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Nab-Paclitaxel in Combination With Nivolumab to Treat Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma That Progressed on a PD-1 or PD-L1 Inhibitor

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ClinicalTrials.gov Identifier: NCT04831320
Recruitment Status : Not yet recruiting
First Posted : April 5, 2021
Last Update Posted : August 25, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:

The primary hypothesis is that the objective response rate (ORR) with nab-paclitaxel and nivolumab will be significantly higher than the historical control (ORR 30%).

The KEY secondary hypothesis is that the median PFS with nab-paclitaxel and nivolumab will be significantly longer than the historical control (median PFS 3.6 months).


Condition or disease Intervention/treatment Phase
Metastatic Head-and-neck Squamous-cell Carcinoma Drug: nab-paclitaxel Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nab-Paclitaxel in Combination With Nivolumab to Treat Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma That Progressed on a PD-1 or PD-L1 Inhibitor: A Single-Arm, Phase 2 Trial
Estimated Study Start Date : September 30, 2021
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: nab-Paclitaxel + Nivolumab
  • nab-Paclitaxel 125 mg/m^2 intravenous (IV) on days 1, 8 & 15 of each 28-day cycle.
  • Nivolumab 480 mg IV Day 1 of each 28-day cycle.
Drug: nab-paclitaxel
Supplied by Celgene Corporation
Other Name: Abraxane

Drug: Nivolumab
Supplied by Bristol-Myers Squibb
Other Name: Opdivo




Primary Outcome Measures :
  1. Objective response rate (ORR) as assessed by RECIST 1.1 [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
    • ORR: Proportion of patients who achieve a complete or partial response to treatment
    • Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Through completion of follow-up (estimated to be 13 months) ]
    • PFS, defined as the days from the date of treatment to the first documentation of disease progression or death from any cause, whichever occurs first. The alive patients without progression are censored at the date of last follow-up. The patients without progression will not receive anti-cancer therapy, but the patients who have progression may receive additional anti-cancer therapy.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  2. Duration of response (DOR) [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
    • Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  3. Incidence of adverse events [ Time Frame: Through 100 days after completion of treatment (estimated to be 7.5 months) ]
  4. Incidence of immune-related adverse events [ Time Frame: Through 100 days after completion of treatment (estimated to be 7.5 months) ]
  5. Number of dose reductions of nab-paclitaxel [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  6. Number of dose reductions of nivolumab [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  7. Number of dose delays of nab-paclitaxel [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  8. Number of dose delays of nivolumab [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  9. Number of dose interruptions of nab-paclitaxel [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  10. Number of dose interruptions of nivolumab [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
  11. Overall survival (OS) [ Time Frame: Through completion of follow-up (estimated to be 13 months) ]
    -OS: defined as the days from the date of treatment to death from any cause, censored at the date of last follow-up otherwise.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically or cytologically confirmed recurrent or metastatic HNSCC of the oral cavity, larynx, hypopharynx, oropharynx, or p16 positive neck node with unknown primary (but clinically thought to be oropharynx).
  • Known p16 status (positive or negative) if oropharynx or unknown primary of the neck.
  • Measurable disease per RECIST. 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, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • Progression of disease, as assessed by RECIST, that occurred on a PD-1 or PD-L1 inhibitor (given alone or with other therapy) to treat recurrent or metastatic disease. Progression of disease that occurred on a PD-1 or PD-L1 inhibitor given as a component of a curative-intent regimen is excluded.
  • PD-L1 CPS by IHC (22C3 antibody) on tumor tissue must be available or performed, although the test result is not required to enroll onto the trial. Patients with tumor PD-L1 TPS (but not CPS) available are also eligible; but, PD-L1 CPS must be performed in these cases. Fresh tumor tissue (obtained after progression on prior PD-1 or PD-L1 inhibitor given for recurrent or metastatic disease) is strongly preferred, but archived tumor tissue from recurrence is also acceptable.
  • At least 18 years of age.
  • ECOG performance status < 1
  • Normal bone marrow and organ function as defined below:

    • Hemoglobin > 9 g/L
    • Absolute neutrophil count ≥ 1,500/mcl
    • Platelets ≥ 100,000/mcl (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample)
    • Total bilirubin ≤ 1.5 mg/dL
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (in cases of bone mets or liver mets, AST/ALT < 5 x IULN)
    • Serum creatinine <1.5 x IULN or creatinine clearance > 50 mL/min by Cockcroft-Gault
  • The effects of nivolumab and nab-paclitaxel on the developing human fetus are unknown. For this reason and because monoclonal antibodies and antimicrotubule agents are known to be teratogenic, women of childbearing potential (WOCBP) 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 6 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable) before the performance of any protocol-related procedures.

Exclusion Criteria:

  • A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of disease.
  • Has known active CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without any evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and are on stable or tapering doses of steroids for at least 14 days prior to first dose of study treatment.
  • A history of serious allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study (Allergic reaction to cetuximab is allowed as there are other standard of care options for the investigator's choice arm).
  • Receiving systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of treatment. A history of severe autoimmune disorder requiring high-dose corticosteroid treatment due to prior PD-1 inhibitor is an exclusion criterion.
  • Greater than Grade 2 pre-existing peripheral neuropathy (per CTCAE).
  • Uncontrolled serious intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the start of study treatment.
  • Prior organ or allogeneic stem cell transplant.
  • Has an active autoimmune disease (i.e. rheumatoid arthritis, lupus, Sjogren's syndrome) that has required IV or subcutaneous systemic treatment in the past 6 months (excluding Rituxan). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Prisoners, or subjects who are compulsory detained.

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): NCT04831320


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

Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact: Douglas R Adkins, M.D.    314-747-8475    dadkins@wustl.edu   
Principal Investigator: Douglas R Adkins, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Kevin Palka, M.D.         
Sub-Investigator: Esther Lu, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Bristol-Myers Squibb
Investigators
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Principal Investigator: Douglas R Adkins, M.D. Washington University School of Medicine
Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04831320    
Other Study ID Numbers: 202105128
First Posted: April 5, 2021    Key Record Dates
Last Update Posted: August 25, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Paclitaxel
Nivolumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors