Human Papilloma VirusPhase 2DEPENDNCT03944915
De-Escalation Therapy for Human Papillomavirus Negative Disease
A Phase 2 study testing Carboplatin, Paclitaxel and Nivolumab in people with Human Papilloma Virus and Squamous Cell Carcinoma, run by University of Chicago at 1 site in United States.
Trial summary
This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Papilloma Virus, Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Carboplatin, Paclitaxel and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2019to 1 Nov 2023
- Phase
- Phase 2
- 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 locally advanced, non-metastatic, HPV-negative head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses.
- Stage IV disease with the exception of nasopharyngeal tumor-3, node-2 (stage III) based of American Joint Committee on Cancer staging 8th edition
- If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out by immunohistochemistry.
- Availability of ≥10 unstained 5 micron slides. Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
- Patients must be at least 18 years of age.
- Measurable disease (either primary site and/or nodal disease) by RECIST criteria.
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- 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 Cooperative Oncology Group performance status 0-1
- Normal Organ Function
- Leukocytes ≥ 3000/mm3
- Platelets ≥ 100,000/mm3
- Absolute neutrophil count ≥ 1,500
- Hemoglobin ≥ 9.0 gm/dL
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5x upper limit of normal
- Alkaline phosphatase ≤ 2.5x upper limit of normal
- Albumin > 2.9 gm/dL
- Total bilirubin ≤ 1.5 mg/dL
- Creatinine clearance > 45 mL/min, normal within 2 weeks prior to start of treatment (Of note, the standard Cockcroft and Gault formula must be used to calculate creatinine clearance (CrCl) for enrollment or dosing)
- Patients must sign a study-specific informed consent form prior to study entry. Patients 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 (minimum sensitivity 25 IU/L or equivalent units of HCG) 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 with study drug(s) plus 6 months after completing chemoradiation or receiving the last dose of consolidative nivolumab, whichever occurs latest.
- 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) plus 6 months after completing chemoradiation or receiving the last dose of consolidative nivolumab, whichever occurs latest.
Who cannot join
- Unequivocal demonstration of distant metastatic disease (M1 disease).
- Unidentifiable primary site.
- Inter-current medical illnesses which would impair patient tolerance to 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.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of physiologic dose or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
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- Known history of active tuberculosis (Bacillus Tuberculosis infection).
- Hypersensitivity to nivolumab or any other drug used in this protocol.
- 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 active autoimmune disease that has required systemic therapy in the past year (i.e. with steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
Official title: A Phase II Trial of Carboplatin, Paclitaxel, and Nivolumab Induction Therapy Followed by Response-stratified Locoregional Therapy for Patients With Locally Advanced, HPV-negative Head and Neck Cancer. The DEPEND Trial.
This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.
- Conditions
- Human Papilloma Virus, Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck, HPV-Related Squamous Cell Carcinoma, HNSCC
- Being tested
- Carboplatin, Paclitaxel, Nivolumab, Radiation, Hydroxyurea Pill
- Medical subject headings
- Carcinoma, Squamous Cell, 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.
CarboplatinDrug
Carboplatin will be given through IV infusions for 30-60 minutes on day 1 of each cycle. Each cycle will last 21 days. There will be 3 cycles.
PaclitaxelDrug
During Induction Therapy Paclitaxel (100 mg) will be given through IV infusions on days 1, 8 and 15 of each 21 day cycle. There will be 3 cycles.
During Radiotherapy, paclitaxel will be given after a dose of radiation by IV infusion for 60 minutes after day 1 of radiotherapy.
NivolumabDrug
Nivolumab will be given through IV infusions at 360 mg on day 1 every 21 days for 3 cycles.
