Clinical Trials /

Nivolumab + Chemoradiation in Stage II-IVB Nasopharyngeal Carcinoma (NPC)

NCT03267498

Description:

This phase II trial studies how well nivolumab and chemoradiotherapy works in treating patients with stage II-IVB nasopharyngeal cancer. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells. Chemoradiotherapy is the combination of chemotherapy and radiation therapy and may prevent the cancer from spreading when combined with nivolumab. Giving nivolumab and chemoradiotherapy may work better in treating patients with stage II-IVB nasopharyngeal cancer.

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab + Chemoradiation in Stage II-IVB Nasopharyngeal Carcinoma (NPC)
  • Official Title: Nivolumab in Combination With Chemoradiation for Patients With Stage II-IVB Nasopharyngeal Carcinoma, A Phase II Study With Correlative Biomarkers

Clinical Trial IDs

  • ORG STUDY ID: 162010
  • SECONDARY ID: NCI-2017-02291
  • NCT ID: NCT03267498

Conditions

  • Nasopharyngeal Carcinoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab + chemoradiation
CisplatinNivolumab + chemoradiation

Purpose

This phase II trial studies how well nivolumab and chemoradiotherapy works in treating patients with stage II-IVB nasopharyngeal cancer. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells. Chemoradiotherapy is the combination of chemotherapy and radiation therapy and may prevent the cancer from spreading when combined with nivolumab. Giving nivolumab and chemoradiotherapy may work better in treating patients with stage II-IVB nasopharyngeal cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To establish the feasibility of treatment completion of a combined
      chemoradiation-nivolumab regimen followed by adjuvant nivolumab.

      SECONDARY OBJECTIVES:

      I. To determine the overall response rate at 1 year from completion of therapy, as determined
      by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

      II. To determine the locoregional control rate at 1 year post-treatment. III. To determine
      the distant metastasis rate at 1 year post-treatment. IV. To determine the overall survival
      rate at 1 year post-treatment. V. To determine the rate of Epstein-Barr virus (EBV)
      deoxyribonucleic acid (DNA) clearance at end of chemoradiation and at 1 year post-treatment.

      VI. To assess patients' quality of life from baseline through 1 year post-treatment.

      VII. To determine the acute and late toxicity rates according to Common Terminology Criteria
      for Adverse Events (CTCAE) version (v.) 5, including immune-related adverse events (AEs).

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 60 minutes on day 1 of courses 1-5 and
      7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or
      unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy once daily
      (QD) 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats
      every 7 days for up to 3 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 100 days, at 1, 3, 6, 9,
      and 12 months for up to 1 year, and then every 3 months for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + chemoradiationExperimentalPatients receive nivolumab IV over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy QD 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Males and females ≥18 years of age.

          2. Histologically or cytologically confirmed nasopharyngeal carcinoma, stage II-IV by
             American Joint Committee on Cancer (AJCC) 7th edition, endemic-type (defined as World
             Health Organization (WHO) type 2a and 2b nonkeratinizing or undifferentiated subtypes,
             excluding WHO type I keratinizing subtype) performed on a biopsy that occurred within
             90 days of registration.

          3. Positron emission tomography-computed tomography (PET-CT) (preferred) or a CT of
             chest, abdomen, and pelvis within 60 days of registration showing radiographic stage
             II to IVB nasopharyngeal cancer.

          4. No distant metastasis as verified by one of the study investigators.

          5. Documentation that the patient is a candidate for chemoradiation of their
             nasopharyngeal cancer by one of the study investigators.

          6. Ability to tolerate radiation therapy (e.g. lie flat and hold position for treatment).

          7. Measurable disease as defined by RECIST v1.1.

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          9. Lack of contraindications to systemic immunotherapy (see list of exclusions below).

         10. Resolution of all acute toxic effects of any prior chemotherapy, radiotherapy or
             surgical procedures to NCI CTCAE Version 4.0 grade 1.

