A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer
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|ClinicalTrials.gov Identifier: NCT01111942|
Recruitment Status : Terminated (lack of enrollment)
First Posted : April 28, 2010
Last Update Posted : August 5, 2015
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer||Other: radiation combined with weekly carboplatin Procedure: conservation surgery||Early Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer|
|Study Start Date :||February 2010|
|Actual Primary Completion Date :||January 2014|
|Actual Study Completion Date :||January 2014|
|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)
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.
- 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
- 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.
- Clinical complete response [ Time Frame: 42 months ]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 ]To assess the 2 year disease-free survival of both subject groups
- 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
- Incidence of HPV and EGFR positivity [ Time Frame: 42 months ]To assess the incidence in both subject groups
- K-ras mutational analysis [ Time Frame: 42 months ]To assess the incidence in both subject groups
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01111942
|United States, Illinois|
|Southern Illinois University School of Medicine|
|Springfield, Illinois, United States, 62701|
|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|