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Pilot Study of Chemotherapy for HPV-Associated Oropharyngeal Cancer

Primary Purpose

Oropharyngeal Squamous Cell Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Transoral Robotic Surgery (TORS) or Radiotherapy
Chemotherapy and Low-Dose Radiotherapy
Chemotherapy and High-Dose Radiotherapy
Paclitaxel
Carboplatin
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Oropharyngeal Squamous Cell Carcinoma focused on measuring Oropharyngeal squamous cell carcinoma, head and neck cancer, HPV, human papillomavirus, OPSCC

Eligibility Criteria

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

Inclusion Criteria:

  1. Subjects must have clinically confirmed Human papillomavirus(HPV)-positive head and neck squamous cell cancer of the back of the mouth/throat (oropharynx). Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
  2. HPV testing must be compliant with the following criteria:

    1. P16INK4a immunohistochemistry (p16 IHC) positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al72).
    2. p16 IHC positivity is to be validated using an HPV Polymerase chain reaction (PCR - a type of DNA copying method).
    3. HPV PCR must demonstrate HPV16 or HPV18 subtype
  3. Availability of greater than 10 unstained 5 micron slides (to be provided to HTRC at the University of Chicago). Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
  4. Participants must be at least 18 years old.
  5. Participants with American Joint Committee on Cancer (AJCC) (8th edition, 2018) N1 (>=3cm), N2-N3 nodal disease or T3-T4 primary tumor.
  6. Measurable disease (either primary site or nodal disease) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
  7. No previous radiation or chemotherapy for a head and neck cancer.
  8. No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or biopsies will occur after baseline scans are performed and measurable lesions are identified.
  9. Eastern Cooperate Oncology Group performance status 0-1
  10. Normal organ function clinically confirmed by medical records.
  11. Participants must sign a study-specific informed consent form prior to study entry. Participants should have the ability to understand and the willingness to sign a written informed consent document.
  12. Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
  13. Women must not be breastfeeding.
  14. Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment.
  15. Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s).

Exclusion Criteria:

  1. Any sign of metastatic disease (M1 disease).
  2. Non-HPV16/18 subtype
  3. Unidentifiable primary site of cancer.
  4. Other medical illnesses that may impair the participant's ability to receive therapy or limit survival. This includes but is not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible (conditions to be reviewed by the PI to confirm eligibility)
  5. Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above.
  6. Patients receiving other investigational agents.
  7. Prior systemic anti-cancer treatment within the last 8 weeks.
  8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment.
  9. Has known history of, or any evidence of active, non-infectious pneumonitis.
  10. Has a history of HIV.
  11. Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible.
  12. Has received a live vaccine within 28 days of planned start of study therapy.

Sites / Locations

  • University of Chicago Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group A - Low Risk

Group B - Intermediate Risk

Group C - High-Risk

Induction Therapy (Carboplatin and Paclitaxel)

Arm Description

Participants who have low-risk cancer and significant reduction (greater than 50%) in tumor size following induction therapy will be assigned to this group.

Participants who have low-risk cancer and intermediate reduction (30-50%) in tumor size or high-risk cancer with significant reduction (greater than or equal to 50%) in tumor size following induction therapy will be assigned to this group.

Participants who have high-risk cancer and less than a 50% reduction in their tumor size following induction therapy will be assigned to this group.

All study participants will be assigned to this group to first receive induction therapy using a combination of carboplatin and paclitaxel. Participant response to this phase of therapy will determine which group (low-risk, intermediate risk or high-risk) the participant will be in.

Outcomes

Primary Outcome Measures

Feasibility of collection of serial HPV-DNA blood samples in patients undergoing treatment for Oropharyngeal Squamous Cell Carcinoma
To determine if it is possible (feasibility) to measure HPV-DNA using blood tests among participants undergoing induction chemotherapy followed by a second round of response-based therapy for their HPV-associated cancer. This feasibility will be determined by measuring the proportion of patients who complete chemotherapy treatment and HPV-DNA assessments.
Relationship Between HPV-DNA Found in Participant's Blood and Participant Response to Chemotherapy
To evaluate the relationship (aka correlation) between the amount of HPV-DNA found in a participant's plasma/blood and the participant's response to induction chemotherapy based on how their tumor responds to treatment.