         11. Adequate hepatic, hematologic, and renal indices permitting administration of
             cisplatin and nivolumab (within 14 days of registration):

             Hepatic Function:

             Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit
             of normal (ULN); Total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert Syndrome,
             who can have total bilirubin < 3.0 mg/dL)

             Adequate bone marrow function:

             White blood cells (WBC) ≥ 2000/μL Neutrophils ≥ 1500/μL Platelet ≥ 100 x103/μL
             Hemoglobin > 9.0 g/dL

             Adequate renal function:

             Serum creatinine ≤ 1.5 × upper limit of normal (ULN) OR Creatinine clearance (CrCl) >
             40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in
             years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in
             years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

         12. Women of childbearing potential must have a negative serum pregnancy test within 24
             hours prior to the first dose of study treatment and agree to use appropriate highly
             effective methods of contraception, during the study and for 5 months following
             completion of study treatment; A "Woman of childbearing potential" is defined as any
             female who has experienced menarche and who has not undergone surgical sterilization
             (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is
             defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of
             other biological or physiological causes. In addition, women under the age of 62 must
             have a documented serum follicle stimulating hormone (FSH) level less than 40
             milli-international units per milliliter (mIU/mL).

             Female Subjects:

             Women of child bearing potential are expected to use one of the highly effective
             methods of contraception listed in the protocol.

             Male Subjects:

             Male subjects must inform their female partners who are women of child bearing
             potential of the contraceptive requirements and are expected to adhere to using
             contraception with their partner. Female partners of male subjects, who are women of
             child bearing potential, are expected to use one of the highly effective methods of
             contraception listed in the protocol. In addition, male subjects are expected to use a
             condom as noted in the protocol.

         13. Men with a female partner of childbearing potential must agree to use highly effective
             methods of contraception or any contraceptive method with a failure rate of less than
             1% per year during the study and for 7 months following completion of study treatment.

         14. Ability to sign informed consent.

        Exclusion Criteria:

          1. Active second malignancy, i.e. patient known to have potentially fatal hematologic
             malignancy or another solid primary tumor present for which he/she may be (but not
             necessarily) currently receiving treatment. Patients with a prior or concurrent
             malignancy whose natural history or treatment does not have the potential to interfere
             with the safety or efficacy assessment of the investigational regimen are allowed to
             enroll in this trial. For example, patients with early-stage skin cancers, prostate
             cancer under surveillance with non-rising prostate-specific antigen (PSA), or
             meningioma or thyroid papillary cancers which are under surveillance are eligible. For
             determinations of a specific clinical condition, please consult with the Principal
             Investigator.

          2. Active, untreated central nervous system (CNS) metastases;

          3. Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD
             Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2), anti-cytotoxic T-lymphocyte-associated
             protein-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting
             T-cell costimulation or immune checkpoint pathways, or cancer vaccine;

          4. Prior systemic cytotoxic therapy, antineoplastic biologic therapy, or major surgery
             within 28 days of first dose of study medication;

          5. Severe hypersensitivity reaction to treatment during prior administration of a
             monoclonal antibody (mAb) or history of allergy to any study drug component;

          6. Has received a live-virus vaccination within 30 days of planned treatment start;

          7. Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days of study
             drug administration; Inhaled or topical steroids and adrenal replacement doses > 10 mg
             daily prednisone equivalents are permitted in the absence of active autoimmune
             disease.

          8. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior
             history of ILD or pneumonitis requiring oral or IV glucocorticoids;

          9. Active, known, or suspected autoimmune disease or any autoimmune condition that has
             required systemic treatment in the past 2 years (replacement therapies for hormone
             deficiencies are allowed); Subjects are permitted to enroll if they have vitiligo,
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger.

         10. Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI)
             obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation);

         11. Signs or symptoms of infection within 2 weeks prior to first day of study treatment.

         12. Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study
             treatment:

             Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection
             or chronic obstructive pulmonary disease exacerbation) are eligible.

         13. Known positive test for human immunodeficiency virus (HIV);

         14. Known active hepatitis B or hepatitis C virus (HBV or HCV):

             Patients with past or resolved HBV infection (defined by a negative hepatitis B
             surface antigen [HBsAg] test and a positive anti-hepatitis B core antigen (HBc)
             antibody test) are eligible. HBV DNA must be obtained in these patients prior to first
             day of study treatment.

             Patients who have been recently discovered to have HBV with positive HBsAg test and
             positive anti HBc antibody test but who have been started on antiretroviral treatment
             with nondetectable HBV DNA are eligible. HBV DNA must be obtained in these patients
             prior to first day of study treatment.

         15. Patients with known active hepatitis C virus ribonucleic acid (HCV antibody)
             indicating acute or chronic infection:

             Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.

         16. Prior radiation therapy of any type within 7 days of first dose of study medication;

         17. Prior radiation therapy to head and neck region that would overlap with intended
             radiation treatment for nasopharyngeal carcinoma;

         18. Medical contraindication to radiation treatment (e.g. active systemic sclerosis, other
             uncontrolled autoimmune condition)

         19. Treatment with prohibited medications (including concurrent anticancer therapy
             including chemotherapy, radiation, hormonal treatment [except corticosteroids and
             megestrol acetate] ≤ 14 days prior to treatment.

         20. Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study;

         21. Active, uncontrolled psychiatric disorders or substance (drug/alcohol) abuse that
             interfere with patient's safety, ability to provide informed consent, or ability to
             comply with the protocol.

         22. Persons who are incarcerated or otherwise under compulsory detention by an authority
             are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of treatment completion: Rate of completion of all adjuvant immunotherapy, in comparison to the rate of completion of a standard adjuvant cisplatin-based platform.
Time Frame:Through study completion, maximum of 1 year
Safety Issue:
Description:The rate of completion of all adjuvant therapy by patients treated at the maximum tolerated dose (MTD) schedule will be determined and compared to a historical control rate of 52%.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:From baseline to up to 1 year after completion of treatment
Safety Issue:
Description:As determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The ORR is defined as the best overall response (BOR) recorded from the first day of treatment until time of assessment.
Measure:Number and frequency of Adverse Events (AEs)
Time Frame:From baseline to up to 1 year after completion of treatment
Safety Issue:
Description:As determined by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0 by investigator assessment
Measure:Locoregional Control (LRC) Rate
Time Frame:From first day of treatment to time of documented relapse, progression or death up to 1 year after completion of treatment
Safety Issue:
Description:Duration of LRC will be calculated as 1+ the number of days from the first day of treatment to time of documented locoregional clinical or radiographic relapse, progression or death due to any cause.
Measure:Distant Metastasis (DM) Rate
Time Frame:From first day of treatment to time of documented progression at a distant metastatic site, or death up to 1 year after completion of treatment
Safety Issue:
Description:Time to DM will be calculated as 1+ the number of days from the first day of treatment to documented clinical or radiographic progression at a distant metastatic site, or death due to any cause.
Measure:Overall survival rate (OSR)
Time Frame:From baseline to up to 1 year after completion of treatment
Safety Issue:
Description:As determined by standard physical examination and radiologic imaging
Measure:Rate of Epstein-Barr Virus (EBV) DNA clearance
Time Frame:Through study completion, maximum of 1 year
Safety Issue:
Description:From plasma by standardized polymerase chain reaction (PCR) assay
Measure:Quality of life as assessed by patient reported outcomes
Time Frame:From baseline to up to 1 year after completion of treatment
Safety Issue:
Description:Measured by Functional Assessment of Cancer Therapy - Nasopharyngeal Cancer (FACT-NP)
Measure:Acute and late toxicity rates according to CTCAE version 5, including immune-related AEs
Time Frame:Up to 1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

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