Squamous Cell Carcinoma of the OropharynxNCT01663259
Reduced-intensity Therapy for Oropharyngeal Cancer in Non-smoking HPV-16 Positive Patients
A study testing Cetuximab and Radiotherapy in people with Squamous Cell Carcinoma of the Oropharynx and HPV, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
Taking into account the excellent prognosis of patients with HPV-positive oropharyngeal cancer with < 10 pack-year smoking, the investigators hypothesize that reducing the intensity of therapy for these patients will reduce treatment sequelae, notably long-term dysphagia, without affecting their cure rates. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Oropharynx, HPV
- What is being tested?
- Cetuximab and Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Sep 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have pathologically-confirmed, previously untreated,stage III-IV(excluding N3 or T4) squamous cell carcinoma of the oropharynx, without evidence of distant metastasis
- Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required. The tumor must be HPV(+) or p16(+)
- Smoking history <10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana). One cannabis joint is equivalent to 5 cigarettes. (Aldington etal, Thorax 2007; 62:1058-1063). Smoking status definitions (National Health Interview Survey and Behavioral Risk Factor Surveillance System (Nelson DE etal al, Am J Pub Health 2003;93:1335):
- Smokers: smoking now every day or some days in past month
- Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months
- Former smoker: at least 100 cigarettes/lifetime and not smoking >12 months
Show all 18Show fewer
- Never smokers: <100 cigarettes (or equivalent)/lifetime
- KPS > 80 (see Appendix A)
- Patients must undergo pre-treatment endoscopic tumor staging and PET-CT scanning
- Laboratory criteria:
- WBC > 3500/ul
- granulocyte > 1500/ul
- Platelet count > 100,000/ul
- Total Bilirubin < 1.5 X ULN
- AST and ALT < 2.5 X ULN
- Creatinine clearance >30 cc/min
- Patients must sign study specific informed consent
- Patients must have, in the opinion of a treating physician, tumor that is accessible to biopsy in the clinic.
Who cannot join
- Prior head and neck malignancy or history of other prior non-head and neck malignancy (excluding skin cancer and early stage treated prostate cancer) within the past 3 years
- Prior head and neck radiation or chemotherapy
- Any medical or psychiatric illness, which in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment or limit compliance with study requirements
- Patients residing in prison
- Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)
Trial locations and contacts
1 site in 1 country.
United States1 site
Radiation Oncology , University of Michigan Health System
Ann Arbor, Michigan, 48109
About this study
Official title: Reduced-intensity Therapy for Advanced Oropharyngeal Cancer in Non-smoking Human Papilloma Virus (HPV)-16 Positive Patients
Taking into account the excellent prognosis of patients with HPV-positive oropharyngeal cancer with < 10 pack-year smoking, the investigators hypothesize that reducing the intensity of therapy for these patients will reduce treatment sequelae, notably long-term dysphagia, without affecting their cure rates. The main Aim is to assess whether reducing treatment intensity, by replacing concurrent chemotherapy with cetuximab, will indeed achieve improved long-term toxicity.
The primary objectives include the following: to confirm that reducing treatment intensity in patients with HPV-related oropharyngeal cancer and < 10 pack-year smoking history by replacing concurrent chemotherapy with concurrent cetuximab, does not significantly increase the proportion of patients whose tumors recur, compared to our previous experience in similar patients receiving chemo-RT and to compare the toxicity in patients receiving cetuximab-RT to similar patients treated with 7 weeks of chemotherapy concurrent with RT ("standard therapy") in UMCC 2-21.
Read the detailed description
The investigators have shown in past experience a high success in getting rid of oropharyngeal cancer (tonsil or base of tongue cancer) using chemotherapy and radiation therapy in patients who have not smoked, or only smoked a minimal amount of cigarettes or equivalent. In these patients, the cancer is thought to be caused by a virus (Human Papilloma Virus, or HPV). HPV is a virus that infects the epidermis (outermost layer of skin) and mucous membranes of humans. In general, patients with HPV-related cancer such as yours have a better prognosis compared with patients whose tumors are smoking-related. Taking into account the good prognosis, it is possible that reducing the intensity of therapy will not affect the high rate of tumor control, while reducing the side-effects of therapy. In this study, the investigators plan to reduce the intensity of treatment by replacing the currently used chemotherapy drugs with an FDA approved drug, cetuximab, which is a monoclonal antibody to a growth factor which helps cancer cells grow. By opposing the effect of the growth factor, cetuximab may help radiotherapy kill cancer cells without a lot of effect on the normal tissue. It differs from chemotherapy in its more selective activity against tumors compared to normal tissue Cetuximab has the chance to preserve the high rate of success in killing the tumor but may reduce the side effects and complications of therapy in comparison to chemotherapy drugs.
