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

• ClinicalTrials.gov Identifier: NCT02369458
• Recruitment Status: Recruiting
• First Posted: February 24, 2015
• Last Update Posted: October 20, 2020
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck	Drug: Mitomycin-C; Drug: Pegfilgrastim	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 14, 2015
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: 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: Mitomycin-C; Other Names: Mitosol; Mitomycin; Drug: Pegfilgrastim; Other Names: •Neulasta®; GCSF
Experimental: Arm 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: Mitomycin-C; Other Names: Mitosol; Mitomycin; Drug: Pegfilgrastim; Other Names: •Neulasta®; GCSF

Outcome Measures

Primary Outcome Measures :

1. Tumor response rate (TRR) [ Time Frame: Approximately 6 months (due to estimated median PFS of 6 months) ]

   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 :

1. Progression-free survival (PFS) [ Time Frame: Approximately 6 months (due to estimated median PFS of 5.6 months) ]

   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.
2. Grades 3 and 4 adverse events [ Time Frame: 28 days after completion of treatment (estimated treatment completion of 6 months) ]
   Using CTCAE Version 3.0
3. Overall survival (OS) [ Time Frame: Approximately 11 months (due to estimated OS of 10.1 months) ]
4. Quality of life [ Time Frame: Baseline, every 5 weeks, and end of treatment (estimated at 6 months) ]

   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.

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Peter Oppelt, M.D.; 636-916-9922; poppelt@wustl.edu

Locations

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Peter Oppelt, M.D. 636-916-9922 poppelt@wustl.edu

Principal Investigator: Peter Oppelt, M.D.

Sub-Investigator: Kevin Palka, M.D.

Sub-Investigator: Douglas Adkins, M.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

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

More Information

Additional Information:

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

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02369458
• Other Study ID Numbers: 201503060
• First Posted: February 24, 2015
• Last Update Posted: October 20, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Mitomycins; Mitomycin; Antibiotics, Antineoplastic; Antineoplastic Agents; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors