Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma, Head and Neck
Conditions
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.
Interventions
DRUGMitomycin-C
DRUGPegfilgrastim
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate (TRR) | Approximately 6 months (median 5.6 months with full range of 0.1-33.7 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. |
| Tumor Response Rate (TRR) for Participants Enrolled Post October 2020 | Approximately 6 months (median 4.0 months with full range of 0.5-12.0 months) | * TRR will be evaluated in p16+ (HPV positive) OPSCC HNSCC patients * RECIST 1.1 will be used for this outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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) | -Defined as the date of first treatment to the date of death, last date alive, or date of patient withdrawal. |
| Number of Participants With Grade 3/4/5 Adverse Events | 28 days after completion of treatment (median length of follow-up was 96 days, full range of 3-463 days) | -Using CTCAE Version 3.0 |
| Progression-free Survival (PFS) | Approximately 6 months (median 5.6 months with full range of 0.1-33.7 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life as Measured by the EORTC QLQ-C30 | Baseline, every 5 weeks, and end of treatment (estimated at 6 months) | -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. |
| Quality of Life as Measured by the Cognitive Failures Questions (CFQ) | Baseline, every 5 weeks, and end of treatment (estimated at 6 months) | -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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 35 |
| Cohort B: 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) | 13 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Determined to be not eligible | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort A: p16+ OPSCC | Total | Cohort B: p16- HNSCC |
|---|---|---|---|
| Age, Continuous | 61 years | 61 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 48 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 43 Participants | 8 Participants |
| Region of Enrollment United States | 35 participants | 48 participants | 13 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 34 Participants | 42 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 47 / 47 |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 21 / 47 |
Outcome results
Primary
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.
Time frame: Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Population: One participant in each arm were not evaluable for tumor response rate.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: p16+ OPSCC | Tumor Response Rate (TRR) | 3 Participants |
| Cohort B: p16- HNSCC | Tumor Response Rate (TRR) | 0 Participants |
Primary
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.
Time frame: Approximately 6 months (median 4.0 months with full range of 0.5-12.0 months)
Population: Only participants enrolled post October 2020 are evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: p16+ OPSCC | Tumor Response Rate (TRR) for Participants Enrolled Post October 2020 | 0 Participants |
Secondary
Number of Participants With Grade 3/4/5 Adverse Events
-Using CTCAE Version 3.0
Time frame: 28 days after completion of treatment (median length of follow-up was 96 days, full range of 3-463 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: p16+ OPSCC | Number of Participants With Grade 3/4/5 Adverse Events | 26 Participants |
Secondary
Overall Survival (OS)
-Defined as the date of first treatment to the date of death, last date alive, or date of patient withdrawal.
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: p16+ OPSCC | Overall Survival (OS) | 6.6 months |
| Cohort B: p16- HNSCC | Overall Survival (OS) | 3.2 months |
Secondary
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.
Time frame: Approximately 6 months (median 5.6 months with full range of 0.1-33.7 months)
Population: One participant in each arm were not evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: p16+ OPSCC | Progression-free Survival (PFS) | 2.2 months |
| Cohort B: p16- HNSCC | Progression-free Survival (PFS) | 2.1 months |
Other Pre-specified
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.
Time frame: Baseline, every 5 weeks, and end of treatment (estimated at 6 months)
Other Pre-specified
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.
Time frame: Baseline, every 5 weeks, and end of treatment (estimated at 6 months)