Secondary Outcome Measures

Changes in Blood Containing HPV-DNA During Response-Based Therapy
To evaluate changes in blood containing HPV-DNA during a second round of chemotherapy (known as response-based chemo-radiotherapy) that will be based on how the participant responded to their first/induction phase of chemotherapy treatment. This outcome will be measured by checking quantitative HPV DNA in plasma with each cycle of induction chemotherapy, weekly during radiation treatment, and following completion of radiation at set time points within the study.
Side Effects of Cisplatin-Based Chemotherapy Treatment
To evaluate the side effects of weekly cisplatin-based treatment in participants receiving chemotherapy followed by a second round of response-based therapy for their HPV-associated cancer.
Tumor Response Among Participants Undergoing Transoral Robotic Surgery
To determine how participant's tumor/cancer responds when they are undergoing Transoral Robotic Surgery (TORS) following induction chemotherapy. TORs is surgery in which a robot with arms is used to remove cancer from hard-to-reach areas of the mouth and throat. Data about how patients' tumors respond in this study will be compared to similar data from a previous study.
Time to Disease Recurrence
Length of time participants remain without evidence of disease.
Overall Survival
Length of time until participant death.
Locoregional Control
Number of participants who experience local control of their primary tumors after treatment.
Distant Control
Number of participants who experience control of metastatic disease (distant tumors) after treatment.

Full Information

First Posted
September 17, 2020
Last Updated
July 6, 2023
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT04572100
Brief Title
Pilot Study of Chemotherapy for HPV-Associated Oropharyngeal Cancer
Official Title
Pilot Study of Induction Chemotherapy Followed by Risk and Response-Stratified Treatment for Locoregional HPV Associated Oropharyngeal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
January 9, 2023 (Actual)
Study Completion Date
January 9, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Doctors leading this study will give blood tests to head and neck cancer participants during the beginning of chemotherapy treatment (also known as induction therapy) to see if these blood tests can help predict tumor shrinkage after therapy and reduce the amount of additional radiotherapy or chemotherapy treatment the participant may need. This study will also examine ways to reduce overall side effects of treatment using robotic surgery, chemotherapy and radiotherapy, or radiotherapy alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Squamous Cell Carcinoma
Keywords
Oropharyngeal squamous cell carcinoma, head and neck cancer, HPV, human papillomavirus, OPSCC

