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Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC) (APA)

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ClinicalTrials.gov Identifier: NCT02573493
Recruitment Status : Recruiting
First Posted : October 9, 2015
Last Update Posted : July 5, 2017
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
In this trial, the objectives are to determine the efficacy and toxicity of induction chemotherapy (IC) with nab-paclitaxel + cisplatin (Arm 1: AP) and with nab-paclitaxel (Arm 2: A) alone in patients with HNSCC, and to compare these data to nab-paclitaxel, cisplatin, and 5-FU (APF). The investigators also hypothesize that the high anti-tumor efficacy of nab-paclitaxel in HNSCC is due to the upregulation of macropinocytosis, a result of the frequent presence of Ras and PI3K (and epidermal growth factor receptor -EGFR) activation in this cancer.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck Carcinoma, Squamous Cell of the Head and Neck Cancer of Head and Neck Cancer of the Head and Neck Head and Neck Cancer Neoplasms, Head and Neck Drug: nab-Paclitaxel Drug: Cisplatin Biological: Cetuximab Radiation: Intensity-Modulated Radiation Therapy Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Non-Randomized Two Arm Trial of Induction Chemotherapy With Nab-Paclitaxel and Cisplatin (AP: Arm 1) or Single Agent Nab-paclitaxel (A: Arm 2) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC): "The APA Trial".
Actual Study Start Date : April 13, 2016
Estimated Primary Completion Date : May 31, 2018
Estimated Study Completion Date : October 31, 2028

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm 1: nab-Paclitaxel and cisplatin (AP)
  • Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
  • If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
  • If <PR, move directly to CRT if not surgical candidates.
  • CRT includes cisplatin which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
  • It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Cisplatin
Other Names:
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • DDP
Radiation: Intensity-Modulated Radiation Therapy
Other Name: IMRT
Experimental: Arm 2: nab-Paclitaxel (A)
  • Six weeks of nab-paclitaxel (100 mg/m2/week) followed by primary tumor site (PTS) assessment
  • If CR/PR, three more weeks of nab-paclitaxel followed by CRT
  • If <PR, move directly to CRT if not surgical candidates.
  • CRT includes cetuximab will will begin 1 to 35 days after completion of cycle -Cetuximab will be started 7 days before starting definitive radiation therapy. The initial loading dose of cetuximab will be 400 mg/m^2. Subsequently, cetuximab will be given weekly at a dose of 250 mg/m^2 for seven additional doses concurrently with radiation therapy.
  • It is strongly recommended that IMRT begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.
Drug: nab-Paclitaxel
Other Name: Abraxane
Biological: Cetuximab
Other Name: Erbitux®
Radiation: Intensity-Modulated Radiation Therapy
Other Name: IMRT



Primary Outcome Measures :
  1. Complete response rate as measured by clinical exam at the primary tumor site [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    • Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ear, nose, and throat (ENT) physician's clinical exam note.
    • Complete response = complete resolution - 100% decrease/minimal residual mucosal abnormality


Secondary Outcome Measures :
  1. Partial response rate as measured by clinical exam at the primary tumor site [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    • Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ENT physician's clinical exam note.
    • Partial response - 99-50% decrease

  2. Complete response rate as measured by clinical exam at the involved regional nodes [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    • The involved neck node response to the first two cycles of induction will be assessed using visual categorical response. The neck node measurements will be performed clinically by the treating medical oncology physician and dictated in his/her assessment note.
    • Complete response - complete resolution - 100% decrease/minimal residual mucosal abnormality

  3. Partial response rate as measured by clinical exam at the involved regional nodes [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    • The involved neck node response to the first two cycles of induction will be assessed using visual categorical response. The neck node measurements will be performed clinically by the treating medical oncology physician and dictated in his/her assessment note.
    • Partial response - 99%-50% decrease

  4. Anatomic tumor response as assessed by CT using RECIST 1.0 criteria [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    -Computed tomography (CT) scan (intravenous contrast preferred) to document and measure the extent of the primary tumor size and involved regional neck nodes. RECIST 1.0 will be used to determine response at the primary tumor site, at the involved regional neck nodes and the radiographic overall tumor response.