The investigators would also like to know if taking cetuximab has any effect on certain cancer-related molecules in the cancer and the normal cells inside the cheek. They would like to test this by taking a small biopsy of the tumor, as well as a swab of the inside of the cheek, before and shortly after the start of therapy.
- Conditions
- Squamous Cell Carcinoma of the Oropharynx, HPV
- Being tested
- Cetuximab, Radiotherapy
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Before Radiotherapy patients you will receive a single loading dose of cetuximab. Patients will also have two additional biopsies before and after cetuximab to determine how the tumor is affected. A Cetuximab infusion will also be delivered once a week during radiotherapy.Radiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week. In order to evaluate swallowing problems from radiotherapy, patients will undergo an evaluation of swallowing by videofluoroscopy (VF). Quality of Life questionnaires will be given before therapy and periodically up to 36 months after therapy. In order to assess if the tumor was completely eradicated, CT-PET scan will be performed 3 months after the completion of therapy.
RadiotherapyRadiation
Radiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab | Experimental | Not described Receives: Drug: Cetuximab; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Recurrence
Number of patients whose tumors recur (includes local, regional, and distant recurrence; and second primaries).
Note: Research indicates that freedom from local and regional progression (FFLRP) is a more meaningful measure. Therefore, the percentage of patients with FFLRP is included below as a Post-Hoc measure.
Measured: 2 years
Secondary outcomes (5)
Number of Participants With Adverse Events
In order to evaluate the toxicity in patients receiving cetuximab-RT, adverse events were clustered into three categories: None, Mild-Moderate (grade 1 or 2), and Severe (grade 3 or 4). Graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4).
Measured: 3 years
Treatment Related Toxicities
Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the number of incidents outnumbers the number of participants. Toxicities graded according to the CTCAE v4.
Measured: 3 years
Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)
The ratio (fold change) of tumor EGFR post/pre loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Measured: Day 7
Mean Change in Tumor Phosphorylated EGFR (pEGFR)
The ratio (fold change) of tumor pEGFR post/pre loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Measured: Day 7
Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa
Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level post/pre loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post/pre loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startJan 2011
- Primary completionSep 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Carcinoma of the OropharynxStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michelle Mierzwa, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663259
- Sponsor's protocol ID
- UMCC 2009.078
- Other IDs
- HUM00032219
- Status last verified
- Dec 2020
- First submitted
- 23 Jul 2012
- Last updated
- 19 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced-intensity Therapy for Advanced Oropharyngeal Cancer in Non-smoking Human Papilloma Virus (HPV)-16 Positive Patients
- ClinicalTrials.gov ID
- NCT01663259
- Acronym / sponsor ID
- UMCC 2009.078
- Conditions
- Squamous Cell Carcinoma of the Oropharynx, HPV
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Jan 2011 (actual)
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 13 Aug 2012 (estimated)
- Results
- Posted 26 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Taking into account the excellent prognosis of patients with HPV-positive oropharyngeal cancer with < 10 pack-year smoking, the investigators hypothesize that reducing the intensity of therapy for these patients will reduce treatment sequelae, notably long-term dysphagia, without affecting their cure rates. The main Aim is to assess whether reducing treatment intensity, by replacing concurrent chemotherapy with cetuximab, will indeed achieve improved long-term toxicity.
The primary objectives include the following: to confirm that reducing treatment intensity in patients with HPV-related oropharyngeal cancer and < 10 pack-year smoking history by replacing concurrent chemotherapy with concurrent cetuximab, does not significantly increase the proportion of patients whose tumors recur, compared to our previous experience in similar patients receiving chemo-RT and to compare the toxicity in patients receiving cetuximab-RT to similar patients treated with 7 weeks of chemotherapy concurrent with RT ("standard therapy") in UMCC 2-21.
