Human Papilloma Virus InfectionPhase 2OPTIMANCT02258659
Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer
A Phase 2 study testing paclitaxel albumin-stabilized nanoparticle formulation, carboplatin and radiation therapy in people with Human Papilloma Virus Infection and Stage III Squamous Cell Carcinoma of the Oropharynx, run by University of Chicago at 1 site in United States.
Trial summary
This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and carboplatin followed by response-based local therapy in treating patients with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx
- What is being tested?
- paclitaxel albumin-stabilized nanoparticle formulation, carboplatin and radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2014to 6 Sep 2024
- 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 HPV-positive squamous cell carcinoma
- HPV testing must follow the following criteria
- HPV testing using an E6/E7 based assay is preferred, and does not require any validation (e.g. HPV in situ hybridization [ISH] or HPV E6/E7 polymerase chain reaction [PCR])
- For oropharyngeal tumors p16 immunohistochemistry (IHC) positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan/Lingen et al 2012); it is recommended that p16 IHC positivity is validated at a later point (during or after treatment) using an E6/E7 based test at the University of Chicago and provided slides will be used
- For non-operative (OP) tumors accurate HPV testing (i.e. ISH, or E6/E7 based testing) is required for enrollment and treatment initiation
- Availability of >= 10 unstained 5 micron slides
Show all 23Show fewer
- Patients with American Joint Committee on Cancer (AJCC) (7th edition, 2010) nodal stage N2 or N3 or a T4 primary tumor
- The primary and nodal involvement must be assessable on clinical exam (mucosal and lymph node exam)
- The primary and nodal involvement must have been defined bi- or uni-dimensional measurements measurable by RECIST
- No previous radiation or chemotherapy for a head and neck cancer
- No 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 of the tumor is acceptable)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%)
- Leukocytes >= 3000/mm^3
- Platelets >= 100,000/mm^3
- Absolute neutrophil count >= 1,500
- Hemoglobin > 9.0 gm/dL
- Albumin > 2.9 gm/dL
- Total bilirubin =< 1.5 mg/dl
- Creatinine clearance > 45 mL/min (or serum creatinine [SCr] =< 1.5 mg/dL), normal within 2 weeks prior to start of treatment
- The standard Cockcroft and Gault formula or the measured glomerular filtration rate must be used to calculate creatinine clearance (CrCl) for enrollment or dosing
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal (ULN)
- Alkaline phosphatase =< 2.5 X ULN
- 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
Who cannot join
- Unequivocal demonstration of distant metastases (M1 disease)
- Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival; including but 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
- Pregnant and nursing women are excluded; men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy; women with child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test at screening
- Other coexisting malignancies or malignancies diagnosed within the previous 3 years no evidence of disease for at least 3 years; exceptions to this include non-melanoma skin cancer, cervical cancer in situ, well differentiated thyroid cancer or prostate cancer; other cancers that per assessment of the PI are not prognosis limiting can be allowed after review by the PI
- Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor; residual tumor is required for enrollment on study
- Patients receiving other investigational agents
- Peripheral neuropathy >= grade 1
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Exploratory Pilot Study of Nab-paclitaxel Based Induction Chemotherapy Followed by Response-Stratified Locoregional Therapy for Patients With Stage III and IV HPV-Related Oropharyngeal Cancer - the OPTIMA HPV Trial
This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and carboplatin followed by response-based local therapy in treating patients with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, hydroxyurea, fluorouracil, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving nab-paclitaxel and carboplatin before chemoradiation may make the tumor smaller and reduce the amount of chemotherapy and radiation therapy needed. Assigning chemotherapy and radiation therapy based on response (response-based therapy) and giving patients who are responding well lower doses of treatment may help reduce the occurrence of side effects.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
- Clinical complete response rate (nab-paclitaxel based induction, compared to European Prospective Investigation into Cancer and Nutrition [EPIC] induction [paclitaxel based]).
II. Response rate (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
III. Proportion of patients with >= 50% shrinkage by Response Evaluation Criteria In Solid Tumors (RECIST) (nab-paclitaxel based induction, compared to EPIC induction, paclitaxel based).
IV. Toxicity (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
- To assess swallowing function and speech at 6 months (mos) and 12 mos post therapy.
VI. To determine the rates of late toxicity with chemoradiation following surgery as determined by xerostomia, dental decay, osteroradionecrosis, G-tube dependency, tracheostomy placement and dysphagia.
