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Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

Primary Purpose

Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
paclitaxel
carboplatin
intensity-modulated radiation therapy
quality-of-life assessment
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Papilloma Virus Infection

Eligibility Criteria

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

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) 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 the following minimum diagnostic workup:

    • History/physical examination within 4 weeks prior to registration, including assessment of weight loss in past 6 months
    • Chest x-ray (or chest computed tomography [CT] scan or positron emission tomography [PET]/CT scan) within 6 weeks prior to registration
  • CT scan or magnetic resonance imaging (MRI) of the head and neck (of the primary tumor and neck nodes) and PET/CT scan
  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) > 1,800 cells/mm^3
  • Platelets > 100,000 cells/mm^3
  • Hemoglobin (Hgb) > 8.0 g/dl (note: the use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper limit of normal
  • Serum creatinine =< 1.5 mg/dl or institutional upper limit of normal
  • Creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
  • Negative serum pregnancy test within 7 days prior to start of induction chemotherapy (ICT) for women of childbearing potential
  • Women of childbearing potential and male participants are counseled on birth control and 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 have had initial surgical treatment other than the diagnostic biopsy of the primary site or nodal sampling of the neck disease are excluded
  • Patients with unknown primary tumor sites 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
  • Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction
  • Congestive heart failure with left ventricular ejection fraction < 20%
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Active lupus erythematosus or scleroderma with ongoing physical manifestations
  • Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
  • 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
  • Prior allergic reaction to the study drug(s) involved in this protocol
  • Patient is enrolled in another investigational trial

Sites / Locations

  • Jonsson Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (paclitaxel, carboplatin, IMRT)

Arm Description

INDUCTION: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients receive paclitaxel IV over 1 hour weekly and undergo IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression-free survival
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

Overall survival
Time to event distributions will be estimated using the Kaplan-Meier method.
Local-regional control
The 2-year rates of local-regional control will be calculated along with 95% CI for HPV-positive patients receiving the dose de-intensified therapy. It will also be compared with the rate from historical controls using a one-sided Z-test.
Incidence of mucosal and esophageal >= grade 3 toxicity graded according to the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0)
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, protocol treatment delivery (PTD) and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Incidence of other >= grade 3 toxicity graded according to NCI CTCAE v4.0
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
PTD
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Incidence of death
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Quality of life as assessed by Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) and University of Washington Quality of Life (UWQol)
Descriptive statistics for quality of life measurements will also be obtained, using mean and standard deviation for continuous measures and frequency tables for categorical measures.

Full Information

First Posted
January 27, 2014
Last Updated
August 10, 2018
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02048020
Brief Title
Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx 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
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 26, 2013 (Actual)
Primary Completion Date
January 9, 2017 (Actual)
Study Completion Date
January 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well paclitaxel and carboplatin before radiation therapy with paclitaxel works in treating human papillomavirus (HPV)-positive patients with stage III-IV oropharynx, hypopharynx, or larynx cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving paclitaxel and carboplatin before radiation therapy with paclitaxel may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the progression-free survival at 2 years in patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) who receive induction chemotherapy followed by dose de-intensified chemoradiotherapy. SECONDARY OBJECTIVES: I. To determine the overall survival and local-regional control for patients with HPV-positive HNSCC who receive induction chemotherapy and dose de-intensified chemoradiotherapy. II. To determine the incidence of acute grade 3+ mucosal and esophageal toxicity associated with attenuated concurrent chemoradiotherapy in patients with HPV-positive HNSCC. III. To determine the incidence of late toxicity in patients with HPV-positive HNSCC who receive the dose de-intensified chemoradiotherapy. IV. To estimate the incidence of all toxicity (hematologic and non-hematologic) associated with protocol treatment for all patients on trial. V. To estimate the response rate of HPV-positive to induction chemotherapy using carboplatin and paclitaxel. VI. To determine the effect of reduced radiation dose on short-term and long-term quality of life among patients treated by chemoradiotherapy. OUTLINE: INDUCTION: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients receive paclitaxel IV over 1 hour weekly and undergo intensity-modulated radiation therapy (IMRT) daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 3 months for 1 year, and then every 6 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Verrucous Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Verrucous Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Verrucous Carcinoma of the Larynx

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (paclitaxel, carboplatin, IMRT)
Arm Type
Experimental
Arm Description
INDUCTION: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients receive paclitaxel IV over 1 hour weekly and undergo IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
Undergo IMRT
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Progression-free survival
Description
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
From date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause, assessed at 2 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Time to event distributions will be estimated using the Kaplan-Meier method.
Time Frame
The time from registration to death, assessed up to 5 years
Title
Local-regional control
Description
The 2-year rates of local-regional control will be calculated along with 95% CI for HPV-positive patients receiving the dose de-intensified therapy. It will also be compared with the rate from historical controls using a one-sided Z-test.
Time Frame
2 years
Title
Incidence of mucosal and esophageal >= grade 3 toxicity graded according to the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0)
Description
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, protocol treatment delivery (PTD) and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time Frame
Up to 12 weeks after chemoradiotherapy
Title
Incidence of other >= grade 3 toxicity graded according to NCI CTCAE v4.0
Description
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time Frame
Up to 12 weeks after chemoradiotherapy
Title
PTD
Description
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time Frame
Up to 5 years
Title
Incidence of death
Description
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time Frame
During or within 30 days of discontinuation of protocol treatment
Title
Quality of life as assessed by Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) and University of Washington Quality of Life (UWQol)
Description
Descriptive statistics for quality of life measurements will also be obtained, using mean and standard deviation for continuous measures and frequency tables for categorical measures.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) 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 the following minimum diagnostic workup: History/physical examination within 4 weeks prior to registration, including assessment of weight loss in past 6 months Chest x-ray (or chest computed tomography [CT] scan or positron emission tomography [PET]/CT scan) within 6 weeks prior to registration CT scan or magnetic resonance imaging (MRI) of the head and neck (of the primary tumor and neck nodes) and PET/CT scan Zubrod performance status 0-1 Absolute neutrophil count (ANC) > 1,800 cells/mm^3 Platelets > 100,000 cells/mm^3 Hemoglobin (Hgb) > 8.0 g/dl (note: the use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper limit of normal Serum creatinine =< 1.5 mg/dl or institutional upper limit of normal Creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula Negative serum pregnancy test within 7 days prior to start of induction chemotherapy (ICT) for women of childbearing potential Women of childbearing potential and male participants are counseled on birth control and 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 have had initial surgical treatment other than the diagnostic biopsy of the primary site or nodal sampling of the neck disease are excluded Patients with unknown primary tumor sites 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 Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction Congestive heart failure with left ventricular ejection fraction < 20% Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Active lupus erythematosus or scleroderma with ongoing physical manifestations Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures 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 Prior allergic reaction to the study drug(s) involved in this protocol Patient is enrolled in another investigational trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allen Chen
Organizational Affiliation
Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
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
derived

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Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

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