Clinical Trials /

Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer

NCT02258659

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Nab-paclitaxel</span> and <span class="go-doc-concept go-doc-intervention">Carboplatin</span> Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer

Title

  • Brief Title: Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02258659

    ORG ID: IRB14-0639

    NCI ID: NCI-2014-01867

    Trial 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

    Trial Interventions

    Drug Synonyms Arms
    paclitaxel albumin-stabilized nanoparticle formulation ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation)
    carboplatin Carboplat, CBDCA, JM-8, Paraplat, Paraplatin Group A (radiation therapy alone), Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation)
    paclitaxel Anzatax, Asotax, TAX, Taxol Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation)
    fluorouracil 5-fluorouracil, 5-Fluracil, 5-FU Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation)
    hydroxyurea HU, HYD, Hydrea, Hydroxycarbamide, Hydurea Group B (combination chemotherapy, low-dose radiation therapy), Group C (combination chemotherapy, high-dose radiation)
    cisplatin CACP, CDDP, CPDD, DDP Group C (combination chemotherapy, high-dose radiation)

    Trial Purpose

    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:

    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.

    Trial Arms

    Name Type Description Interventions
    Group A (radiation therapy alone) Experimental Patients undergo radiation therapy once daily for weeks. paclitaxel albumin-stabilized nanoparticle formulation, carboplatin
    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. paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, paclitaxel, fluorouracil, hydroxyurea
    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. paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, paclitaxel, fluorouracil, hydroxyurea, cisplatin

    Eligibility Criteria

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS, evaluated using RECIST version (v) 1.1

    Secondary Outcome Measures

    Rate of pathologic complete response on post treatment biopsy/surgery, evaluated using RECIST v1.1

    Clinical complete response by positron emission tomography, evaluated using RECIST v1.1

    Overall survival

    Cancer-specific survival

    Rates of acute toxicity, determined by incidence of mucositis, xerostomia, anorexia, weight loss, dermatitis and G-tube placement

    Rates of late toxicity, determined by incidence of xerostomia, dental decay, osteroradionecrosis, G-tube dependency, tracheostomy placement and dysphagia

    Trial Keywords