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Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)

NCT04282109

Description:

Chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma is palliative and usually platinum based, and the patients often present with poor physical condition. Consequently, many of them are not able to withstand a platinum-based chemotherapy. The addition of taxanes to the armamentarium of drugs improve the outcome in this group of patients. An alternative and better tolerated regimen for these patients is paclitaxel in combination with cetuximab, included the in guidelines of the Spanish Society of Medical Oncology. Recently, new treatments such as immune-checkpoint inhibitors have shown promising activity and good tolerability in patients with recurrent or metastatic head and neck squamous cell carcinoma and has been included in the recently published guidelines from the Society for Immunotherapy of Cancer. Nivolumab (anti-PD1) has been approved for patients progressing on or after platinum-based therapy, as it clearly impacts on overall survival. This randomized phase II study will evaluate the efficacy of nivolumab plus paclitaxel for first-line treatment of recurrent or metastatic HNSCC in the platinum ineligible and platinum refractory settings. Control arm will be paclitaxel in combination with cetuximab, treatment included in the guidelines of the Spanish Society of Medical Oncology.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)
  • Official Title: Phase II Multicenter Randomized Trial to Assess the Efficacy and Safety of First Line Nivolumab in Combination With Paclitaxel in Subjects With R/M HNSCC Unable for Cisplatin-based Chemotherapy (NIVOTAX)

Clinical Trial IDs

  • ORG STUDY ID: TTCC-2019-01/CA209-7HE
  • SECONDARY ID: 2019-002922-60
  • NCT ID: NCT04282109

Conditions

  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Head and Neck Cancer Stage IV

Interventions

DrugSynonymsArms
Nivolumab + PaclitaxelArm 1
Cetuximab + PaclitaxelArm 2

Purpose

Chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma is palliative and usually platinum based, and the patients often present with poor physical condition. Consequently, many of them are not able to withstand a platinum-based chemotherapy. The addition of taxanes to the armamentarium of drugs improve the outcome in this group of patients. An alternative and better tolerated regimen for these patients is paclitaxel in combination with cetuximab, included the in guidelines of the Spanish Society of Medical Oncology. Recently, new treatments such as immune-checkpoint inhibitors have shown promising activity and good tolerability in patients with recurrent or metastatic head and neck squamous cell carcinoma and has been included in the recently published guidelines from the Society for Immunotherapy of Cancer. Nivolumab (anti-PD1) has been approved for patients progressing on or after platinum-based therapy, as it clearly impacts on overall survival. This randomized phase II study will evaluate the efficacy of nivolumab plus paclitaxel for first-line treatment of recurrent or metastatic HNSCC in the platinum ineligible and platinum refractory settings. Control arm will be paclitaxel in combination with cetuximab, treatment included in the guidelines of the Spanish Society of Medical Oncology.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalNIVOTAX (nivolumab + paclitaxel)
  • Nivolumab + Paclitaxel
Arm 2Active ComparatorERBITAX (cetuximab + paclitaxel)
  • Cetuximab + Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Voluntary written consent must be given before performance of any study-related
             procedure not part of standard medical care.

          2. Histologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx,
             hypopharynx, larynx) not amenable to therapy with curative intent (surgery or
             radiation therapy with or without chemotherapy).

          3. Patients not previously treated for recurrent/metastatic disease.

          4. Radiographically evaluable disease. Measurable disease as defined by RECIST version
             1.1. Previously irradiated lesions can only be considered as measurable disease if
             disease progression has been unequivocally documented at that site since radiation and
             the previously irradiated lesion is not the only site of disease.

          5. Patients unable for cisplatin-based chemotherapy, defined "unable" by:

               1. Karnofsky 70% or

               2. Karnofsky 80-100% and amenable to chemotherapy, but:

             i. Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could
             be assessed by direct measurement (EDTA or creatinine clearance) if available or by
             calculation from serum or plasma creatinine (see annex 5), or

             ii. grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or

             iii. Class III heart failure according to the New York Heart Association (annex 9), or

             iv. History of allergic reactions to cisplatin, carboplatin, or other
             platinum-containing compounds or

             v. Prior dose of cisplatin ≥225 mg/m² for locally advanced disease (a patient who
             received prior RT + 3 cycles of cisplatin 100 mg/m2 or 3 cycles induction TPF (with
             cisplatin ≥75/m2) for locally advanced primary HN cancer can be included), or

             vi. Disease progression or relapse during or within 6 months of receiving
             platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant
             chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.