VII. 2-year overall survival (OS) in patients treated on the Low-Risk, Intermediate-Risk Arm, and High-Risk Arms.
VIII. 2-year PFS in patients treated on the Low-Risk, Intermediate-Risk Arm, and High-Risk Arms - early and late toxicities.
IX. Evaluate need for post radiotherapy/chemoradiotherapy (RT/CRT) surgery on low- and intermediate-risk arms based on response from induction chemotherapy.
- Evaluate in a descriptive manner the role of transoral robotic surgery (TORS) resection/lymph node dissection (LND) when integrated into a de-escalation trial.
TERTIARY OBJECTIVES:
- To evaluate pathologic/histologic appearance of tumor after induction chemotherapy and after CRT.
II. Translational research on blood and tissue samples. III. To profile tumors genetically and immunologically in order to assess in a descriptive manner genetic or immunological features characteristic of clinical behavior.
OUTLINE:
INDUCTION CHEMOTHERAPY: All patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 60 minutes on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are then assigned to 1 of 3 treatment groups based on response to induction chemotherapy.
GROUP A (LOW-DOSE ARM): Patients undergo radiation therapy once daily for 5 weeks.
GROUP B (INTERMEDIATE-DOSE ARM): Patients receive hydroxyurea orally (PO) twice daily (BID) on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
GROUP C (STANDARD-DOSE ARM): Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the principal investigator (PI), patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
After completion of study treatment, patients are followed up for 30 days, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
- Conditions
- Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Oropharynx
- Being tested
- paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, radiation therapy, paclitaxel, fluorouracil
- Medical subject headings
- Papillomavirus Infections, 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.
paclitaxel albumin-stabilized nanoparticle formulationDrug
Also called ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel
Given IV
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
radiation therapyRadiation
Also called irradiation, radiotherapy, therapy, radiation
Undergo radiation therapy
paclitaxelDrug
Also called Anzatax, Asotax, TAX, Taxol
Given IV
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given IV
hydroxyureaDrug
Also called HU, HYD, Hydrea, Hydroxycarbamide
Given PO
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
laboratory biomarker analysisOther
Correlative studies
quality-of-life assessmentProcedure or surgery
Also called quality of life assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Group A (radiation therapy alone) | Experimental | Patients undergo radiation therapy once daily for weeks. Receives: Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: carboplatin; Radiation: radiation therapy; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment |
| Group B (combination chemotherapy, low-dose radiation therapy) | Experimental | Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: carboplatin; Radiation: radiation therapy; Drug: paclitaxel; Drug: fluorouracil; Drug: hydroxyurea; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment |
| Group C (combination chemotherapy, high-dose radiation) | Experimental | Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy. Receives: Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: carboplatin; Radiation: radiation therapy; Drug: paclitaxel; Drug: fluorouracil; Drug: hydroxyurea; Drug: cisplatin; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1
If all patients are followed for two years, the PFS rate and confidence interval will be determined based on the exact binomial distribution. Otherwise, PFS will be estimated using the Kaplan-Meier method and a (large-sample) one-sided 90% confidence interval will be derived for the PFS rate at two years to test the non-inferiority hypothesis. Median PFS will be estimated as described in Brookmeyer and Crowley.
Measured: Time from enrollment until disease progression or death from any cause, assessed at 2 years
Secondary outcomes (6)
Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1
Pathologic response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.
Measured: Up to 8 weeks after completion of CRT
Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only
Clinical response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.
Measured: Up to 5 years
Overall Survival
Overall survival rate
Measured: From the date of registration to the date of death or date of last patient contact if censored, assessed up to 5 years
Cancer-specific Survival
Overall Cancer-specific survival rate. Patients dying from non-cancer related causes will be censored at the time of death.
Measured: Up to 5 years
Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement
Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of acute (mucositis, xerostomia, anorexia, weight loss, dermatitis and G-tube placement) toxicities will be estimated along with 95% confidence intervals. Toxicity criteria of the Common Toxicity Criteria (CTC) and the Radiation Therapy Oncology Group (RTOG) will be used to determine grades. General CTC grade definitions: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. For Mucous, 3 = Confluent fibrinous, mucositis / may include severe pain requiring narcotic; 4 = Ulceration, hemorrhage or necrosis. For neutropenia, 3 = Neutrophils 0.5 - < 1.0; 4 = Neutrophils < 0.5 or sepsis.
