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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Southern Illinois University
Sponsor:
Information provided by (Responsible Party):
Southern Illinois University
ClinicalTrials.gov Identifier:
NCT01111942
First received: April 26, 2010
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Other: radiation combined with weekly carboplatin
Procedure: conservation surgery
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Southern Illinois University:

Primary Outcome Measures:
  • Rate of pathologic complete response [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 2 year overall survival [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    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.

  • Clinical complete response [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    To report the rate of clinical complete response of the local population following TPF induction chemotherapy

  • 2 year disease-free survival [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    To assess the 2 year disease-free survival of both subject groups

  • Quality of life [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    Change in quality of life status at end of treatment, 1 year, and 2 year relative to baseline

  • Incidence of HPV and EGFR positivity [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    To assess the incidence in both subject groups

  • K-ras mutational analysis [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    To assess the incidence in both subject groups


Estimated Enrollment: 10
Study Start Date: February 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Docetaxel
  • Taxotere
  • Cisplatin
  • Platinol
  • 5-Fluorouracil
  • Adrucil
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:
  • Docetaxel
  • Taxotere
  • Cisplatin
  • Platinol
  • 5-Fluorouracil
  • Adrucil

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111942

Contacts
Contact: K. T. Robbins,, M.D. 217-545-6818 trobbins@siumed.edu
Contact: Kathy Robinson, Ph.D. 217-545-1946 krobinson@siumed.edu

Locations
United States, Illinois
Southern Illinois University School of Medicine Recruiting
Springfield, Illinois, United States, 62701
Principal Investigator: K. T. Robbins, M.D.         
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications:
Responsible Party: Southern Illinois University
ClinicalTrials.gov Identifier: NCT01111942     History of Changes
Other Study ID Numbers: ROB-SCCI 10-001-1
Study First Received: April 26, 2010
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Southern Illinois University:
head and neck cancer
chemotherapy
radiation

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Docetaxel
Cisplatin
Fluorouracil
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 20, 2014