          6. Male or female patients aged ≥18 years. Patients aged >70 years old can only be
             included with a G8 (Geriatric 8) health status screening score ≥ 14.

          7. Clinical laboratory values as specified below within 28 days before the first dose of
             study drug:

               1. Total bilirubin must be ≤2 × the upper limit of normal (ULN).

               2. Magnesium ≥ lower limit of normal.

               3. Calcium ≥ lower limit of normal.

               4. ALT and AST must be ≤3 × ULN unless liver metastases are present, in which case
                  they must be ≤5x ULN.

             a. Hemoglobin must be ≥9 g/dL, absolute neutrophil count (ANC) must be ≥1.500/µL, WBC
             must be ≥2.000/µL and platelet count must be ≥100.000/µL.

          8. Subjects who have received radiation as primary therapy are eligible if radiation
             therapy treatment was completed > 4 weeks prior to inclusion.

          9. Subjects who have previously received chemotherapy as part of the initial
             multimodality treatment for locally advanced disease are eligible if the chemotherapy
             was completed > 24 weeks prior to inclusion.

         10. Documentation of PD-L1 status by IHC performed by the central lab at randomization. A
             pre-treatment tumor tissue sample should be sent. If several tumor samples are
             available, testing should be performed on the most recently obtained tumor sample.

         11. Documentation of HPV p16 status (OPC) is required for HNSCC tumor of the oropharynx.
             For subjects with oropharyngeal cancer, sites are defined in annex 8. HPV status of
             tumor tissue has to be locally determined at screening by any of the following
             methods: p16 IHC, in situ hybridization, or polymerase chain reaction based assay. If
             HPV status by p16 IHC is positive result confirmation by PCR is mandatory.

        Exclusion Criteria:

          1. Male or female patients aged <18 years. Patients aged >70 years old should not be
             included with a G8 (Geriatric 8) health status screening score < 14.

          2. Karnofsky <70%.

          3. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy except for
             alopecia, vitiligo, hear loss and the laboratory values defined in the inclusion
             criteria.

          4. Histologically confirmed recurrent or metastatic squamous cell carcinoma of unknown
             primary, of the nasopharynx or non-squamous histologies (eg, mucosal melanoma).

          5. Active brain metastases or leptomeningeal metastases.

          6. Carcinomatous meningitis.

          7. Active, known, or suspected autoimmune disease. Subjects with vitiligo, type I
             diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
             requiring hormone replacement, or unexpected conditions of recurrence in the absence
             of an external trigger are allowed to be included.

          8. Diagnosis of immunodeficiency or any condition requiring systemic treatment with
             either corticosteroids (>10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of treatment.

          9. History of pneumonitis requiring treatment with steroids; history of idiopathic
             pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of
             active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the
             radiation field (fibrosis) is permitted.

         10. Patients with a history of interstitial lung disease cannot be included if they have
             symptomatic ILD (Grade 3-4) and/or poor lung function.

         11. Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents
             or inhibitors of checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells
             are prohibited.

         12. Any serious medical or psychiatric illness, including drug or alcohol abuse, that
             could, in the investigator's opinion, potentially interfere with the completion of
             treatment according to this protocol.

         13. Life-threatening illness unrelated to cancer.

         14. Female patients who are lactating and breast-feeding or a positive serum pregnancy
             test during the screening period.

         15. Systemic anticancer treatment or radiotherapy less than 4 weeks or 5 half-lives,
             whichever is longer, before the first dose of study treatment or not recovered from
             acute toxic effects from prior chemotherapy and radiotherapy.

