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

Study Overview
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Brief Summary
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This phase I/II trial studies the side effects of interstitial photodynamic therapy and to see how well it works with standard of care chemotherapy in treating patients with head and neck cancer that has spread to other parts of the body or that has come back. Interstitial photodynamic therapy uses a light-sensitive drug called porfimer sodium. This drug is activated by laser light delivered through special fibers into the tumor. It is not yet known how well porfimer sodium interstitial photodynamic therapy works, with or without standard of care chemotherapy, in treating patients with head and neck cancer.

Detailed Description
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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 standard of care (SoC) therapy that includes: 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 and or other clinically approved treatment for the disease management such as: other chemotherapy, reirradiation or palliative treatment for pain control. (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.

Official Title
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A Randomized, Phase 2 Trial With a Phase 1 Safety Run-in: Porfimer Sodium Mediated Interstitial Photodynamic Therapy and Standard of Care (SoC) Therapy Versus SoC Therapy Alone for the Treatment of Patients With Locally Advanced or Recurrent Head and Neck Cancer

Conditions
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Recurrent Head and Neck Carcinoma, Locally Advanced Head and Neck Carcinoma

Intervention / Treatment
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* Biological: Nivolumab
* Drug: Porfimer Sodium
* Procedure: Interstitial Illumination Photodynamic Therapy
* Biological: Pembrolizumab
* Drug: Cisplatin
* Drug: Carboplatin
* Biological: Cetuximab
* Other: Quality of Life Assessment
* Drug: Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score 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 candidates to receive chemotherapy and/or targeted agents, and/or immunotherapy and/or clinically approved treatment for the disease management such as: other chemotherapy, reirradiation or palliative treatment for pain control. 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A (standard of care chemotherapy at doctor's discretion)<br>Patients receive SoC chemotherapy (cisplatin, carboplatin, fluorouracil, cetuximab, nivolumab, pembrolizumab) at the oncologist's discretion | Biological: Nivolumab<br>* Immunotherapy - Standard of care<br>* Other names: NIVO, NIVOLUMAB, Nivolumab, BMS-936558;Biological: Pembrolizumab<br>* Immunotherapy - Standard of care<br>Drug: Cisplatin<br>* Standard of Care<br>* Other names: Platinol;Drug: Carboplatin<br>* Standard of Care<br>* Other names: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino,;Biological: Cetuximab<br>* Standard of Care<br>* Other names: Cetuximab Biosimilar CMAB009,;Other: Quality of Life Assessment<br>* Ancillary Studies<br>Drug: Fluorouracil<br>* Standard of Care<br>* Other names: 5-Fluorouracil, 5-Fluracil, 5-FU;|
| Experimental: Arm B(porfimer sodium, I-PDT, SoC chemotherapy)<br>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. | Biological: Nivolumab<br>* Immunotherapy - Standard of care<br>* Other names: NIVO, NIVOLUMAB, Nivolumab, BMS-936558;Drug: Porfimer Sodium<br>* Given IV<br>* Other names: Photofrin II, Photofrin II, PORFIMER SODIUM, porfimer sodium, Porfimer Sodium;Procedure: Interstitial Illumination Photodynamic Therapy<br>* Undergo I-PDT<br>Biological: Pembrolizumab<br>* Immunotherapy - Standard of care<br>Drug: Cisplatin<br>* Standard of Care<br>* Other names: Platinol;Drug: Carboplatin<br>* Standard of Care<br>* Other names: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino,;Biological: Cetuximab<br>* Standard of Care<br>* Other names: Cetuximab Biosimilar CMAB009,;Other: Quality of Life Assessment<br>* Ancillary Studies<br>Drug: Fluorouracil<br>* Standard of Care<br>* Other names: 5-Fluorouracil, 5-Fluracil, 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I) | The frequency of toxicities will be tabulated by grade across all dose levels and cycles. All subjects who receive any study treatment will be considered evaluable for toxicity. Sequential boundaries will be used to monitor the serious adverse event (SAE) rate. | Up to 30 days | 
| Objective target tumor response rates (Phase II) | Will compare locally advanced head and neck cancer (HNC) treated with interstitial photodynamic therapy (I-PDT) followed by standard of care (SoC) to the ones treated with SoC alone. Fisher's exact test will be used for the primary analysis of objective tumor response rates at 10-12 weeks. The primary analysis will be intention-to-treat. | At 10-12 weeks |