Porfimer Sodium Interstitial Photodynamic Therapy With or Without Standard of Care Chemotherapy in Treating Patients With Locally Advanced or Recurrent Head and Neck Cancer

PRIMARY OBJECTIVES:

I. To determine the safety of adjuvant porfimer sodium (Photofrin) mediated interstitial
photodynamic therapy (I-PDT) in patients with locally advanced or recurrent head and neck
cancer (HNC) who will receive chemotherapy (cisplatin or carboplatin and fluorouracil [5-FU])
and/or targeted agents (cetuximab), and/or immunotherapy (nivolumab, or pembrolizumab), i.e.
standard of care (SoC) therapy. (Phase I) II. To evaluate the efficacy of adjuvant porfimer
sodium mediated I-PDT with SoC therapy by comparing the objective tumor response rate of a
locally advanced HNC treated with I-PDT with SoC to SoC therapy alone, in patients with
locally advanced or recurrent HNC. (Phase II)

EXPLORATORY OBJECTIVES:

I. To compare progression free survival (PFS) and overall survival (OS) between adjuvant
porfimer sodium mediated I-PDT with SoC therapy and SoC alone, in patients with locally
advanced or recurrent HNC. (Phase II) II. To compare changes in quality of life (QoL) between
adjuvant porfimer sodium mediated I-PDT with SoC therapy and SoC alone, in patients with
locally advanced or recurrent HNC. (Phase II) III. To evaluate the relationship between
response rate and immune markers in patients with locally advanced or recurrent HNC receiving
either adjuvant porfimer sodium mediated I-PDT with SoC therapy or SoC alone. (Phase II) IV.
To evaluate the relationship between objective response rate and levels of serum alkaline
deoxyribonuclease (DNase) activity (SADA), a circulating biomarker, in patients with locally
advanced or recurrent HNC receiving either adjuvant porfimer sodium mediated I-PDT with SoC
therapy or SoC alone. (Phase II)

OUTLINE: This is a phase I study followed by a phase II study.

PHASE I: Patients receive porfimer sodium intravenously (IV) over 3-5 minutes and undergo
I-PDT approximately 48 hours later. Patients also receive SoC chemotherapy (cisplatin,
carboplatin, fluorouracil, cetuximab, nivolumab, pembrolizumab) at the oncologist's
discretion at either 7 days, 14 days, or 28 days later.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive SoC chemotherapy (cisplatin, carboplatin, fluorouracil, cetuximab,
nivolumab, pembrolizumab) at the oncologist's discretion.

ARM B: Patients receive porfimer sodium IV over 3-5 minutes and undergo I-PDT approximately
48 hours later. Patients also receive SoC chemotherapy (cisplatin, carboplatin, fluorouracil,
cetuximab, nivolumab, pembrolizumab) at the oncologist's discretion at either 7 days, 14
days, or 28 days later.

After completion of study treatment, patients are followed up at 30 days, 1-3 months for 1
year, 2-6 months for 1 year, and annually up to 5 years.

Inclusion Criteria:

- Subjects must have an Eastern Cooperative Oncology Group (ECOG) scale of 0-2.

- Patients with locally advanced or recurrent head and neck cancer who failed to respond
to standard therapy and are not amenable to standard curative treatment.

- Tumor accessible for unrestricted illumination for interstitial photodynamic therapy
(PDT) (accessibility as determined by the physician).

- Patients are scheduled to receive chemotherapy and/or targeted agents, and/or
immunotherapy.

- Life expectancy of at least 6 months, in the judgment of the physician.

- Subjects of child-bearing potential must agree to use adequate contraceptive methods
(e.g., hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately.

- Subject or legal representative must understand the investigational nature of this
study and sign an Institutional Review Board approved written informed consent form
prior to receiving any study related procedure.

Exclusion Criteria:

- Radiotherapy within 30 days in the area to be treated. Tumor invading a major blood
vessel.

- Tumor is not measurable on a computed tomography (CT) or magnetic resonance imaging
(MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

- Location and extension of the tumor precludes a potentially effective I-PDT.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

- Patients with porphyria, or with known hypersensitivity to porphyrins or
porphyrin-like compounds.

- Platelet count < 75,000.

- Total serum bilirubin > 2 mg/dL

- Alkaline phosphatase (hepatic) > 3 times the upper normal limit

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
transaminase (SGPT) > 3 times the upper normal limit

- Patients with moderately to severely impaired creatinine clearance (crcl < 44) will be
excluded.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant or nursing female subjects.

- Unwilling or unable to follow protocol requirements.

- Any condition which in the investigator's opinion deems the subject an unsuitable
candidate to receive porfimer sodium