A Study of Radiation Therapy With Experimental Durvalumab or Cetuximab For Head and Neck Cancer Who Cannot Take Cisplatin

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 18 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: head and neck cancer, head cancer, neck cancer, stage iii head and neck cancer, stage IVb head and neck cancer
Type: Biological study, Phase [/2/,/ /3/]
Target:
12 Participants
Investigator:
Description
This study will test the effects of radiation plus the experimental study treatment, MEDI4736 (durvalumab). It will be compared to the usual therapy of radiation plus cetuximab. The study is for patients with head and neck cancer who cannot take the drug cisplatin.

MEDI4736 works by boosting your immune system to help recognize and fight cancer. MEDI4736 is FDA-approved for cancer of the urinary system. It is not approved for use with radiation therapy in head and neck cancer.

The study treatment may or may not shrink your cancer, but it could also cause side effects. This study will allow the researchers to know whether this different approach (radiation and MEDI4736) is better, the same, or worse than the usual approach.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  • PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA
  • Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary within 60 days prior to step 1 registration; submission of hematoxylin and eosin (H&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch biopsy of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H&E and p16 stained slides to the biospecimen bank at UCSF for central review is also required prior to step 2 registration
  • Note: fine needle aspirates (FNA) samples are not acceptable since they do not provide enough material for PD-L1 and p16 testing
  • Patients must have locoregionally advanced head and neck squamous cell carcinoma (HNSCC)
  • For p16-positive oropharyngeal/unknown primaries, American Joint Committee on Cancer [AJCC] 8th edition stage III and selected stage I-II based on smoking status in pack-years
  • For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB
  • Based on the following minimum diagnostic workup within 60 days prior to step 1 registration:
  • General history and physical examination by a radiation oncologist or medical oncologist or ear, nose and throat (ENT) or head & neck surgeon
  • For larynx, hypopharynx, and base of tongue primaries, a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is required, unless the patient cannot tolerate or refuses
  • Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI) (with contrast, unless contraindicated) or PET/CT; note that the CT portion of the PET/CT must be of diagnostic quality, including contrast administration unless contraindicated. If the CT portion of the PET/CT study is low-dose (non-diagnostic), then an additional CT or MRI study with contrast (unless contraindicated) is required
  • Chest imaging: chest CT with and without contrast (unless contraindicated) or PET/CT
  • Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF)
  • Age >= 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having any one or more of the following conditions within 30 days prior to step 1 registration:
  • Modified Charlson Comorbidity Index >= 1
  • Adult Comorbidity Evaluation (ACE)-27 Index >= 1
  • Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score < 0.60
  • Geriatric screening (G-8) score =< 14
  • Cancer and Aging Research Group (CARG) toxicity score >= 30%
  • Cumulative Illness Rating scale for Geriatrics (CIRS-G) score >= 4 OR
  • Age < 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 30 days prior to step 1 registration
  • Modified Charlson Comorbidity Index >= 1
  • ACE-27 Index >= 1
  • GCE omega PFS-score < 0.60
  • G-8 score =< 14
  • CARG Toxicity score >= 30%
  • CIRS-G score >= 4 OR
  • Age >= 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following within 30 days prior to step 1 registration:
  • Creatinine clearance (CC) > 30 and < 60 cc/min; for this calculation, use the Cockcroft-Gault formula
  • Zubrod performance status 2 prior to step 1 registration
  • Pre-existing peripheral neuropathy grade >= 1
  • History of hearing loss, defined as either:
  • Existing need of a hearing aid OR
  • = 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test

  • Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 14 days prior to step 1 registration)
  • Platelets >= 100,000 cells/mm^3 (within 14 days prior to step 1 registration)
  • Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable) (within 14 days prior to step 1 registration)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times institutional upper limit of normal (within 14 days prior to step 1 registration)
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (within 14 days prior to step 1 registration)
  • Measured creatinine clearance (CL) > 30 mL/min or calculated creatinine CL > 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (within 14 days prior to step 1 registration)
  • For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:
  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
  • PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA
  • For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review
  • Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries, analysis of p16 status prior to step 2 registration/randomization is not required (p16 status will be analyzed centrally post-hoc); step 2 registration for these patients can be completed after step 1 registration

Exclusion criteria:

  • PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA
  • Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer)
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Prior immunotherapy
  • Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
  • Major surgery within 28 days prior to step 1 registration
  • Proven evidence of distant metastases
  • If both of the following conditions are present, the patient is ineligible:
  • =< 10 pack-year smoking history
  • p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition)
  • Note: in the event that a registered patient with =< 10 pack-years has a p16-positive result on central review with the tumor and nodal stage T0-3, N0-1 (AJCC 8th Edition), then the site will be notified that the patient is ineligible
  • Zubrod performance status >= 3
  • Body weight =< 30 kg
  • Patients with oral cavity cancer are excluded from participation if the patient is medically operable and resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist;(please consult the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine [MD], if clarification is needed on an individual case)
  • Sodium < 130 mmol/L or > 155 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Potassium < 3.5 mmol/L or > 6 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Fasting glucose < 40 mg/dl or > 400 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Magnesium < 0.9 mg/dl or > 3 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registration
  • Transmural myocardial infarction within 3 months prior to step 1 registration
  • Respiratory illness requiring hospitalization at the time of step 1 registration
  • Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
  • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Clinically apparent jaundice and/or known coagulation defects
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.])
  • The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia;
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
  • Any chronic skin condition that does not require systemic therapy;
  • Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair;
  • Patients with celiac disease controlled by diet alone
  • History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive; patients with known HIV, CD4 counts >= 200/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included
  • Current or prior use of immunosuppressive medication within 14 days before step 1 registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • Receipt of live attenuated vaccination within 30 days prior to step 1 registration
  • Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic; women who are breastfeeding are also excluded
  • Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients
  • History of allogenic organ transplantation
  • Uncontrolled hypertension
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled serious chronic gastrointestinal condition associated with diarrhea
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
If you are in Group 1, you will receive 1 dose of cetuximab 1 week before you start radiation. You will then have radiation plus weekly cetuximab for 7 weeks. If you are in Group 2, you will receive MEDI14736 every 4 weeks for 24 to 32 weeks. Then, radiation for 7 weeks beginning 2 weeks after your first MED14736 dose. After you finish treatment, your doctor will continue to watch you for side effects. The team will follow your condition every 4 months for 1 year, every 6 months for 2 years, then every year.
Recruitment period
From Sept. 11, 2018
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Unknown Primary Origin
  • Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7
  • Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7

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