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
3 other identifiers
interventional
62
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2014
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2014
CompletedStudy Start
First participant enrolled
September 22, 2014
CompletedFirst Posted
Study publicly available on registry
October 7, 2014
CompletedResults Posted
Study results publicly available
January 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 6, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 6, 2024
CompletedSeptember 24, 2024
September 1, 2024
10 years
September 19, 2014
December 14, 2020
September 9, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
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.
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
Up to 8 weeks after completion of CRT
Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only
Up to 5 years
Overall Survival
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
Up to 5 years
Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement
Up to 5 years
- +1 more secondary outcomes
Other Outcomes (3)
Histologic Appearance of Post-induction Tumor Tissue
Up to 3 months post-treatment
Histologic Appearance of Post-CRT Tumor Tissue
Up to 3 months post-treatment
Changes in Reactive T Cells
Baseline to up to 2 months after radiation therapy
Study Arms (3)
Group A (radiation therapy alone)
EXPERIMENTALPatients undergo radiation therapy once daily for weeks.
Group B (combination chemotherapy, low-dose radiation therapy)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Undergo radiation therapy
Given IV
Given IV
Given PO
Given IV
Correlative studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
University of Chicago
Chicago, Illinois, 60637, United States
Related Publications (1)
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.
PMID: 30481287DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Everett Vokes
- Organization
- University of Chicago
Study Officials
- PRINCIPAL INVESTIGATOR
Everett Vokes, MD
University of Chicago
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2014
First Posted
October 7, 2014
Study Start
September 22, 2014
Primary Completion
September 6, 2024
Study Completion
September 6, 2024
Last Updated
September 24, 2024
Results First Posted
January 8, 2021
Record last verified: 2024-09