RadiationRadiation
Patients will receive 4.5-5 cycles of radiation depending on response. Those with a positive response will receive radiation for 4.5 cycles with a total radiation dose of 66 Gy. Patients with a moderate or no response will receive 5 cycles with a total radiation dose of 70-75 Gy. 2 times a day for days 1-5 followed by a rest period for days 6-13
Hydroxyurea PillDrug
One dose of hydroxyurea pill by mouth at start of 5-FU infusion during radiotherapy cycle
5-fluorouracilDrug
Also called 5-FU
5-FU will be given by IV infusion continuously for 5 days during radiotherapy cycles
Filgrastim InjectionDrug
Also called Filgrastim shot
Filgrastim shot will be given if patient has certain side effects during radiotherapy cycle on days 6-12.
CisplatinDrug
Radiotherapy may also be given with a different chemotherapy agent called cisplatin. This is the traditional standard of care chemotherapy regimen. In this case, the radiotherapy will be given once daily for 5 days per week. Cisplatin will be administered via IV once every 21 days for 2 or 3 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Standard Chemotherapy | Experimental | Induction Therapy Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Nivolumab |
| De-escalated Chemotherapy | Experimental | Radiation therapy with chemotherapy Receives: Drug: Paclitaxel; Radiation: Radiation; Drug: Hydroxyurea Pill; Drug: 5-fluorouracil; Drug: Filgrastim Injection; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Deep Response Rate (DRR)
DRR is 50% or greater response to induction therapy based on RECIST criteria. The objective is to intensify induction chemotherapy with the addition of an immune checkpoint inhibitor aimed at increasing the proportion of patients achieving a deep tumor response in order to subsequently allow risk-adapted definitive chemoradiotherapy in advanced stage HPV negative head and neck squamous cell cancer patients.
Measured: 2 years
Secondary outcomes (4)
Progression Free Survival Rate (PFS)
Progression free survival at 24 months after completing chemoradiation. PFS will be defined as the time from registration to the date of the first documented disease progression, clinical progression, or death due to any cause, whichever occurs first.
Measured: 26 months
Overall Survival Rate (OS)
Overall survival will be defined as the time between the date of registration and the date of death.
Measured: 26 months
Locoregional Control After Completing Chemoradiation
Assess disease control in all patients receiving induction chemoimmunotherapy and compare disease control between radiation arms.
Measured: 26 months
Distant Control After Completing Chemoradiation
Distant control will be defined as the percent of patients with disease progression below the clavicles. Comparison between the two radiation arms will be made.
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start26 Aug 2019
- Primary completion1 Nov 2023
- Study completion1 Nov 2023
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Papilloma VirusStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Everett Vokes, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944915
- Sponsor's protocol ID
- IRB19-0162
- Acronym
- DEPEND
- Status last verified
- Apr 2025
- First submitted
- 1 May 2019
- Last updated
- 11 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rosenberg AJ, Juloori A, Jelinek MJ, Agrawal N, Cursio JF, Cipriani N, Lingen MW, Izumchenko E, Katipally R, Chin J, Ginat D, Pasternak-Wise O, Gooi Z, Blair E, Pearson AT, Haraf DJ, Vokes EE. Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):492-501. doi: 10.1001/jamaoncol.2025.0081.
PubMed 40048190
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Carboplatin, Paclitaxel, and Nivolumab Induction Therapy Followed by Response-stratified Locoregional Therapy for Patients With Locally Advanced, HPV-negative Head and Neck Cancer. The DEPEND Trial.
- ClinicalTrials.gov ID
- NCT03944915
- Acronym / sponsor ID
- DEPEND / IRB19-0162
- Conditions
- Human Papilloma Virus, Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck, HPV-Related Squamous Cell Carcinoma, HNSCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 26 Aug 2019 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 10 May 2019 (actual)
- Results
- Posted 11 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Chemotherapy | Experimental | Drug: Carboplatin, Drug: Paclitaxel, Drug: NivolumabInduction Therapy |
| De-escalated Chemotherapy | Experimental | Drug: Paclitaxel, Radiation: Radiation, Drug: Hydroxyurea Pill, Drug: 5-fluorouracil, Drug: Filgrastim Injection, Drug: CisplatinRadiation therapy with chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients must have pathologically confirmed locally advanced, non-metastatic, HPV-negative head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses.
