Clinical Trials /

Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer

NCT03829722

Description:

The purpose of this study is to find out if the addition of nivolumab can improve 2 year progression free survival (PFS) as compared to standard of care of fractionated radiation therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate). Fractionated means the radiation will be administered in fragments or parts across multiple days.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer
  • Official Title: Phase II Trial of Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-Related Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.085
  • SECONDARY ID: HUM00154941
  • NCT ID: NCT03829722

Conditions

  • Oropharynx Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabOpdivo, BMS-936558, MDX1106, ONO-4538Nivolumab, Carboplatin/Paclitaxel, Radiotherapy
CarboplatinParaplatinNivolumab, Carboplatin/Paclitaxel, Radiotherapy
PaclitaxelTaxolNivolumab, Carboplatin/Paclitaxel, Radiotherapy

Purpose

The purpose of this study is to find out if the addition of nivolumab can improve 2 year progression free survival (PFS) as compared to standard of care of fractionated radiation therapy (RT) and carboplatin/paclitaxel in subjects with high risk HPV-related squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate). Fractionated means the radiation will be administered in fragments or parts across multiple days.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab, Carboplatin/Paclitaxel, RadiotherapyExperimentalTherapy will continue for 21 weeks total. This includes 4 doses of of nivolumab (240mg/m2) before and concurrent with RT/carboplatin/paclitaxel and 4 adjuvant nivolumab doses (480mg/m2) after the end of RT.
  • Nivolumab
  • Carboplatin
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria

          -  Histologically or cytologically proven squamous cell carcinoma of the oropharynx
             (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by
             immunohistochemistry or HPV positive by in situ hybridization

          -  Clinical stage: stage III AJCC 8th edition staging (cT4 or cN3) OR "matted lymph
             nodes" (defined as 3 LNs abutting one another with loss of intervening fat plane that
             is replaced with evidence of extracapsular spread)

          -  Appropriate stage for protocol entry, including no distant metastases, based upon the
             following minimum diagnostic workup:

               -  History/physical examination, including documentation of weight within 2 weeks
                  prior to registration;

               -  FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
                  Zubrod Performance Status 0-1 within 2 weeks prior to registration;

               -  Age ≥ 18;

          -  CBC/differential obtained within 2 weeks prior to registration on study, with adequate
             bone marrow function defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; Platelets ≥ 75,000 cells/mm3;
                  Hemoglobin ≥ 9.0 g/dL AST/ALT <3 x ULN

               -  Total Bilirubin <1.5 x ULN (except subjects with Gilbert Syndrome who must have a
                  total bilirubin level < 3 x ULN)

          -  Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45
             mL/min within 2 weeks prior to registration;

          -  Women of childbearing potential must agree to use a medically effective means of birth
             control throughout their participation in the treatment phase of the study and for
             five months after the last treatment. A woman of childbearing potential (WOCBP) is
             defined as any female who has experienced menarche and who has not undergone surgical
             sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal.
             Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the
             absence of other biological or physiological causes. In addition, females under the
             age of 55 years must have a serum follicle stimulating hormone (FSH) level > 40 mIU/mL
             to confirm menopause. Men receiving nivolumab who are sexually active with WOCBP must
             agree to use effective contraception throughout their participation in the treatment
             phase of the study and for seven months after the last treatment.

          -  Due to the potential for serious adverse reactions in breastfed infants from
             carboplatin/paclitaxel and nivolumab, women are advised not to breast-feed during
             treatment with carboplatin/paclitaxel or nivolumab

          -  The patient must provide study-specific informed consent prior to study entry.

        Exclusion Criteria

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity,
             or cervix are all permissible);

          -  Any prior therapy for the study cancer; note that prior chemotherapy for a different
             cancer is allowable if > 3 years prior to study;

          -  Any history of active autoimmune disease that has required systemic treatment in the
             past 2 years (i.e., with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields;

          -  Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months;

               -  Uncontrolled diarrhea;

               -  Uncontrolled adrenal insufficiency;

               -  Transmural myocardial infarction within the last 3 months;

               -  Acute bacterial or fungal infection requiring systemic antibiotics at the time of
                  registration;

               -  Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy at the time of
                  registration;

               -  Acquired Immune Deficiency Syndrome (AIDS) with CD4+ count < 350 cells per
                  microL; note, however, that HIV testing is not required for entry into this
                  protocol. The need to exclude patients with AIDS from this protocol is necessary
                  because the treatments involved in this protocol may be significantly
                  immunosuppressive.

          -  Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use contraception; this exclusion is necessary because the treatment
             involved in this study may be significantly teratogenic.

          -  Women who are breastfeeding and are not willing to discontinue breastfeeding during
             the trial

          -  Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite 2
             attempts to improve glucose control by fasting duration and adjustment of medications.
             Patients with diabetes will preferably be scheduled in the morning and instructions
             for fasting and use of medications will be provided in consultation with the patients'
             primary physicians

          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. Short bursts of steroids of 5-7 days (for COPD exacerbation or other
             similar indication) are allowed.

          -  Known history of, or any evidence of active, non-infectious pneumonitis.

          -  Known history of active TB (Bacillus Tuberculosis).

          -  Hypersensitivity to nivolumab or any of its excipients or known hypersensitivity to
             carboplatin/paclitaxel.

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Received a live vaccine within 30 days of planned start of study therapy.

          -  Have any condition that, in the opinion of the investigator, would compromise the
             well-being of the subject or the study or prevent the subject from meeting or
             performing study requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 2 years after completion of study treatment
Safety Issue:
Description:Estimated using the Kaplan-Meier method. Evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures

Measure:Proportion of patients who progressed in any location
Time Frame:Up to 2 years after completion of study treatment
Safety Issue:
Description:To characterize patterns of failure, investigators will summarize the proportion of patients who progressed in any location and whether the first progression was local, regional, distant or in multiple locations.
Measure:Overall survival (OS)
Time Frame:Up to 2 years after completion of study treatment
Safety Issue:
Description:Estimated using the Kaplan-Meier method
Measure:Incidence of acute toxicity
Time Frame:Up to 6 months after completion of study treatment
Safety Issue:
Description:Toxicity evaluation per CTCAE v 5.0
Measure:Incidence of late toxicity
Time Frame:Up to 2 years after completion of study treatment
Safety Issue:
Description:Toxicity evaluation per CTCAE v 5.0
Measure:Correlation of mid-treatment FDG-PET scans with post-treatment PET-CT.
Time Frame:12 weeks after completion of study treatment
Safety Issue:
Description:Correlation of metabolic image uptake data on mid-treatment FDG-PET scans performed between fractions 8-12 with standard 12 week post-treatment PET-CT.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

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