathologically by performing a selective neck dissection without causing significant morbidity. Both tumor nidusectomy and selective neck dissection has been shown to be an effective adjuvant in this setting. Building on these observations, the novel protocol outlined in this proposal has the potential to spare the use of radiation therapy for selective patients who have a complete response to induction chemotherapy and thereby improve their well being without compromising survival.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Springfield, Illinois, United States, 62701
        • Southern Illinois University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Ability to understand and the willingness to sign a written informed consent document.
  2. Histologically confirmed Stage III-IV (T1, T2, T3) (N0-N2) squamous cell carcinoma of the oropharynx staged according to AJCC guidelines.
  3. The subject must be considered surgically resectable via a transoral approach at the time of presentation.
  4. Age >18 years
  5. Life expectancy >/= 5 years
  6. ECOG performance status <2
  7. Subject must have measurable disease, at least one lesion accurately measured in at least one dimension as >10 mm with CT scan.
  8. Hematologic Absolute neutrophil count > 1,000/mm3, Hemoglobin > 8.0 g/dl Platelet count > 100,000/mm3 Leukocytes >3,000/mcL
  9. Hepatic Total Bilirubin ≤ ULN; AST and ALT and Alkaline Phosphatase within the eligible range
  10. Renal - creatinine within normal institutional limits or >60 mL/min/1.73 m2 creatinine > institutional normal
  11. Women of childbearing potential with negative pregnancy test.
  12. Men and women of childbearing age willing to use effective contraception

Exclusion Criteria:

  1. N3 nodal disease according to AJCC guidelines
  2. Retropharyngeal nodal involvement
  3. Trismus
  4. Second primary head and neck tumor unless it is/was a basal or squamous cell skin cancer
  5. Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy
  6. Concurrent investigational agent or intervention (within 90 days of screening visit)
  7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxol, cisplatin, 5- fluorouracil, or carboplatin.
  8. History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
  9. Breastfeeding women
  10. Pre-existing peripheral neuropathy grade > 3
  11. Evidence of distant metastatic disease
  12. Unknown primary site
  13. Prior or concurrent malignancies (excluding adequately treated basal or squamous cell skin cancer, in situ cervical cancer, stage I or II cancer from which the subject has been in complete remission for at least 12 months (excluding head and neck), any cancer from which the subject has been cancer free for 5 years)
  14. History of allergies to any of the pre-medications.
  15. Investigator consideration based upon screening interview and/or procedures
  16. Evidence of bone invasion/destruction
  17. Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  18. Pregnant women
  19. History of HIV, hepatitis B, hepatitis C, or delta antigen
  20. Known allergy to India Ink or methylene blue

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: radiation and weekly carboplatin
Other: radiation combined with weekly carboplatin

recommended premedications: Aloxi 0.25 mg IV; Dexamethasone 20 mg IV; Fosaprepitant 115 mg IV; Aprepitant 80 mg PO; Ativan 1.0 mg IV;

Mucositis treatment should involve local measures to maintain oral hygiene, oral nystatin or fluconazole, or valacyclovir for viral infection.

Induction Triple Therapy Treatment with TPF:

Docetaxel (Taxotere) 75 mg/m2 IV; Cisplatin (Platinol) 100 mg/m2 IV; 1500 cc Normal Saline w/20meq KCL, 1 gram MgSo4 IV; 5-Fluorouracil (Adrucil) 1000 mg/m2 day IV-continuous infusion over 4 days; Neulasta* 6 mg SC Day 5 (*Neupogen may be substituted at the investigator's discretion)

Other Names:
  • Taxotere
  • Platinol
  • Cisplatin
  • 5-Fluorouracil
  • Adrucil
  • Docetaxel
Other: conservation surgery
Procedure: conservation surgery
Following induction triple chemotherapy, subjects will be restaged by physical examination and radiological imaging. If there is an absence of unequivocal evidence for residual disease (i.e. an apparent complete response), the subject will undergo conservation surgery under general anesthesia, using a transoral approach. Minimal tissue removal through direct access. The surgical specimen will be evaluated by a pathologist in the manner standard for the institution. The presence of residual tumor will be classified as a partial response to induction triple chemotherapy and the subject will undergo concomitant chemoradiotherapy. If there is no evidence of residual disease in the surgical specimen, the subject will be followed for recurrence.
Other Names:
  • Taxotere
  • Platinol
  • Cisplatin
  • 5-Fluorouracil
  • Adrucil
  • Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of pathologic complete response
Time Frame: 42 months
To assess the rate of pathologic complete response of subjects (based on analysis of the surgical specimen), in both the primary site as well as the lymph nodes, with resectable stage III-IV squamous cell carcinoma of the oropharynx treated with TPF induction chemotherapy followed by conservation (organ preservation) surgery for clinically complete responders
42 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2 year overall survival
Time Frame: 42 months
To assess the 2 year overall survival of subjects with resectable stage III-IV squamous cell carcinoma of the oropharynx treated with TPF induction chemotherapy followed by chemoradiation for clinically incomplete responders.
42 months
Clinical complete response
Time Frame: 42 months
To report the rate of clinical complete response of the local population following TPF induction chemotherapy
42 months
2 year disease-free survival
Time Frame: 42 months
To assess the 2 year disease-free survival of both subject groups
42 months
Quality of life
Time Frame: 42 months
Change in quality of life status at end of treatment, 1 year, and 2 year relative to baseline
42 months
Incidence of HPV and EGFR positivity
Time Frame: 42 months
To assess the incidence in both subject groups
42 months
K-ras mutational analysis
Time Frame: 42 months
To assess the incidence in both subject groups
42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southern Illinois University

Investigators

  • Principal Investigator: K. T. Robbins, M.D., Southern Illinois University School of Medicine
  • Principal Investigator: Krishna Rao, M.D., Ph.D., Southern Illinois University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

April 26, 2010

First Submitted That Met QC Criteria

April 26, 2010

First Posted (Estimate)

April 28, 2010

Study Record Updates

Last Update Posted (Estimate)

August 5, 2015

Last Update Submitted That Met QC Criteria

August 4, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ROB-SCCI 10-001-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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