- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03829722
Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer
March 14, 2024 updated by: University of Michigan Rogel Cancer Center
Phase II Trial of Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-Related Oropharynx Cancer
The purpose of this study is to find out if the addition of nivolumab can improve 2 year progression free survival (PFS) as compared to standard of care of fractionated radiation therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate).
Fractionated means the radiation will be administered in fragments or parts across multiple days.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
PCD details were updated as RECIST is not appropriate for tumor response assessment in this population.
Tumor response will be assessed via clinical assessment and PET response (determining progression and location, if any evidence of disease).
Study Type
Interventional
Enrollment (Actual)
26
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Rogel Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria
- Histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization
- Clinical stage: stage III AJCC 8th edition staging (cT4 or cN3) OR "matted lymph nodes" (defined as 3 LNs abutting one another with loss of intervening fat plane that is replaced with evidence of extracapsular spread)
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- History/physical examination, including documentation of weight within 2 weeks prior to registration;
- FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration; Zubrod Performance Status 0-1 within 2 weeks prior to registration;
- Age ≥ 18;
CBC/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; Platelets ≥ 75,000 cells/mm3; Hemoglobin ≥ 9.0 g/dL AST/ALT <3 x ULN
- Total Bilirubin <1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level < 3 x ULN)
- Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 mL/min within 2 weeks prior to registration;
- Women of childbearing potential must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and for five months after the last treatment. A woman of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause. Men receiving nivolumab who are sexually active with WOCBP must agree to use effective contraception throughout their participation in the treatment phase of the study and for seven months after the last treatment.
- Due to the potential for serious adverse reactions in breastfed infants from carboplatin/paclitaxel and nivolumab, women are advised not to breast-feed during treatment with carboplatin/paclitaxel or nivolumab
- The patient must provide 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 (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
- Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;
- Any history of active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
- Uncontrolled diarrhea;
- Uncontrolled adrenal insufficiency;
- Transmural myocardial infarction within the last 3 months;
- Acute bacterial or fungal infection requiring systemic antibiotics at the time of registration;
- Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
- Acquired Immune Deficiency Syndrome (AIDS) with CD4+ count < 350 cells per microL; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- Women who are breastfeeding and are not willing to discontinue breastfeeding during the trial
- Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite 2 attempts to improve glucose control by fasting duration and adjustment of medications. Patients with diabetes will preferably be scheduled in the morning and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Short bursts of steroids of 5-7 days (for COPD exacerbation or other similar indication) are allowed.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to nivolumab or any of its excipients or known hypersensitivity to carboplatin/paclitaxel.
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Received a live vaccine within 30 days of planned start of study therapy.
- Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
Therapy will continue for 21 weeks total.
This includes 4 doses of of nivolumab (240mg/m2) before and concurrent with RT/carboplatin/paclitaxel and 4 adjuvant nivolumab doses (480mg/m2) after the end of RT.
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Given intravenously (IV), 240 mg every 2 weeks for 4 doses concurrent with radiation therapy (RT).
Following completion of RT, 480 mg given every 4 weeks for 4 doses.
Other Names:
Given IV once per week during radiation therapy (AUC=1).
Other Names:
Given IV once per week during radiation therapy (30mg/m^2)
Other Names:
Given 5 days/week for a total of 35 doses (70 gray total).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: Up to 2 years after completion of study treatment
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Estimated using the Kaplan-Meier method.
Evaluated using imaging and clinical exams
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Up to 2 years after completion of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who progressed in any location
Time Frame: Up to 2 years after completion of study treatment
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To characterize patterns of failure, investigators will summarize the proportion of patients who progressed in any location and whether the first progression was local, regional, distant or in multiple locations.
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Up to 2 years after completion of study treatment
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Overall survival (OS)
Time Frame: Up to 2 years after completion of study treatment
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Estimated using the Kaplan-Meier method
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Up to 2 years after completion of study treatment
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Incidence of acute toxicity
Time Frame: Up to 6 months after completion of study treatment
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Toxicity evaluation per CTCAE v 5.0
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Up to 6 months after completion of study treatment
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Incidence of late toxicity
Time Frame: Up to 2 years after completion of study treatment
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Toxicity evaluation per CTCAE v 5.0
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Up to 2 years after completion of study treatment
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Correlation of mid-treatment FDG-PET scans with post-treatment PET-CT.
Time Frame: 12 weeks after completion of study treatment
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Correlation of metabolic image uptake data on mid-treatment FDG-PET scans performed between fractions 8-12 with standard 12 week post-treatment PET-CT.
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12 weeks after completion of study treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Michelle Mierzwa, M.D., University of Michigan Rogel Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 5, 2019
Primary Completion (Estimated)
September 1, 2024
Study Completion (Estimated)
September 1, 2024
Study Registration Dates
First Submitted
February 1, 2019
First Submitted That Met QC Criteria
February 1, 2019
First Posted (Actual)
February 4, 2019
Study Record Updates
Last Update Posted (Actual)
March 18, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Neoplasms, Squamous Cell
- Carcinoma, Squamous Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Carboplatin
- Paclitaxel
- Nivolumab
Other Study ID Numbers
- UMCC 2018.085
- HUM00154941 (Other Identifier: University of Michigan)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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