Clinical Trials /

Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Platin, 5-FU, Cetuximab, and Taxane

NCT02369458

Description:

No agent is known to have efficacy in patients with incurable HNSCC that progressed with prior platin, 5-FU, cetuximab and taxane. Herein lies the unmet need to be addressed by this trial. Based on the preclinical and clinical data presented, the investigators propose that mitomycin C will have anti-tumor activity in these patients.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Platin, 5-FU, Cetuximab, and Taxane
  • Official Title: Phase II Trial of Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Platin, 5-FU, Cetuximab, and Taxane

Clinical Trial IDs

  • ORG STUDY ID: 201503060
  • NCT ID: NCT02369458

Conditions

  • Squamous Cell Carcinoma of the Head and Neck
  • Squamous Cell Carcinoma, Head and Neck

Interventions

DrugSynonymsArms
Mitomycin-CMitosol, MitomycinArm 1: p16+ OPSCC
PegfilgrastimNeulasta®, GCSFArm 1: p16+ OPSCC

Purpose

No agent is known to have efficacy in patients with incurable HNSCC that progressed with prior platin, 5-FU, cetuximab and taxane. Herein lies the unmet need to be addressed by this trial. Based on the preclinical and clinical data presented, the investigators propose that mitomycin C will have anti-tumor activity in these patients.

Trial Arms

NameTypeDescriptionInterventions
Arm 1: p16+ OPSCCExperimentalMitomycin C given on Day 1 every 5 weeks (each cycle is 5 weeks). Pegfilgrastim will be given on Day 2 of each cycle (subcutaneous injection)
  • Mitomycin-C
  • Pegfilgrastim
Arm 2: p16- HNSCCExperimentalMitomycin C given on Day 1 every 5 weeks (each cycle is 5 weeks). Pegfilgrastim will be given on Day 2 of each cycle (subcutaneous injection)
  • Mitomycin-C
  • Pegfilgrastim

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed incurable HNSCC of the oral cavity,
             oropharynx, larynx, hypopharynx, and/or Level 1-3 neck node with non-cutaneous SCC and
             unknown primary. "Incurable" is defined as metastatic disease or a local or regional
             recurrence in a previously irradiated site that is unresectable (or patient declines
             resection).

          -  Progression following platin, 5-FU, cetuximab and taxane given for incurable disease.

          -  Measurable disease defined as lesions that can be accurately measured in at least one
             dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
             chest x-ray, or ≥ 10 mm with calipers by clinical exam per RECIST 1.1.

          -  Tissue available (either initial diagnostic or recurrent tissue specimen) for p16
             testing.

          -  At least 18 years of age.

          -  ECOG performance status ≤ 3

          -  Adequate hematologic, renal, and hepatic function as defined below:

               -  Absolute neutrophil count ≥ 1,000/mcl

               -  Platelets ≥ 75,000/mcl

               -  Total bilirubin ≤ 1.5 mg/dL

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN, unless bone
                  metastasis is present in the absence of liver metastasis

               -  Creatinine below ULN (males 0.7-1.30 mg/dl; females 0.6-1.10 mg/dl) OR Creatinine
                  clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above
                  institutional normal

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry, for
             the duration of study participation, and for 1 month after completing treatment.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she must inform her treating physician immediately.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  Other active malignancy with the exception of basal cell or squamous cell carcinoma of
             the skin which were treated with local resection only, carcinoma in situ of the
             cervix, or synchronous H&N primaries.

          -  Currently receiving any other investigational agents.

          -  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 and/or breastfeeding. Patient must have a negative pregnancy test within 7
             days of start of study treatment.

          -  Known active central nervous system (CNS) metastases. Subjects with previously treated
             brain metastases may participate provided they are stable (without evidence of
             progression by imaging for at least four weeks prior to the first dose of trial
             treatment and any neurologic symptoms have returned to baseline), have no evidence of
             new or enlarging brain metastases, and are not using steroids for at least 28 days
             prior to treatment.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to mitomycin C or other agents used in the study.

          -  Known HIV-positivity on combination antiretroviral therapy because of the potential
             for pharmacokinetic interactions with the study drugs. In addition, these patients are
             at increased risk of lethal infections when treated with marrow-suppressive therapy.
             Appropriate studies will be undertaken in patients receiving combination
             antiretroviral therapy when indicated.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor response rate (TRR)
Time Frame:Approximately 6 months (due to estimated median PFS of 6 months)
Safety Issue:
Description:TRR will be evaluated separately in p16- (HPV-unrelated) HNSCC patients and in p16+ (HPV positive) OPSCC patients using two optimal two-stage Simon designs. In both cases, the expected TRR is 10%. A TRR of 30% is considered a clinically significant increase. RECIST 1.1 will be used for this outcome.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Approximately 6 months (due to estimated median PFS of 5.6 months)
Safety Issue:
Description:PFS is defined as the duration of time from start of treatment to time of first radiologic confirmation of progression or death, whichever occurs first. Progressive disease per RECIST 1.1 Target lesions - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Non-target lesions:Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measure:Grades 3 and 4 adverse events
Time Frame:30 days after completion of treatment (estimated treatment completion of 6 months)
Safety Issue:
Description:Using CTCAE Version 3.0
Measure:Overall survival (OS)
Time Frame:Approximately 11 months (due to estimated OS of 10.1 months)
Safety Issue:
Description:
Measure:Quality of life
Time Frame:Baseline, every 5 weeks, and end of treatment (estimated at 6 months)
Safety Issue:
Description:Assessment tools include: EORTC QLQ-C30: this has a total score, one general QOL, and one "within the last week" subscale, as well as a general health item and a single overall QOL item. This study does not use current empirical guidelines for the EORTC-QLQ-30 global score with the understanding that both the magnitude and variance of scores vary considerably from patient to patient, from one time point to another and by such factors as disease condition, age, and comorbidity. The participants can choose from 1-4 with 1 being Not At All and 4 being Very Much. Cognitive Failures Questions (CFQ) - has 3 subscales describing perception, memory, and motor function. A change in 1 standard deviation will be considered a perceptible difference. The participants can choose a scale from 0-4 with 0 being Never and 4 being Very Often.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

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