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Induction Chemotherapy Followed by Chemoradiotherapy for Head and Neck Cancer

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Induction Chemotherapy followed by Response Adapted Chemoradiation
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Human Papillomavirus, HPV

Eligibility Criteria

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

Inclusion Criteria:

  • Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. HPV-positivity will be defined as tumors that are p16-positive by immunohistochemistry.
  • Clinical stage III or IV disease; Note: Patients with M1 tumors are not eligible.
  • Appropriate stage for protocol entry, including no distant metastases, based upon minimum diagnostic workup
  • Zubrod Performance Status 0-1
  • Age > 18
  • Adequate bone marrow function
  • Adequate hepatic function
  • Adequate renal function
  • Pregnancy test within 4 weeks prior to registration for women of childbearing potential
  • Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
  • Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;
  • Patients with simultaneous primaries or bilateral tumors are excluded.
  • Patients who present with a cervical lymph node metastasis of unknown primary origin;
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
  • Prior radiotherapy that would result in overlap of radiation therapy fields;
  • Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or salivary glands;
  • Recurrent head and neck cancer;
  • Severe, active co-morbidity
  • Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • Prior allergic reaction to the study drug(s) involved in this protocol.

Sites / Locations

  • University of California Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Response Adapted Chemoradiation

Arm Description

Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel

Outcomes

Primary Outcome Measures

Number of Participants With Progression-free Survival
Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.

Secondary Outcome Measures

Number of Participants With Overall Survival
Defined as the time from registration to death using the Kaplan-Meier method..
Number of Patients With Toxicity of Concurrent Chemoradiotherapy
Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.

Full Information

First Posted
October 25, 2012
Last Updated
February 24, 2021
Sponsor
University of California, Davis
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1. Study Identification

Unique Protocol Identification Number
NCT01716195
Brief Title
Induction Chemotherapy Followed by Chemoradiotherapy for Head and Neck Cancer
Official Title
Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
March 8, 2017 (Actual)
Study Completion Date
October 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether human papillomavirus (HPV)-positive head and neck cancer can be treated with a less aggressive regimen of radiation therapy and chemotherapy (paclitaxel) after initially receiving two cycles of chemotherapy (carboplatin/paclitaxel).
Detailed Description
Given the toxicity of high dose cisplatin, attention has focused on identifying patients at lower risk for failure who may potentially benefit from less aggressive chemoradiotherapy approaches. HPV-positive Head and Neck Cancer responds favorably to radiation therapy. This has prompted investigators to suggest that patients with these cancers might be "over-treated" and unnecessarily subjected to the toxicity of intensive chemoradiotherapy with excessively high radiation doses. This study will select patients with HPV-positive Head and Neck cancer for attenuated therapy and may have important implications for individualization of care in the future. The regimen of carboplatin and paclitaxel was selected for the induction chemotherapy phase because of its ease of administration, improved toxicity profile, high rates of dose delivery, and excellent published results showing high response rates and overall survival. This study will use induction chemotherapy primarily as a means to select HPV-positive Head and Neck Cancer patients, who may benefit from significant radiation dose de-intensification in the concurrent chemoradiotherapy phase of treatment. The rationale for this risk-adapted approach to local therapy based on HPV status is to administer effective comprehensive treatment individualized at diagnosis and after assessment of response to induction chemotherapy (for patients with HPV-positive tumors), thus avoiding unnecessary and potentially toxic treatment, and hence optimizing the therapeutic ratio.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Human Papillomavirus, HPV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Response Adapted Chemoradiation
Arm Type
Experimental
Arm Description
Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel
Intervention Type
Radiation
Intervention Name(s)
Induction Chemotherapy followed by Response Adapted Chemoradiation
Other Intervention Name(s)
Paclitaxel, Carboplatin
Intervention Description
All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.
Primary Outcome Measure Information:
Title
Number of Participants With Progression-free Survival
Description
Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Number of Participants With Overall Survival
Description
Defined as the time from registration to death using the Kaplan-Meier method..
Time Frame
Up to 5 years
Title
Number of Patients With Toxicity of Concurrent Chemoradiotherapy
Description
Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. HPV-positivity will be defined as tumors that are p16-positive by immunohistochemistry. Clinical stage III or IV disease; Note: Patients with M1 tumors are not eligible. Appropriate stage for protocol entry, including no distant metastases, based upon minimum diagnostic workup Zubrod Performance Status 0-1 Age > 18 Adequate bone marrow function Adequate hepatic function Adequate renal function Pregnancy test within 4 weeks prior to registration for women of childbearing potential Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment) Patient must sign study specific informed consent prior to study entry. Exclusion Criteria: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; Patients with simultaneous primaries or bilateral tumors are excluded. Patients who present with a cervical lymph node metastasis of unknown primary origin; Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; Prior radiotherapy that would result in overlap of radiation therapy fields; Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or salivary glands; Recurrent head and neck cancer; Severe, active co-morbidity Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Prior allergic reaction to the study drug(s) involved in this protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Megan Daly, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28434660
Citation
Chen AM, Felix C, Wang PC, Hsu S, Basehart V, Garst J, Beron P, Wong D, Rosove MH, Rao S, Melanson H, Kim E, Palmer D, Qi L, Kelly K, Steinberg ML, Kupelian PA, Daly ME. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol. 2017 Jun;18(6):803-811. doi: 10.1016/S1470-2045(17)30246-2. Epub 2017 Apr 20.
Results Reference
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Induction Chemotherapy Followed by Chemoradiotherapy for Head and Neck Cancer

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