- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02258659
Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer (OPTIMA)
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
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. 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]).
V. 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.
X. 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:
I. 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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
|
Correlative studies
Ancillary studies
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo radiation therapy
Other Names:
|
Experimental: Group B (combination chemotherapy, low-dose radiation therapy)
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.
|
Correlative studies
Given IV
Other Names:
Ancillary studies
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo radiation therapy
Other Names:
Given PO
Other Names:
|
Experimental: Group C (combination chemotherapy, high-dose radiation)
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. |
Correlative studies
Given IV
Other Names:
Ancillary studies
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo radiation therapy
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Time from enrollment until disease progression or death from any cause, assessed at 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Pathologic response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.
|
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
|
Clinical response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.
|
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
|
Overall survival rate
|
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
|
Overall Cancer-specific survival rate.
Patients dying from non-cancer related causes will be censored at the time of death.
|
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
|
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.
|
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
|
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.
|
Up to 5 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Histologic Appearance of Post-induction Tumor Tissue
Time Frame: Up to 3 months post-treatment
|
Results of pathology/histologic review of post induction biopsy specimens will be descriptive and summarize in tabular format.
|
Up to 3 months post-treatment
|
Histologic Appearance of Post-CRT Tumor Tissue
Time Frame: Up to 3 months post-treatment
|
Results of pathology/histologic review of post induction biopsy specimens will be descriptive and summarize in tabular format.
|
Up to 3 months post-treatment
|
Changes in Reactive T Cells
Time Frame: Baseline to up to 2 months after radiation therapy
|
Changes in reactive T cells over time will be assessed using mixed effects models and simple paired t-tests.
|
Baseline to up to 2 months after radiation therapy
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Everett Vokes, MD, University of Chicago
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Virus Diseases
- Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Head and Neck Neoplasms
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Squamous Cell
- Urogenital Diseases
- Genital Diseases
- Carcinoma
- Carcinoma, Squamous Cell
- Oropharyngeal Neoplasms
- Papillomavirus Infections
- Papilloma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antisickling Agents
- Carboplatin
- Paclitaxel
- Fluorouracil
- Albumin-Bound Paclitaxel
- Hydroxyurea
Other Study ID Numbers
- IRB14-0639 (Other Identifier: University of Chicago)
- P30CA014599 (U.S. NIH Grant/Contract)
- NCI-2014-01867 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
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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