  5. Metabolic tumor response by Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET/CT) fusion scan [ Time Frame: Completion of 2 cycles (approximately 6 weeks) ]
    • Complete Metabolic Response: Complete resolution of all lesions & no new lesions.
    • Partial Metabolic Response: 20% or greater decrease in maximum standardized uptake value (SUV) from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions. Decrease in total number of non-target lesions, without complete resolution of metabolically active disease, or unequivocal decrease in degree of FDG activity within > 50% of the lesions. No unequivocal new lesions.
    • Stable Metabolic Disease: Does not qualify for any other categories.
    • Progressive Metabolic Disease: Unequivocal development of one or more new metabolically active lesion(s). Target lesions: 20% or greater increase in maximum SUV from baseline. Non-target lesions: unequivocal increase in FDG activity within non-target lesions on PET. Unequivocal increase in size of target or non-target lesions on PET.

  6. Document and quantify Ki-67 expression by IHC in primary tumor tissue and correlate with clinical primary tumor site response [ Time Frame: Completion of 2 cycles (approximately 42 days) ]
  7. Grade 3-4 adverse events as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: 30 days after completion of treatment (estimated to be 22-27 weeks) ]
    compare to those observed with APF with the objective that Arm 1 will be at least 25% lower than the risk of Grade 3-4 AE's during APF (40% decreased to 30%) and Arm 2 will be at least 50% lower than the risk of Grade 3-4 AE's during APF (40% decreased to 20%).

  8. Overall survival (OS) [ Time Frame: 10 years ]
    OS: duration of time from start of treatment to time of death from any cause

  9. Disease-free survival (DFS) [ Time Frame: 10 years ]
  10. Progression-free survival (PFS) [ Time Frame: 10 years ]
    ◦PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.

  11. Quality of life as measured by FACT-H&N and FACT/GOG-NTX-4 [ Time Frame: Through one year after completion of treatment (approximately 74 weeks) ]
    • The FACT/GOG-NTX-4 questionnaire has 4 questions with answers ranging from 0 (Not at all) to 4 (Very Much)
    • The FACT-H&N has 5 sections including physical well-being, social/family well being, emotional well-being, functional well-being, and additional concerns.
    • The answers range from 0 (Not at all) to 4 (Very Much)

  12. Overall survival (OS) rate [ Time Frame: 1 year ]
    OS: duration of time from start of treatment to time of death from any cause

  13. Overall survival (OS) rate [ Time Frame: 2 years ]
    OS: duration of time from start of treatment to time of death from any cause

  14. Disease-free survival (DFS) rate [ Time Frame: 1 year ]
  15. Disease-free survival (DFS) rate [ Time Frame: 2 years ]
  16. Progression-free survival (PFS) rate [ Time Frame: 1 year ]
    ◦PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.

  17. Progression-free survival (PFS) rate [ Time Frame: 2 years ]
    ◦PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Arm 1 - AP

  • Diagnosis of selected Stage III or IVa/b HNSCC. All patients must have T2-T4 primary tumors. (Patients with T1 tumors will be excluded). Although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible.
  • Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites.
  • Presence of measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan.
  • At least 18 years of age.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Able to understand and willing to sign an IRB-approved written informed consent document.
  • ECOG performance status ≤ 1.
  • Adequate bone marrow and organ function as defined below:

    • ANC: ≥ 1500/mcL.
    • Platelets: > 100,000/mcL.
    • Hemoglobin > 9.0 g/dL
    • Total bilirubin ≤ 1.5 mg/dL
    • AST/ALT/alkaline phosphatase: ≤ 2.5 x ULN.
    • Serum creatinine: < 1.5 mg/dL or calculated GFR ≥ 75 cc/min. CrCl by Cockcroft Gault will be used to estimate GFR.
    • Pulmonary: no requirement for supplemental oxygen and no evidence of moderate-severe chronic obstructive pulmonary disease (COPD) by pulmonary function tests (PFTs).