Detailed description
The investigators have shown in past experience a high success in getting rid of oropharyngeal cancer (tonsil or base of tongue cancer) using chemotherapy and radiation therapy in patients who have not smoked, or only smoked a minimal amount of cigarettes or equivalent. In these patients, the cancer is thought to be caused by a virus (Human Papilloma Virus, or HPV). HPV is a virus that infects the epidermis (outermost layer of skin) and mucous membranes of humans. In general, patients with HPV-related cancer such as yours have a better prognosis compared with patients whose tumors are smoking-related. Taking into account the good prognosis, it is possible that reducing the intensity of therapy will not affect the high rate of tumor control, while reducing the side-effects of therapy. In this study, the investigators plan to reduce the intensity of treatment by replacing the currently used chemotherapy drugs with an FDA approved drug, cetuximab, which is a monoclonal antibody to a growth factor which helps cancer cells grow. By opposing the effect of the growth factor, cetuximab may help radiotherapy kill cancer cells without a lot of effect on the normal tissue. It differs from chemotherapy in its more selective activity against tumors compared to normal tissue Cetuximab has the chance to preserve the high rate of success in killing the tumor but may reduce the side effects and complications of therapy in comparison to chemotherapy drugs.
The investigators would also like to know if taking cetuximab has any effect on certain cancer-related molecules in the cancer and the normal cells inside the cheek. They would like to test this by taking a small biopsy of the tumor, as well as a swab of the inside of the cheek, before and shortly after the start of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab | Experimental | Drug: Cetuximab, Radiation: Radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have pathologically-confirmed, previously untreated,stage III-IV(excluding N3 or T4) squamous cell carcinoma of the oropharynx, without evidence of distant metastasis
- Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required. The tumor must be HPV(+) or p16(+)
- Smoking history <10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana). One cannabis joint is equivalent to 5 cigarettes. (Aldington etal, Thorax 2007; 62:1058-1063). Smoking status definitions (National Health Interview Survey and Behavioral Risk Factor Surveillance System (Nelson DE etal al, Am J Pub Health 2003;93:1335):
- Smokers: smoking now every day or some days in past month
- Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months
Key exclusion criteria (5 listed)
- Prior head and neck malignancy or history of other prior non-head and neck malignancy (excluding skin cancer and early stage treated prostate cancer) within the past 3 years
- Prior head and neck radiation or chemotherapy
- Any medical or psychiatric illness, which in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment or limit compliance with study requirements
- Patients residing in prison
- Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabBefore Radiotherapy patients you will receive a single loading dose of cetuximab. Patients will also have two additional biopsies before and after cetuximab to determine how the tumor is affected. A Cetuximab infusion will also be delivered once a week during radiotherapy.Radiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week. In order to evaluate swallowing problems from radiotherapy, patients will undergo an evaluation of swallowing by videofluoroscopy (VF). Quality of Life questionnaires will be given before therapy and periodically up to 36 months after therapy. In order to assess if the tumor was completely eradicated, CT-PET scan will be performed 3 months after the completion of therapy. | Drug | Cetuximab |
| RadiotherapyRadiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week. | Radiation | Cetuximab |
Primary outcome
Rate of Recurrence
Time frame: 2 years
Number of patients whose tumors recur (includes local, regional, and distant recurrence; and second primaries). Note: Research indicates that freedom from local and regional progression (FFLRP) is a more meaningful measure. Therefore, the percentage of patients with FFLRP is included below as a Post-Hoc measure.
5 secondary outcomes
Number of Participants With Adverse Events
Time frame: 3 years
Treatment Related Toxicities
Time frame: 3 years
Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)
Time frame: Day 7
Mean Change in Tumor Phosphorylated EGFR (pEGFR)
Time frame: Day 7
Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa
Time frame: Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Mierzwa, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cetuximab and Radiotherapy in people with Squamous Cell Carcinoma of the Oropharynx and HPV, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Recurrence (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2021.