         16. Prior treatment with investigational agents ≤21 days (≤4 weeks for monoclonal
             antibodies with evidence of PD) or ≤5 their half-lives (whichever is shorter) before
             the first dose of study treatment. A minimum of 10 days should elapse from prior
             therapy to initiating protocol therapy.

         17. Major surgery within 14 days before the first dose of study drug and not recovered
             fully from any complications from surgery.

         18. Systemic infection requiring IV antibiotic therapy or other serious infection within
             14 days before the first dose of study drug.

         19. Known human immunodeficiency virus (HIV) positive (testing not required), or known
             acquired immunodeficiency syndrome (AIDS).

         20. Patients with positive test for hepatitis B virus or hepatitis C virus indicating
             presence of virus, eg, Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C
             antibody (anti-HCV) positive (except if HCV-RNA negative).

         21. Active secondary malignancy that requires treatment. Patients with previous
             malignancies (except non-melanoma skin cancers, and the following in situ cancers:
             bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are
             excluded unless a complete remission was achieved at least 2 years prior to study
             entry and no additional therapy is required during the study period

         22. Any clinically significant co-morbidities, such as uncontrolled pulmonary disease,
             known impaired cardiac function or clinically significant cardiac disease, active
             central nervous system disease, active infection, or any other condition that could
             compromise the patient's participation in the study.

         23. Patients with history of allergy to study drugs components excipients.

         24. Symptomatic peripheral neuropathy of Grade ≥ 2 based on the CTCAE v5.0

         25. Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤
             8 weeks prior to starting the study treatment.

         26. History of severe skin disorder that in the opinion of the investigator may interfere
             with study conduct.

         27. History of hypersensitivity reactions to paclitaxel or other drugs formulated in
             Cremophor® EL (polyoxyethylated castor oil).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Two years overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate (DCR) is defined as the number of subjects with a best overall response (BOR) of a complete response (CR), partial response (PR) or stable disease (SD) divided by the number of randomized subjects for each treatment group.
Measure:Duration of response (DoR)
Time Frame:Up to 5 years
Safety Issue:
Description:Duration of Response (DoR) is defined as the time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first.
Measure:Rate of progressive disease (PD) at 6 months
Time Frame:6 months
Safety Issue:
Description:Rate of PD is defined as the number of subjects with PD at 6 months divided by the number of randomized subjects for each treatment group.
Measure:Five years overall survival (5y-OS)
Time Frame:5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Overall survival in patients ≥ 70 years.
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival in patients ≥ 70 years.
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate in patients ≥ 70 years.
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Overall survival based on PDL1 expression (CPS).
Time Frame:5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival based on PDL1 expression (CPS).
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate based on PDL1 expression (CPS).
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Overall survival based on HPV (OPC).
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival based on HPV (OPC).
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate based on HPV (OPC).
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Overall survival based on cisplatin refractory.
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival based on cisplatin refractory.
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate based on cisplatin refractory.
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Overall survival based on cisplatin ineligibility.
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival based on cisplatin ineligibility.
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate based on cisplatin ineligibility.
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Overall survival based on Karnofsky.
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time between the date of randomization and the date of death.
Measure:Progression free survival based on Karnofsky.
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
Measure:Overall response rate based on Karnofsky.
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.
Measure:Percentage of patients with AEs
Time Frame:2 years
Safety Issue:
Description:Percentage of patients with AEs in relation with total number of treated patients
Measure:Percentage of patients with Grade 3 and Grade 4 AEs
Time Frame:2 years
Safety Issue:
Description:Percentage of patients with Grade 3 and Grade 4 AEs in relation with total number of treated patients
Measure:Percentage of patients with SAEs
Time Frame:5 years
Safety Issue:
Description:Percentage of patients with SAEs in relation with total number of treated patients
Measure:Percentage of patients who discontinued due to AEs
Time Frame:Up to 2 years
Safety Issue:
Description:Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Measure:Percentage of patients with each AE by grade
Time Frame:2 years
Safety Issue:
Description:Percentage of patients with each AE by grade in relation with total number of treated patients

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

Trial Keywords

  • Head and neck cancer
  • Squamous cell carcinoma
  • Nivolumab

Last Updated

June 8, 2020