Measured: Up to 5 years
Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia
Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of late-term (xerostomia, dental decay, osteroradionecrosis, G-tube dependency, speech abnormalities, tracheostomy placement and dysphagia) toxicities will be estimated along with 95% confidence intervals.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study start22 Sep 2014
- Primary completion6 Sep 2024
- Study completion6 Sep 2024
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 Virus InfectionStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Everett Vokes, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258659
- Sponsor's protocol ID
- IRB14-0639
- Other IDs
- NCI-2014-01867, IRB14-0639, P30CA014599
- Acronym
- OPTIMA
- Status last verified
- Sep 2024
- First submitted
- 19 Sep 2014
- Last updated
- 24 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, Portugal L, Brisson RJ, Dekker A, Kochanny S, Gooi Z, Lingen MW, Villaflor VM, Ginat DT, Haraf DJ, Vokes EE. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019 Feb 1;30(2):297-302. doi: 10.1093/annonc/mdy522.
PubMed 30481287
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Pilot Study of Nab-paclitaxel Based Induction Chemotherapy Followed by Response-Stratified Locoregional Therapy for Patients With Stage III and IV HPV-Related Oropharyngeal Cancer - the OPTIMA HPV Trial
- ClinicalTrials.gov ID
- NCT02258659
- Acronym / sponsor ID
- OPTIMA / IRB14-0639
- Conditions
- Human Papilloma Virus Infection, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Oropharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 22 Sep 2014 (actual)
- Primary completion
- 6 Sep 2024 (actual)
- Study completion
- 6 Sep 2024 (actual)
- First posted
- 7 Oct 2014 (estimated)
- Results
- Posted 8 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and carboplatin followed by response-based local therapy in treating patients with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, hydroxyurea, fluorouracil, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving nab-paclitaxel and carboplatin before chemoradiation may make the tumor smaller and reduce the amount of chemotherapy and radiation therapy needed. Assigning chemotherapy and radiation therapy based on response (response-based therapy) and giving patients who are responding well lower doses of treatment may help reduce the occurrence of side effects.
Detailed description
PRIMARY OBJECTIVES:
- To determine the 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
- Clinical complete response rate (nab-paclitaxel based induction, compared to European Prospective Investigation into Cancer and Nutrition [EPIC] induction [paclitaxel based]).
II. Response rate (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
III. Proportion of patients with >= 50% shrinkage by Response Evaluation Criteria In Solid Tumors (RECIST) (nab-paclitaxel based induction, compared to EPIC induction, paclitaxel based).
IV. Toxicity (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
- To assess swallowing function and speech at 6 months (mos) and 12 mos post therapy.
VI. To determine the rates of late toxicity with chemoradiation following surgery as determined by xerostomia, dental decay, osteroradionecrosis, G-tube dependency, tracheostomy placement and dysphagia.
VII. 2-year overall survival (OS) in patients treated on the Low-Risk, Intermediate-Risk Arm, and High-Risk Arms.
VIII. 2-year PFS in patients treated on the Low-Risk, Intermediate-Risk Arm, and High-Risk Arms - early and late toxicities.
IX. Evaluate need for post radiotherapy/chemoradiotherapy (RT/CRT) surgery on low- and intermediate-risk arms based on response from induction chemotherapy.
- Evaluate in a descriptive manner the role of transoral robotic surgery (TORS) resection/lymph node dissection (LND) when integrated into a de-escalation trial.
TERTIARY OBJECTIVES:
- To evaluate pathologic/histologic appearance of tumor after induction chemotherapy and after CRT.
II. Translational research on blood and tissue samples. III. To profile tumors genetically and immunologically in order to assess in a descriptive manner genetic or immunological features characteristic of clinical behavior.
OUTLINE:
INDUCTION CHEMOTHERAPY: All patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 60 minutes on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are then assigned to 1 of 3 treatment groups based on response to induction chemotherapy.
GROUP A (LOW-DOSE ARM): Patients undergo radiation therapy once daily for 5 weeks.
