Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Skin
Conditions
Keywords
metastatic, cutaneous, skin cancer
Brief summary
The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in patients with squamous cell carcinoma of the skin. Specifically, investigators want to determine if the combination of 5-FU/Capecitabine (oral pills) and Interferon alpha-2b (injection) can help people with advanced cases of squamous cell carcinoma of the skin. For participants that are not approved for oral capecitabine, treating physicians will use continuous infusion 5-FU. Both 5-FU/Capecitabine and Interferon alpha-2b have been used separately to treat squamous cell carcinoma of the skin and are FDA approved in other cancer types.
Interventions
Drug administration will occur on an outpatient basis at the infusion center at Moffitt Cancer Center. Dose will be weight-based. Starting treatment doses of 3 mcg/kg will be given subcutaneously (SC) injection in the thigh, abdominal wall, or upper arm every week for a total of 27 weeks as tolerated.
DRUGCapecitabine
Drug administration will be on an outpatient basis. Capecitabine will be administered at an initial dose of 800 mg/m\^2 by mouth twice daily on days 1-14 of a 21 day cycle with days 15-21 off. This cycle will be repeated every 21 days during the study for a maximum of 9 cycles as tolerated. Administration via feeding tube in patients unable to swallow is permitted.
DRUG5-FU
If participants are not able to acquire oral capecitabine, then treating physicians will start participants on infusional 5-FU which can be delivered via standard of care. Participants will need to have a port placed for continuous infusion treatments. 5-FU pumps will be activated in the infusion center at Moffitt Cancer Center with a starting dose of 800 mg/m\^2 days 1-4, with pump removal on day 5 at the infusion center. 5-FU pumps will be attached every 21 days (1 cycle) for a maximum of 9 cycles.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have histologically or cytologically confirmed squamous cell carcinoma of the skin. Potential participants who present with squamous cell carcinoma of unknown primary lesions at the time of diagnosis will be eligible if patients have a plausible primary skin site removed in the past. Similarly, potential participants with neck, parotid, or facial lymph nodes positive for squamous cell carcinoma with no identifiable mucosal primary would also be eligible. * Must have measurable disease, defined by Response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least one lesion that can be accurately measured in at least one dimension of \>10 mm by CT, MRI, or calipers * There is no limitation to prior treatments with local, regional, topical or systemic agents, except for prior systemic treatment with 5-fluorouracil or prodrugs thereof. Prior topical treatment with 5-fluorouracil is permitted. Patients who are on chronic daily doses of prednisone of greater than 10 mg are excluded. There is no restriction on timing of last treatments as long as patients have recovered from all expected toxicities and at least 21 days have passed since last administration. * Life expectancy of greater than 3 months * Eastern Cooperative Oncology Group (ECOG) performance status \<=2 (Karnofsky \>=60% * Must have normal organ and marrow function * Must not be candidates for curative locoregional treatments. Patients with recurrent locoregional disease following surgery and/or radiation for who a resection is unacceptably morbid and unlikely to be curative are eligible. * Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Have had chemotherapy or radiotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier * May not be receiving any other investigational agents * Known brain metastases * History of allergic reactions attributed to compounds of similar chemical or biologic composition to either 5-FU/Capecitabine or Interferon * Uncontrolled, ongoing illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, psychiatric illness/social situations that would limit compliance with study requirements * Women who are pregnant or breastfeeding * Any heart or lung transplant patient on immunosuppressive agents. Renal transplant patients are allowed if patient is willing to reduce immunosuppressive agents and understand risk of rejection and possible need to return to dialysis. Patients with Chronic Lymphocytic Leukemia (CLL) or other hematologic malignancies are allowed as long as they meet other criteria listed above.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 9 weeks per participant | ORR: Stable Disease (SD); Partial Response (PR); Complete Response (CR). Response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of Treatment Related Serious Adverse Events (SAEs) | 1 year | Number of participants with treatment emergent SAEs, overall and per Event Description. |
| Progression Free Survival (PFS) | 1 year | PFS: Alive without RECIST progression. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Overall Survival (OS) | 1 year | OS: The time from registration to death or date of last contact. Participants with overall survival at 1 year. Kaplan-Meier estimator will be utilized. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at Moffitt Cancer Center from August 2014 through May 2017.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b Capecitabine pills on day 1 thru day 14 and be off for 7 days (day 15-day 21). 5-FU days 1-4 of each 21 day cycle. Interferon alpha-2b injection weekly every week. 3 week period is referred to as one cycle.
After 3 cycles, new imaging studies will be performed to measure how the disease is responding to treatment. Participants whose disease is stable or improved will undergo an additional 3 cycles of therapy and the imaging studies will be repeated. Again, participants whose disease is stable or improved will undergo a final 3 cycles of treatment (a total 27 weeks of treatment). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Capecitabine or 5-FU With Pegylated Interferon Alpha-2b |
|---|---|
| Age, Continuous | 72 years |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 8 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 5 / 8 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR: Stable Disease (SD); Partial Response (PR); Complete Response (CR). Response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: 9 weeks per participant
Population: All participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Objective Response Rate (ORR) | Stable Disease | 4 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Objective Response Rate (ORR) | Complete Response | 1 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Objective Response Rate (ORR) | Partial Response | 1 Participants |
Secondary
Occurence of Treatment Related Serious Adverse Events (SAEs)
Number of participants with treatment emergent SAEs, overall and per Event Description.
Time frame: 1 year
Population: All participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Occurence of Treatment Related Serious Adverse Events (SAEs) | Dehydration | 1 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Occurence of Treatment Related Serious Adverse Events (SAEs) | Any Related SAE | 1 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Occurence of Treatment Related Serious Adverse Events (SAEs) | INR Increased | 1 Participants |
Secondary
Overall Survival (OS)
OS: The time from registration to death or date of last contact. Participants with overall survival at 1 year. Kaplan-Meier estimator will be utilized.
Time frame: 1 year
Population: All participants who received study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Overall Survival (OS) | Expired in less than a year | 4 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Overall Survival (OS) | Alive at the end of the year | 2 Participants |
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Overall Survival (OS) | Had not completed survival follow-up at closeout | 2 Participants |
Secondary
Progression Free Survival (PFS)
PFS: Alive without RECIST progression. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 1 year
Population: All participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | Progression Free Survival (PFS) | 11.3 months |