Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma
Condition: Carcinoma, Squamous Cell; Oral Cancer; Oropharynx Cancer; Larynx Cancer; Lip Cancer; Esophageal Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Lip Neoplasms
Intervention: Durvalumab; Carboplatin; Nab-paclitaxel; Cisplatin; Surgical resection; IMRT
Intervention description: Subjects will receive durvalumab, 750 mg every 2 weeks by IV infusion over approximately 1 hour (± 5 minutes).; Carboplatin is commercially available and approved by the US FDA for use in patients with ovarian cancer.; Nab-paclitaxel is commercially available and approved by the US Food and Drug Administration (FDA) for use in patients with metastatic breast cancer, metastatic pancreatic cancer, and for the treatment of locally advanced or metastatic NSCLC.; Cisplatin is commercially available and approved by the US Food and Drug Administration (FDA) for the treatment of advanced bladder, ovarian and testicular cancer. It has been widely studied in a variety of solid tumor types.; Surgical therapy will be at the discretion of the treating surgeon per standard of care.; "involved field radiation" will refer to areas demonstrated to harbor disease on pathology, and not elective areas
Intervention MeSH terms: Paclitaxel; Carboplatin; Durvalumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma of the head and neck (SCCHN); durvalumab; neoadjuvant induction; post-operative treatment

Summary:

      Participants in this study have a type of cancer called squamous cell carcinoma of the head
      and neck (SCCHN). Their SCCHN has spread around the area where the cancer first started. This
      is called locally-advanced SCCHN. These participants are eligible for surgery.

      Previous research with a similar therapy regimen resulted in high rates of cancer shrinkage,
      high rates of avoiding radiation and its side effects, high cure rate and good quality of
      life. Radiation can be very toxic. The purpose on this study is to try to avoid radiation. If
      the participants are not on this study they would be receiving radiation as it is standard
      treatment of their cancer. In the last study with a similar regimen, about a third of cancers
      had a pathologic complete response with the first part of the study. This means that the
      chemotherapy had killed the cancer. The investigators are trying to improve the regimen
      further with a goal of increasing this rate of complete response to the first part of
      therapy. The investigators also hope that by improving results in the first part, that more
      people will be cured and that long term quality of life (especially speech and swallowing)
      will be improved, both compared to standard therapies and to the last study. Doctors do not
      know how this therapy will effect the participants. There is no guarantee that this study
      will benefit the participants.

      The prior study used a combination of chemotherapy consisting of carboplatin, paclitaxel and
      a third targeted anti-cancer drug. In this study the investigators are testing the
      combination of carboplatin, nano-albumin bound paclitaxel and durvalumab. Nano-albumin bound
      paclitaxel has been shown to be more active against other types of squamous cancers than
      regular paclitaxel. It is FDA approved for squamous lung cancer, but experimental for head
      and neck cancer. Durvalumab is an experimental drug that uses the body's own immune system to
      fight the cancer. Doctors hope that combining Durvalumab with 2 chemotherapy drugs will be
      effective in treating SCCHN. Durvalumab on its own has been studied in patients with SCCHN
      and initial results have shown that some subjects' cancer has responded to it.

      The purpose of this study is to test a combination of chemotherapy to hopefully both increase
      the number of subjects that respond to therapy while also decreasing the number of side
      effects that subjects experience.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated, histologically proven, surgically resectable primary squamous
             cell carinoma of the head and neck, stage III or IV (HPV positive or negative
             non-metastatic disease). SCCHN of unknown primary is excluded. SCCHN of the oral
             cavity is allowed*. Unambiguously squamous Epstein-Barr virus (EBV)-negative
             nasopharynx cancer will be excluded nor will unambiguously squamous cancers of the
             skull base that are clearly surgically resectable and clearly squamous. Squamous skin
             cancer occurring in the head/neck region will not be eligible nor will EBV+positive
             nasopharynx cancer. (*Note: Induction chemotherapy is not considered standard therapy
             for SCCHN of the oral cavity and participation on this trial will lead to a delay in
             time to definitive, potentially curative therapy i.e., surgery).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Measurable disease as per RECIST 1.1

          -  Age greater than or equal to 18 at time of study entry

          -  Adequate bone marrow function as demonstrated by:

               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

               -  Hgb > 10 g/dL (use of transfusion to reach this threshold prior to study
                  initiation is acceptable)

               -  Platelet count ≥ 100,000/mm3

          -  Adequate hepatic and renal function as demonstrated by:

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper
                  limit of normal (ULN);

               -  Total serum bilirubin ≤1.5 x ULN

               -  Creatinine clearance (CrCL) > 40 mL/min as measured via Cockcroft-Gault

                    -  Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum
                       creatinine (mg/dL))

                    -  Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum
                       creatinine (mg/dL)) x 0.85

          -  Negative serum β human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours
             of day 1 of induction chemotherapy in women of child-bearing potential.

          -  All males and females of childbearing potential must agree to use adequate
             contraception during the study. Adequate contraception is defined as any medically
             recommended method (or combination of methods) as per standard of care. Females of
             non-childbearing potential are those who are postmenopausal greater than 1 year or who
             have had a bilateral tubal ligation or hysterectomy or bilateral oophorectomy. See
             section 4.13 for list of acceptable methods of contraception.

