Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma, Head and Neck
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Mitomycin-C
Pegfilgrastim
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck
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 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.
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A: p16+ OPSCC
Cohort 2: p16- HNSCC
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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 1.1
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.
Number of Participants With Grade 3/4/5 Adverse Events
-Using CTCAE Version 3.0
Overall Survival (OS)
Full Information
NCT ID
NCT02369458
First Posted
February 16, 2015
Last Updated
August 10, 2023
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT02369458
Brief Title
Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies
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 Standard Therapies
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 14, 2015 (Actual)
Primary Completion Date
June 1, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma, Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: p16+ OPSCC
Arm Type
Experimental
Arm Description
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)
Arm Title
Cohort 2: p16- HNSCC
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Mitomycin-C
Other Intervention Name(s)
Mitosol, Mitomycin
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
•Neulasta®, GCSF
Primary Outcome Measure Information:
Title
Tumor Response Rate (TRR)
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.
Time Frame
Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Title
Tumor Response Rate (TRR) for Participants Enrolled Post October 2020
Description
TRR will be evaluated in p16+ (HPV positive) OPSCC HNSCC patients
RECIST 1.1 will be used for this outcome.
Time Frame
Approximately 6 months (median 4.0 months with full range of 0.5-12.0 months)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
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.
Time Frame
Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Title
Number of Participants With Grade 3/4/5 Adverse Events
Description
-Using CTCAE Version 3.0
Time Frame
28 days after completion of treatment (median length of follow-up was 98 days, full range of 31-463 days)
Title
Overall Survival (OS)
Time Frame
Approximately 11 months (due to estimated OS of 10.1 months)
Other Pre-specified Outcome Measures:
Title
Quality of Life as Measured by the EORTC QLQ-C30
Description
-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.
Time Frame
Baseline, every 5 weeks, and end of treatment (estimated at 6 months)
Title
Quality of Life as Measured by the Cognitive Failures Questions (CFQ)
Description
-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.
Time Frame
Baseline, every 5 weeks, and end of treatment (estimated at 6 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Oppelt, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies
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