- Stage IV disease with the exception of nasopharyngeal tumor-3, node-2 (stage III) based of American Joint Committee on Cancer staging 8th edition
- If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out by immunohistochemistry.
- Availability of ≥10 unstained 5 micron slides. Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
- Patients must be at least 18 years of age.
Key exclusion criteria (15 listed)
- Unequivocal demonstration of distant metastatic disease (M1 disease).
- Unidentifiable primary site.
- Inter-current medical illnesses which would impair patient tolerance to 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.
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 |
|---|---|---|
| CarboplatinCarboplatin will be given through IV infusions for 30-60 minutes on day 1 of each cycle. Each cycle will last 21 days. There will be 3 cycles. | Drug | Standard Chemotherapy |
| PaclitaxelDuring Induction Therapy Paclitaxel (100 mg) will be given through IV infusions on days 1, 8 and 15 of each 21 day cycle. There will be 3 cycles. During Radiotherapy, paclitaxel will be given after a dose of radiation by IV infusion for 60 minutes after day 1 of radiotherapy. | Drug | De-escalated Chemotherapy, Standard Chemotherapy |
| NivolumabNivolumab will be given through IV infusions at 360 mg on day 1 every 21 days for 3 cycles. | Drug | Standard Chemotherapy |
| RadiationPatients will receive 4.5-5 cycles of radiation depending on response. Those with a positive response will receive radiation for 4.5 cycles with a total radiation dose of 66 Gy. Patients with a moderate or no response will receive 5 cycles with a total radiation dose of 70-75 Gy. 2 times a day for days 1-5 followed by a rest period for days 6-13 | Radiation | De-escalated Chemotherapy |
| Hydroxyurea PillOne dose of hydroxyurea pill by mouth at start of 5-FU infusion during radiotherapy cycle | Drug | De-escalated Chemotherapy |
| 5-fluorouracilAlso: 5-FU5-FU will be given by IV infusion continuously for 5 days during radiotherapy cycles | Drug | De-escalated Chemotherapy |
| Filgrastim InjectionAlso: Filgrastim shotFilgrastim shot will be given if patient has certain side effects during radiotherapy cycle on days 6-12. | Drug | De-escalated Chemotherapy |
| CisplatinRadiotherapy may also be given with a different chemotherapy agent called cisplatin. This is the traditional standard of care chemotherapy regimen. In this case, the radiotherapy will be given once daily for 5 days per week. Cisplatin will be administered via IV once every 21 days for 2 or 3 cycles. | Drug | De-escalated Chemotherapy |
Primary outcome
Deep Response Rate (DRR)
Time frame: 2 years
DRR is 50% or greater response to induction therapy based on RECIST criteria. The objective is to intensify induction chemotherapy with the addition of an immune checkpoint inhibitor aimed at increasing the proportion of patients achieving a deep tumor response in order to subsequently allow risk-adapted definitive chemoradiotherapy in advanced stage HPV negative head and neck squamous cell cancer patients.
4 secondary outcomes
Progression Free Survival Rate (PFS)
Time frame: 26 months
Overall Survival Rate (OS)
Time frame: 26 months
Locoregional Control After Completing Chemoradiation
Time frame: 26 months
Distant Control After Completing Chemoradiation
Time frame: 26 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40048190Rosenberg AJ, Juloori A, Jelinek MJ, Agrawal N, Cursio JF, Cipriani N, Lingen MW, Izumchenko E, Katipally R, Chin J, Ginat D, Pasternak-Wise O, Gooi Z, Blair E, Pearson AT, Haraf DJ, Vokes EE. Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):492-501. doi: 10.1001/jamaoncol.2025.0081.
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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.
Everett Vokes, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin, Paclitaxel and Nivolumab in people with Human Papilloma Virus and Squamous Cell Carcinoma, run by University of Chicago 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 24 inclusion and 15 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 11 May 2025. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2025). 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?
Deep Response Rate (DRR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03944915, which also lists 1 linked publication.
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 11 May 2025.