          -  Signed an institutional review board (IRB)-approved informed consent and HIPAA
             authorization.

          -  Subject is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

          -  Subjects must agree to allow use of any pre-treatment tissue remaining after
             definitive diagnosis is made (ie, archival and or fresh tissue) for research purposes.
             In addition, subjects must consent to allow use of their residual post-operative
             tissue for research purposes.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to staff at the study
             site) or previous enrollment in the present study.

          -  Any metastatic disease.

          -  Known history of previous clinical diagnosis of tuberculosis.

          -  History and/or confirmed pneumonitis.

          -  Low-risk HPV+ disease of the oropharynx, defined as meeting all of the following
             criteria:

               -  Patients with known HPV+ by fluorescence in situ hybridization (FISH) and/or p16

               -  Smoking history ≤ 10 pack years

               -  Stage T1-2N0-2b, T3N0

          -  Not considered eligible for any of the chemotherapy agents included in the induction
             regimen.

          -  Current active hepatic or biliary disease (with exception of patients with Gilbert's
             syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator
             assessment).

          -  Major surgery within 28 days prior to day 1 of study treatment from which the patient
             has not completely recovered.

          -  Receiving any investigational agent currently or within 28 days or 5 half-lives of Day
             1 of treatment on this study, whichever is shorter.

          -  Active, serious infection, medical, or psychiatric condition that would represent an
             inappropriate risk to the patient or would likely compromise achievement of the
             primary study objective, including unstable angina, serious uncontrolled cardiac
             arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6 months prior to study
             entry.

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis with the
             exception of a prior episode that has resolved or diverticulosis, celiac disease,
             irritable bowel disease, or other serious gastrointestinal chronic conditions
             associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome
             [granulomatosis with polyangiitis]; myasthenia gravis;; rheumatoid arthritis;
             hypophysitis, uveitis; etc) within the past 2 years prior to the start of treatment.
             [Note: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic
             treatment (within the past 2 years) are not excluded]

          -  Known mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs) using Frediricia's Correction. (Note that ECG is not
             required for study entry and is not part of study procedures).

          -  Other prior or concomitant malignancies with the exception of:

               -  Non-melanoma skin cancer

               -  In-situ malignancy

               -  Low-risk prostate cancer after curative therapy

               -  Other cancer for which the patient has been disease free for ≥ 5 years before the
                  first dose of study drug and of low potential risk for recurrence.

          -  Any concurrent chemotherapy, investigational product, biologic or hormonal therapy for
             cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
             (e.g. hormone replacement therapy) is acceptable.

          -  Current or prior use of immunosuppressive medication within 14 days prior to the first
             dose of durvalumab. The following are exceptions to this criterion: intranasal,
             inhaled, topical or local steroid injections (eg. intra-articular injection); steroids
             as premedication for hypersensitivity reactions; systemic corticosteroid at
             physiologic doses not to exceed 10mg/day of prednisone or equivalent.[Note: If
             systemic corticosteroids are part of the treatment regimen for the indication under
             study, the systemic corticosteroid is permitted].

          -  Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of
             active hepatitis B virus (HBV).

          -  History of hypersensitivity to durvalumab or any excipient.

          -  Receipt of live attenuated vaccination within 30 days prior the first dose of
             durvalumab [Note: If a vaccine is part of the treatment regimen for the indication
             under study, the vaccine is permitted].

          -  Female subjects who are pregnant, breast-feeding or female patients of reproductive
             potential who are not employing an effective method of birth control from starting
             dose of study medications (Cycle 1 Day 1), including dosing interruptions through 90
             days after receipt of the last dose of durvalumab. Refrain from egg cell donation
             while taking durvalumab and for at least 90 days after the last dose of durvalumab.

          -  Male subjects who are not employing an effective method of birth control from starting
             dose of study medications (Cycle 1 Day 1), including dosing interruptions through 6
             months after receipt of study treatment. Male subjects should agree to refrain from
             sperm donation while taking study treatment and for at least 6 months after the last
             dose of nab-paclitaxel and at least 90 days after the last dose of durvalumab. Should
             a female partner of a male patient become pregnant or suspect she is pregnant while
             participating in the study, he should inform his treating physician and the female
             partner should call her physician immediately.

          -  Any previous treatment with a programmed cell death protein 1 (PD-1) or programmed
             death-ligand 1 (PD-L1) inhibitor, including durvalumab.

          -  History of primary immunodeficiency.

          -  History of organ transplant.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results
             (eg, uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, uncontrolled hypertension,
             unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or
             gastritis, active bleeding diatheses or psychiatric illness/social situations that
             would limit compliance with study requirements or compromise the ability of the
             subject to give written informed consent).

          -  Patients with known contraindications to radiotherapy including inherited syndromes
             associated with hypersensitivity to ionizing radiation (e.g., Ataxia Telangiectasia,
             Nijmegen Breakage Syndrome).