Inclusion Criteria: Arm 2 - A

  • Diagnosis of selected Stage III or IVa/b HNSCC. All patients must have T2-T4 primary tumors. (Patients with T1 tumors will be excluded). Although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible.
  • Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites.
  • Presence of measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan.
  • At least 18 years of age.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Able to understand and willing to sign an IRB-approved written informed consent document.
  • ECOG performance status < 3.
  • Adequate bone marrow and organ function as defined below:

    • ANC: ≥ 1500/mcL.
    • Platelets: ≥ 100,000/mcL.
    • Hemoglobin > 9.0 g/dL
    • Total bilirubin ≤ 2.0 mg/dL
    • AST/ALT/alkaline phosphatase: ≤ 5x ULN.
    • Calculated GFR >30 cc/min. CrCl by Cockcroft Gault will be used to estimate GFR.
    • Pulmonary: patients with a requirement for supplemental oxygen or evidence of moderate-severe COPD by PFTs are permitted to enroll.
  • If a patient fully meets criteria for Arm 1, but has profound hearing loss and the physician feels that the patient should not receive Cisplatin, the patient will be eligible for Arm 2.
  • If a patient fully meets criteria for Arm 1, but has a history of solid organ or bone marrow transplant, the patient will be eligible for Arm 2 (due to contraindications of Cisplatin with medications the patient is taking due to the transplant).

Exclusion Criteria (Arm 1 and Arm 2)

  • Prior chemotherapy, prior EGFR targeted therapy, or prior radiation therapy for HNSCC.
  • Disease at the nasopharyngeal, sinus, oral cavity, or other sub-site not specified as eligible.
  • Diagnosis of unknown primary squamous cell carcinoma of the head and neck.
  • History of prior invasive malignancy diagnosed within 3 years prior to study enrollment; exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) that were treated with an expected curative outcome, such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
  • Receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in this study.
  • Taking cimetidine or allopurinol. If currently taking either of these medications, patient must discontinue for one week before receiving treatment with nab-paclitaxel.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. A negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential.
  • Known to be HIV-positive on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study agents. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Peripheral neuropathy > grade 1.
  • Patients with uncontrolled diabetes or fasting blood glucose > 200 mg/dL may enroll but will not be evaluable for PET imaging.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573493


Contacts
Contact: Douglas Adkins, M.D. 314-747-8475 dadkins@wustl.edu

Locations
United States, Kansas
The University of Kansas Cancer Center and Medical Pavilion Recruiting
Westwood, Kansas, United States, 66205
Contact: Prakash Neupane, M.D.    913-588-1227    pneupane@kumc.edu   
Principal Investigator: Prakash Neupane, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Douglas Adkins, M.D.    314-747-8475    dadkins@wustl.edu   
Principal Investigator: Douglas Adkins, M.D.         
Sub-Investigator: Mackenzie Daly, M.D.         
Sub-Investigator: Farrokh Dehdashti, M.D.         
Sub-Investigator: Hiram Gay, M.D.         
Sub-Investigator: Ryan Jackson, M.D.         
Sub-Investigator: Brian Nussenbaum, M.D.         
Sub-Investigator: Randall Paniello, M.D.         
Sub-Investigator: Jason Rich, M.D.         
Sub-Investigator: Barry A Siegel, M.D.         
Sub-Investigator: Wade Thorstad, M.D.         
Sub-Investigator: Tanya Wildes, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Celgene Corporation
Investigators
Principal Investigator: Douglas Adkins, M.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02573493     History of Changes
Other Study ID Numbers: 201510013
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: July 5, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action