Clinical Trials /

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

NCT03727061

Description:

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.

Related Conditions:
  • Head and Neck Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Porfimer Sodium Interstitial Photodynamic Therapy With or Without Standard of Care Chemotherapy in Treating Patients With Locally Advanced or Recurrent Head and Neck Cancer
  • Official Title: A Randomized, Multi-Center 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

Clinical Trial IDs

  • ORG STUDY ID: I 67918
  • SECONDARY ID: R01CA193610
  • SECONDARY ID: P30CA016056
  • SECONDARY ID: P01CA055791
  • NCT ID: NCT03727061

Conditions

  • Recurrent Head and Neck Carcinoma
  • Locally Advanced Head and Neck Carcinoma

Interventions

DrugSynonymsArms
NivolumabNIVO, NIVOLUMAB, Nivolumab, BMS-936558Arm A (standard of care chemotherapy at doctor's discretion)
Porfimer SodiumPhotofrin II, Photofrin II, PORFIMER SODIUM, porfimer sodium, Porfimer SodiumArm B(porfimer sodium, I-PDT, SoC chemotherapy)
PembrolizumabArm A (standard of care chemotherapy at doctor's discretion)
CisplatinPlatinolArm A (standard of care chemotherapy at doctor's discretion)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino,Arm A (standard of care chemotherapy at doctor's discretion)
CetuximabCetuximab Biosimilar CMAB009,Arm A (standard of care chemotherapy at doctor's discretion)
Fluorouracil5-Fluorouracil, 5-Fluracil, 5-FUArm A (standard of care chemotherapy at doctor's discretion)

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (standard of care chemotherapy at doctor's discretion)Active ComparatorPatients receive SoC chemotherapy (cisplatin, carboplatin, fluorouracil, cetuximab, nivolumab, pembrolizumab) at the oncologist's discretion
  • Nivolumab
  • Pembrolizumab
  • Cisplatin
  • Carboplatin
  • Cetuximab
  • Fluorouracil
Arm B(porfimer sodium, I-PDT, SoC chemotherapy)ExperimentalPatients 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.
  • Nivolumab
  • Porfimer Sodium
  • Pembrolizumab
  • Cisplatin
  • Carboplatin
  • Cetuximab
  • Fluorouracil

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)
Time Frame:Up to 30 days
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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