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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01111942
• Other study ID #: ROB-SCCI 10-001-1
• Status: Terminated
• Phase: Phase 0
• First received: April 26, 2010
• Last updated: August 4, 2015
• Start date: February 2010
• Est. completion date: January 2014

Study information

• Verified date: August 2015
• Source: Southern Illinois University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

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)

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.

Locations

Country	Name	City	State
United States	Southern Illinois University School of Medicine	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Southern Illinois University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Malone J, Robbins KT. Neck dissection after chemoradiation for carcinoma of the upper aerodigestive tract: indications and complications. Curr Opin Otolaryngol Head Neck Surg. 2010 Apr;18(2):89-94. doi: 10.1097/MOO.0b013e32833693e7. Review. — View Citation

Malone JP, Gerberi MA, Vasireddy S, Hughes LF, Rao K, Shevlin B, Kuhn M, Collette D, Tennenhouse J, Robbins KT. Early prediction of response to chemoradiotherapy for head and neck cancer: reliability of restaging with combined positron emission tomography and computed tomography. Arch Otolaryngol Head Neck Surg. 2009 Nov;135(11):1119-25. doi: 10.1001/archoto.2009.152. — View Citation

Robbins KT, Homma A. Intra-arterial chemotherapy for head and neck cancer: experiences from three continents. Surg Oncol Clin N Am. 2008 Oct;17(4):919-33, xi. doi: 10.1016/j.soc.2008.04.015. Review. — View Citation

Robbins KT, Howell SB, Williams JS. Intra-arterial chemotherapy for head and neck cancer: is there a verdict? Cancer. 2010 May 1;116(9):2068-70. doi: 10.1002/cncr.24930. — View Citation

Rogers LQ, Rao K, Malone J, Kandula P, Ronen O, Markwell SJ, Courneya KS, Robbins KT. Factors associated with quality of life in outpatients with head and neck cancer 6 months after diagnosis. Head Neck. 2009 Sep;31(9):1207-14. doi: 10.1002/hed.21084. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of pathologic complete response	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	No
Secondary	2 year overall survival	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	No
Secondary	Clinical complete response	To report the rate of clinical complete response of the local population following TPF induction chemotherapy	42 months	No
Secondary	2 year disease-free survival	To assess the 2 year disease-free survival of both subject groups	42 months	No
Secondary	Quality of life	Change in quality of life status at end of treatment, 1 year, and 2 year relative to baseline	42 months	No
Secondary	Incidence of HPV and EGFR positivity	To assess the incidence in both subject groups	42 months	No
Secondary	K-ras mutational analysis	To assess the incidence in both subject groups	42 months	No

External Links

•   SimmonsCooper Cancer Institute at SIU; clinical trials webpage