Back to results

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

Primary Purpose

Head and Neck Cancer

Status

Terminated

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

radiation combined with weekly carboplatin

conservation surgery

About this trial

This is an interventional diagnostic trial for Head and Neck Cancer focused on measuring head and neck cancer, chemotherapy, radiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

N3 nodal disease according to AJCC guidelines
Retropharyngeal nodal involvement
Trismus
Second primary head and neck tumor unless it is/was a basal or squamous cell skin cancer
Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy
Concurrent investigational agent or intervention (within 90 days of screening visit)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxol, cisplatin, 5- fluorouracil, or carboplatin.
History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
Breastfeeding women
Pre-existing peripheral neuropathy grade > 3
Evidence of distant metastatic disease
Unknown primary site
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)
History of allergies to any of the pre-medications.
Investigator consideration based upon screening interview and/or procedures
Evidence of bone invasion/destruction
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
Pregnant women
History of HIV, hepatitis B, hepatitis C, or delta antigen
Known allergy to India Ink or methylene blue

Sites / Locations

Southern Illinois University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

radiation and weekly carboplatin

conservation surgery

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Clinical complete response

To report the rate of clinical complete response of the local population following TPF induction chemotherapy

2 year disease-free survival

To assess the 2 year disease-free survival of both subject groups

Quality of life

Change in quality of life status at end of treatment, 1 year, and 2 year relative to baseline

Incidence of HPV and EGFR positivity

To assess the incidence in both subject groups

K-ras mutational analysis

To assess the incidence in both subject groups

Full Information

NCT ID

NCT01111942

First Posted

April 26, 2010

Last Updated

August 4, 2015

Sponsor

Southern Illinois University

1. Study Identification

Unique Protocol Identification Number

NCT01111942

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Terminated

Why Stopped

lack of enrollment

Study Start Date

February 2010 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Southern Illinois University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer

Keywords

head and neck cancer, chemotherapy, radiation

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

radiation and weekly carboplatin

Arm Type

Active Comparator

Arm Title

conservation surgery

Arm Type

Other

Intervention Type

Other

Intervention Name(s)

radiation combined with weekly carboplatin

Other Intervention Name(s)

Docetaxel, Taxotere, Cisplatin, Platinol, 5-Fluorouracil, Adrucil

Intervention Description

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)

Intervention Type

Procedure

Intervention Name(s)

conservation surgery

Other Intervention Name(s)

Docetaxel, Taxotere, Cisplatin, Platinol, 5-Fluorouracil, Adrucil

Intervention Description

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.

Primary Outcome Measure Information:

Title

Rate of pathologic complete response

Description

Time Frame

42 months

Secondary Outcome Measure Information:

Title

2 year overall survival

Description

Time Frame

42 months

Title

Clinical complete response

Description

To report the rate of clinical complete response of the local population following TPF induction chemotherapy

Time Frame

42 months

Title

2 year disease-free survival

Description

To assess the 2 year disease-free survival of both subject groups

Time Frame

42 months

Title

Quality of life

Description

Change in quality of life status at end of treatment, 1 year, and 2 year relative to baseline

Time Frame

42 months

Title

Incidence of HPV and EGFR positivity

Description

To assess the incidence in both subject groups

Time Frame

42 months

Title

K-ras mutational analysis

Description

To assess the incidence in both subject groups

Time Frame

42 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document. Histologically confirmed Stage III-IV (T1, T2, T3) (N0-N2) squamous cell carcinoma of the oropharynx staged according to AJCC guidelines. The subject must be considered surgically resectable via a transoral approach at the time of presentation. Age >18 years Life expectancy >/= 5 years ECOG performance status <2 Subject must have measurable disease, at least one lesion accurately measured in at least one dimension as >10 mm with CT scan. Hematologic Absolute neutrophil count > 1,000/mm3, Hemoglobin > 8.0 g/dl Platelet count > 100,000/mm3 Leukocytes >3,000/mcL Hepatic Total Bilirubin ≤ ULN; AST and ALT and Alkaline Phosphatase within the eligible range Renal - creatinine within normal institutional limits or >60 mL/min/1.73 m2 creatinine > institutional normal Women of childbearing potential with negative pregnancy test. Men and women of childbearing age willing to use effective contraception Exclusion Criteria: N3 nodal disease according to AJCC guidelines Retropharyngeal nodal involvement Trismus Second primary head and neck tumor unless it is/was a basal or squamous cell skin cancer Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy Concurrent investigational agent or intervention (within 90 days of screening visit) History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxol, cisplatin, 5- fluorouracil, or carboplatin. History of severe hypersensitivity reaction to drugs formulated with polysorbate 80 Breastfeeding women Pre-existing peripheral neuropathy grade > 3 Evidence of distant metastatic disease Unknown primary site 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) History of allergies to any of the pre-medications. Investigator consideration based upon screening interview and/or procedures Evidence of bone invasion/destruction 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 Pregnant women History of HIV, hepatitis B, hepatitis C, or delta antigen Known allergy to India Ink or methylene blue

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

K. T. Robbins, M.D.

Organizational Affiliation

Southern Illinois University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Krishna Rao, M.D., Ph.D.

Organizational Affiliation

Southern Illinois University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Southern Illinois University School of Medicine

City

Springfield

State/Province

Illinois

ZIP/Postal Code

62701

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20186833

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. No abstract available.

Results Reference

background

PubMed Identifier

20125024

Citation

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.

Results Reference

background

PubMed Identifier

19917925

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.

Results Reference

background

PubMed Identifier

19360748

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.

Results Reference

background

PubMed Identifier

18722926

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs