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Summary

for people ages 18 years and up (full criteria)
study started
estimated completion:

Description

Summary

This is a Phase 2, single arm, open-label, multicenter study evaluating the feasibility of a treatment regimen comprised of nivolumab administered approximately every 2 weeks before and during chemoradiation and as an adjuvant therapy for 3 months to patients with stage II-IVB NPC who are planning to undergo chemoradiation treatment of their cancer.

Official Title

Nivolumab in Combination With Chemoradiation for Patients With Stage II-IVB Nasopharyngeal Carcinoma, A Phase II Study With Correlative Biomarkers

Details

A run-in phase will precede expansion, to establish basic feasibility of the nivolumab with chemoradiation schedule. The run-in cohorts will include 6 patients at each dose schedule, with 2 planned changes in dose schedule if >33% toxicity or other dose limiting toxicity (DLT) is observed. A minimum of 6 patients and maximum of 18 patients may be enrolled in the three run-in cohorts. The maximum tolerated dose (MTD) schedule will be selected when 4/6 patients at a dose schedule complete therapy without grade 3-4 immune related toxicity. All patients will receive the same dose of nivolumab (240mg).

The expansion phase will continue after the run-in phase has been used to establish the MTD schedule for nivolumab. The expansion phase will be powered to test the feasibility of completion of the program as compared to the current standard of care.

Keywords

Nasopharyngeal Carcinoma Carcinoma Nasopharyngeal Neoplasms Nivolumab Cisplatin Antibodies, Monoclonal

Eligibility

You can join if…

Open to people ages 18 years and up

  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) 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

  1. . 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.

  1. . 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.
  2. . Ability to sign informed consent.

You CAN'T join if...

  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 history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided treatment was completed >2 years prior. Patients with early-stage skin cancers and prostate cancer under surveillance with non-rising prostate specific antigen (PSA) are eligible.
  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.

  1. . Known positive test for human immunodeficiency virus (HIV);
  2. . 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.

  1. . 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.

  1. . Prior radiation therapy of any type within 7 days of first dose of study medication;
  2. . Prior radiation therapy to head and neck region that would overlap with intended radiation treatment for nasopharyngeal carcinoma;
  3. . Medical contraindication to radiation treatment (e.g. active systemic sclerosis, other uncontrolled autoimmune condition)
  4. . Treatment with prohibited medications (including concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megestrol acetate] ≤ 14 days prior to treatment.
  5. . Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study;
  6. . 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.
  7. . Persons who are incarcerated or otherwise under compulsory detention by an authority are not eligible.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03267498
Phase
Phase 2
Lead Scientist
Sue S Yom
Study Type
Interventional
Last Updated
October 30, 2017
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