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A - Low Risk
Arm Type
Experimental
Arm Description
Participants who have low-risk cancer and significant reduction (greater than 50%) in tumor size following induction therapy will be assigned to this group.
Arm Title
Group B - Intermediate Risk
Arm Type
Experimental
Arm Description
Participants who have low-risk cancer and intermediate reduction (30-50%) in tumor size or high-risk cancer with significant reduction (greater than or equal to 50%) in tumor size following induction therapy will be assigned to this group.
Arm Title
Group C - High-Risk
Arm Type
Experimental
Arm Description
Participants who have high-risk cancer and less than a 50% reduction in their tumor size following induction therapy will be assigned to this group.
Arm Title
Induction Therapy (Carboplatin and Paclitaxel)
Arm Type
Experimental
Arm Description
All study participants will be assigned to this group to first receive induction therapy using a combination of carboplatin and paclitaxel. Participant response to this phase of therapy will determine which group (low-risk, intermediate risk or high-risk) the participant will be in.
Intervention Type
Other
Intervention Name(s)
Transoral Robotic Surgery (TORS) or Radiotherapy
Intervention Description
Participants assigned to this group will receive transoral robotic surgery (TORs) or radiotherapy. Radiotherapy is given once a day for 5 weeks. A percentage of subjects who undergo surgery may need further radiotherapy with or without chemotherapy based on the results of the surgery. TORs is surgery in which a robot with arms is used to remove cancer from hard-to-reach areas of the mouth and throat.
Intervention Type
Other
Intervention Name(s)
Chemotherapy and Low-Dose Radiotherapy
Intervention Description
Participants assigned to this group will receive 5 weeks of chemotherapy combined with low- dose radiotherapy.
Intervention Type
Other
Intervention Name(s)
Chemotherapy and High-Dose Radiotherapy
Intervention Description
Participants assigned to this group will receive 7 weeks of chemotherapy combined with high- dose radiotherapy.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
This drug will be combined with carboplatin during induction therapy for 9 weeks.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
This drug will be combined with paclitaxel during induction therapy for 9 weeks.
Primary Outcome Measure Information:
Title
Feasibility of collection of serial HPV-DNA blood samples in patients undergoing treatment for Oropharyngeal Squamous Cell Carcinoma
Description
To determine if it is possible (feasibility) to measure HPV-DNA using blood tests among participants undergoing induction chemotherapy followed by a second round of response-based therapy for their HPV-associated cancer. This feasibility will be determined by measuring the proportion of patients who complete chemotherapy treatment and HPV-DNA assessments.
Time Frame
16 weeks
Title
Relationship Between HPV-DNA Found in Participant's Blood and Participant Response to Chemotherapy
Description
To evaluate the relationship (aka correlation) between the amount of HPV-DNA found in a participant's plasma/blood and the participant's response to induction chemotherapy based on how their tumor responds to treatment.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Changes in Blood Containing HPV-DNA During Response-Based Therapy
Description
To evaluate changes in blood containing HPV-DNA during a second round of chemotherapy (known as response-based chemo-radiotherapy) that will be based on how the participant responded to their first/induction phase of chemotherapy treatment. This outcome will be measured by checking quantitative HPV DNA in plasma with each cycle of induction chemotherapy, weekly during radiation treatment, and following completion of radiation at set time points within the study.
Time Frame
16 weeks
Title
Side Effects of Cisplatin-Based Chemotherapy Treatment
Description
To evaluate the side effects of weekly cisplatin-based treatment in participants receiving chemotherapy followed by a second round of response-based therapy for their HPV-associated cancer.
Time Frame
16 weeks
Title
Tumor Response Among Participants Undergoing Transoral Robotic Surgery
Description
To determine how participant's tumor/cancer responds when they are undergoing Transoral Robotic Surgery (TORS) following induction chemotherapy. TORs is surgery in which a robot with arms is used to remove cancer from hard-to-reach areas of the mouth and throat. Data about how patients' tumors respond in this study will be compared to similar data from a previous study.
Time Frame
20 weeks
Title
Time to Disease Recurrence
Description
Length of time participants remain without evidence of disease.
Time Frame
5 years
Title
Overall Survival
Description
Length of time until participant death.
Time Frame
5 years
Title
Locoregional Control
Description
Number of participants who experience local control of their primary tumors after treatment.
Time Frame
5 years
Title
Distant Control
Description
Number of participants who experience control of metastatic disease (distant tumors) after treatment.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have clinically confirmed Human papillomavirus(HPV)-positive head and neck squamous cell cancer of the back of the mouth/throat (oropharynx). Confirmed HPV-positive disease of other subsites are uncommon but also eligible. HPV testing must be compliant with the following criteria: P16INK4a immunohistochemistry (p16 IHC) positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al72). p16 IHC positivity is to be validated using an HPV Polymerase chain reaction (PCR - a type of DNA copying method). HPV PCR must demonstrate HPV16 or HPV18 subtype Availability of greater than 10 unstained 5 micron slides (to be provided to HTRC at the University of Chicago). Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study. Participants must be at least 18 years old. Participants with American Joint Committee on Cancer (AJCC) (8th edition, 2018) N1 (>=3cm), N2-N3 nodal disease or T3-T4 primary tumor. Measurable disease (either primary site or nodal disease) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. No previous radiation or chemotherapy for a head and neck cancer. No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or biopsies will occur after baseline scans are performed and measurable lesions are identified. Eastern Cooperate Oncology Group performance status 0-1 Normal organ function clinically confirmed by medical records. Participants must sign a study-specific informed consent form prior to study entry. Participants should have the ability to understand and the willingness to sign a written informed consent document. Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug. Women must not be breastfeeding. Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment. Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s). Exclusion Criteria: Any sign of metastatic disease (M1 disease). Non-HPV16/18 subtype Unidentifiable primary site of cancer. Other medical illnesses that may impair the participant's ability to receive therapy or limit survival. This includes but is not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible (conditions to be reviewed by the PI to confirm eligibility) Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above. Patients receiving other investigational agents. Prior systemic anti-cancer treatment within the last 8 weeks. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment. Has known history of, or any evidence of active, non-infectious pneumonitis. Has a history of HIV. Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible. Has received a live vaccine within 28 days of planned start of study therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ari Rosenberg
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34980038
Citation
Rosenberg AJ, Izumchenko E, Pearson A, Gooi Z, Blair E, Karrison T, Juloori A, Ginat D, Cipriani N, Lingen M, Sloane H, Edelstein DL, Keyser K, Fredebohm J, Holtrup F, Jones FS, Haraf D, Agrawal N, Vokes EE. Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment. BMC Cancer. 2022 Jan 3;22(1):17. doi: 10.1186/s12885-021-09146-z.
Results Reference
derived

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Pilot Study of Chemotherapy for HPV-Associated Oropharyngeal Cancer

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