GROUP B (INTERMEDIATE-DOSE ARM): Patients receive hydroxyurea orally (PO) twice daily (BID) on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
GROUP C (STANDARD-DOSE ARM): Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the principal investigator (PI), patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
After completion of study treatment, patients are followed up for 30 days, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A (radiation therapy alone) | Experimental | Drug: paclitaxel albumin-stabilized nanoparticle formulation, Drug: carboplatin, Radiation: radiation therapy, Other: laboratory biomarker analysis, Procedure: quality-of-life assessmentPatients undergo radiation therapy once daily for weeks. |
| Group B (combination chemotherapy, low-dose radiation therapy) | Experimental | Drug: paclitaxel albumin-stabilized nanoparticle formulation, Drug: carboplatin, Radiation: radiation therapy, Drug: paclitaxel, Drug: fluorouracil, Drug: hydroxyurea, Other: laboratory biomarker analysis, Procedure: quality-of-life assessmentPatients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. |
| Group C (combination chemotherapy, high-dose radiation) | Experimental | Drug: paclitaxel albumin-stabilized nanoparticle formulation, Drug: carboplatin, Radiation: radiation therapy, Drug: paclitaxel, Drug: fluorouracil, Drug: hydroxyurea, Drug: cisplatin, Other: laboratory biomarker analysis, Procedure: quality-of-life assessmentPatients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.* *NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients must have pathologically confirmed HPV-positive squamous cell carcinoma
- HPV testing must follow the following criteria
- Availability of >= 10 unstained 5 micron slides
- Patients with American Joint Committee on Cancer (AJCC) (7th edition, 2010) nodal stage N2 or N3 or a T4 primary tumor
- The primary and nodal involvement must be assessable on clinical exam (mucosal and lymph node exam)
Key exclusion criteria (7 listed)
- Unequivocal demonstration of distant metastases (M1 disease)
- Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival; including but 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
- Pregnant and nursing women are excluded; men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy; women with child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test at screening
- Other coexisting malignancies or malignancies diagnosed within the previous 3 years no evidence of disease for at least 3 years; exceptions to this include non-melanoma skin cancer, cervical cancer in situ, well differentiated thyroid cancer or prostate cancer; other cancers that per assessment of the PI are not prognosis limiting can be allowed after review by the PI
- Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor; residual tumor is required for enrollment on study
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 |
|---|---|---|
| paclitaxel albumin-stabilized nanoparticle formulationAlso: ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxelGiven IV | Drug | Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| carboplatinAlso: Carboplat, CBDCA, JM-8, ParaplatGiven IV | Drug | Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| radiation therapyAlso: irradiation, radiotherapy, therapy, radiationUndergo radiation therapy | Radiation | Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| paclitaxelAlso: Anzatax, Asotax, TAX, TaxolGiven IV | Drug | Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven IV | Drug | Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| hydroxyureaAlso: HU, HYD, Hydrea, HydroxycarbamideGiven PO | Drug | Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Group C (combination chemotherapy, high-dose radiation) |
| laboratory biomarker analysisCorrelative studies | Other | Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Procedure or surgery | Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation) |
Primary outcome
Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1
Time frame: Time from enrollment until disease progression or death from any cause, assessed at 2 years
If all patients are followed for two years, the PFS rate and confidence interval will be determined based on the exact binomial distribution. Otherwise, PFS will be estimated using the Kaplan-Meier method and a (large-sample) one-sided 90% confidence interval will be derived for the PFS rate at two years to test the non-inferiority hypothesis. Median PFS will be estimated as described in Brookmeyer and Crowley.
6 secondary outcomes
Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1
Time frame: Up to 8 weeks after completion of CRT
Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only
Time frame: Up to 5 years
Overall Survival
Time frame: From the date of registration to the date of death or date of last patient contact if censored, assessed up to 5 years
Cancer-specific Survival
Time frame: Up to 5 years
Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement
Time frame: Up to 5 years
Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30481287Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, Portugal L, Brisson RJ, Dekker A, Kochanny S, Gooi Z, Lingen MW, Villaflor VM, Ginat DT, Haraf DJ, Vokes EE. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019 Feb 1;30(2):297-302. doi: 10.1093/annonc/mdy522.
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Not yet recruitingPhase 1/2
Clinical Trial to Assess the Safety, Tolerability, Reactogenicity, and Immunogenicity of a 10 Valent Human Papillomavirus Virus (10vHPV) Vaccine
Human Papillomavirus Infection
Active, not recruitingPhase 4
Comparing Immune Response of 2 vs 3 HPV Doses (27-45 Years Old)
Immunization, HPV Infection
Not yet recruitingPhase 2
Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)
Respiratory Recurrent Papillomatosis (RRP), Human Papillomavirus (HPV)
RecruitingPhase 2
A Study of the Preliminary Efficacy of DARE-HPV to Treat High-risk Persistent Human Papillomavirus (hrHPV)
Human Papilloma Virus (HPV), High-risk Human Papillomavirus Infection
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
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 paclitaxel albumin-stabilized nanoparticle formulation, carboplatin and radiation therapy in people with Human Papilloma Virus Infection and Stage III Squamous Cell Carcinoma of the Oropharynx, 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 23 inclusion and 7 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 24 Sep 2024. 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 8 Jan 2021). 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?
Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1 (time frame: Time from enrollment until disease progression or death from any cause, assessed at 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 NCT02258659, 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 24 Sep 2024.