Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies

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 Standard Therapies

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck
• Intervention / Treatment: Drug: Pegfilgrastim; Drug: Mitomycin-C

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 and immunotherapy 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: p16+ OPSCC; Mitomycin 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)	Drug: Pegfilgrastim; Other Names: GCSF; •Neulasta®; Drug: Mitomycin-C; Other Names: Mitomycin; Mitosol
Experimental: Cohort 2: p16- HNSCC; Mitomycin 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)	Drug: Pegfilgrastim; Other Names: GCSF; •Neulasta®; Drug: Mitomycin-C; Other Names: Mitomycin; Mitosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response Rate (TRR)	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.	Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Tumor Response Rate (TRR) for Participants Enrolled Post October 2020	TRR will be evaluated in p16+ (HPV positive) OPSCC HNSCC patients; RECIST 1.1 will be used for this outcome.	Approximately 6 months (median 4.0 months with full range of 0.5-12.0 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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 1.1Target 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.	Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Number of Participants With Grade 3/4/5 Adverse Events	-Using CTCAE Version 3.0	28 days after completion of treatment (median length of follow-up was 96 days, full range of 3-463 days)
Overall Survival (OS)	-Defined as the date of first treatment to the date of death, last date alive, or date of patient withdrawal.	Through completion of follow-up (median length of follow-up Cohort A= 6.6 months IQR 2.7-12.0 months, median length of follow-up Cohort B=3.2 months IQR 1.5-9.4 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life as Measured by the EORTC QLQ-C30	-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.	Baseline, every 5 weeks, and end of treatment (estimated at 6 months)
Quality of Life as Measured by the Cognitive Failures Questions (CFQ)	-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.	Baseline, every 5 weeks, and end of treatment (estimated at 6 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Peter Oppelt, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2015
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): November 1, 2024

Study Registration Dates

• First Submitted: February 16, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimated): February 24, 2015

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Quinones; Azirines; Mitomycins; Indolequinones; Mitomycin; pegfilgrastim
• Other Study ID Numbers: 201503060

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No