Capecitabine or 5-FU With Pegylated Interferon Alpha-2b in Unresectable/Metastatic Cutaneous Squamous Cell Carcinoma

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02218164
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 99.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of Skin; Carcinoma, Squamous Cell	Drug: Pegylated Interferon alpha-2b; Drug: Capecitabine; Drug: 5-FU	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Capecitabine or 5-FU With Pegylated Interferon Alpha-2b in Unresectable/Metastatic Cutaneous Squamous Cell Carcinoma
• Actual Study Start Date: Aug 12, 2014
• Actual Primary Completion Date: Jul 19, 2017
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Capecitabine or 5-FU with Pegylated Interferon alpha-2b Participants will start the Capecitabine pills on day 1 thru day 14 and be off for 7 days (day 15-day 21). Participants will receive 5-FU days 1-4 of each 21 day cycle. Participants will receive the Interferon alpha-2b injection weekly every week. The three week period is referred to as one cycle. After three cycles, new imaging studies will be performed that will 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).

Drug: Pegylated Interferon alpha-2b; 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.; Other Names: PEG Interferon Alpha-2b PEG-INTRON PEGASYS ; Drug: Capecitabine; 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.; Other Names: Xeloda ; Drug: 5-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.; Other Names: 5-fluorouracil

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. Occurence of Treatment Related Serious Adverse Events (SAEs) [1 year]

   Number of participants with treatment emergent SAEs, overall and per Event Description.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Christine Chung, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 15, 2017

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT02218164
• Other Study ID Numbers: MCC-17759
• First Posted: Aug 15, 2014
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: metastatic; cutaneous; skin cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Fluorouracil; Capecitabine

Study Results

Participant Flow

Recruitment Details	Participants were recruited at Moffitt Cancer Center from August 2014 through May 2017.

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Overall Participants	8
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	72
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race/Ethnicity, Customized (Count of Participants)
White Non-Hispanic	8 100%
Black or African American	0 0%
Asian	0 0%
Hispanic or Latino	0 0%
Other	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Measure Participants	8
Stable Disease	4 50%
Complete Response	1 12.5%
Partial Response	1 12.5%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Measure Participants	8
Median (95% Confidence Interval) [months]	11.3

3. Secondary Outcome

Title	Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received study treatment.

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Measure Participants	8
Expired in less than a year	4 50%
Alive at the end of the year	2 25%
Had not completed survival follow-up at closeout	2 25%

4. Secondary Outcome

Title	Occurence of Treatment Related Serious Adverse Events (SAEs)
Description	Number of participants with treatment emergent SAEs, overall and per Event Description.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
Measure Participants	8
Any Related SAE	1 12.5%
Dehydration	1 12.5%
INR Increased	1 12.5%

Adverse Events

Time Frame	3 years
Arm/Group Title	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
Arm/Group Description	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).
All Cause Mortality
	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Serious Adverse Events
	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)
Gastrointestinal disorders
Dysphagia	1/8 (12.5%)	1
General disorders
General disorders and administration site conditions - Other, Medication error	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Fall	1/8 (12.5%)	1
Investigations
INR increased	1/8 (12.5%)	1
Metabolism and nutrition disorders
Dehydration	2/8 (25%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms - Other, Death due to disease progression	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	2/8 (25%)	2
Vascular disorders
Thromboembolic event	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Capecitabine or 5-FU With Pegylated Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anemia	2/8 (25%)	2
Cardiac disorders
Cardiac disorders - Other, Atrial fibrillation with rapid ventricular response	1/8 (12.5%)	1
Ear and labyrinth disorders
Ear pain	1/8 (12.5%)	1
Eye disorders
Eye disorders - Other, Right eye edema	1/8 (12.5%)	1
Gastrointestinal disorders
Diarrhea	2/8 (25%)	2
Dysphagia	1/8 (12.5%)	1
Constipation	1/8 (12.5%)	1
Gastrointestinal disorders - Other, Stomatitis	1/8 (12.5%)	1
Nausea	1/8 (12.5%)	1
Stomach pain	1/8 (12.5%)	1
Vomiting	1/8 (12.5%)	1
General disorders
General disorders and administration site conditions - Other, Failure to thrive	2/8 (25%)	3
Injection site reaction	3/8 (37.5%)	4
Chills	2/8 (25%)	2
Fatigue	2/8 (25%)	4
Fever	2/8 (25%)	2
Edema face	1/8 (12.5%)	1
Pain	1/8 (12.5%)	1
Infections and infestations
Infections and infestations - Other, Staph	2/8 (25%)	2
Skin infection	1/8 (12.5%)	1
Urinary tract infection	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Fall	2/8 (25%)	2
Dermatitis radiation	1/8 (12.5%)	2
Radiation recall reaction (dermatologic)	1/8 (12.5%)	1
Investigations
White blood cell decreased	4/8 (50%)	6
Weight loss	3/8 (37.5%)	6
INR increased	1/8 (12.5%)	1
Neutrophil count decreased	1/8 (12.5%)	1
Platelet count decreased	1/8 (12.5%)	1
Metabolism and nutrition disorders
Anorexia	5/8 (62.5%)	5
Dehydration	2/8 (25%)	3
Hypokalemia	1/8 (12.5%)	1
Hyponatremia	1/8 (12.5%)	1
Hypophosphatemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Myalgia	2/8 (25%)	3
Back pain	1/8 (12.5%)	1
Bone pain	1/8 (12.5%)	1
Joint range of motion decreased	1/8 (12.5%)	1
Trismus	1/8 (12.5%)	1
Nervous system disorders
Peripheral sensory neuropathy	2/8 (25%)	2
Dysgeusia	1/8 (12.5%)	1
Headache	1/8 (12.5%)	1
Seizure	1/8 (12.5%)	1
Tremor	1/8 (12.5%)	1
Psychiatric disorders
Confusion	1/8 (12.5%)	1
Depression	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/8 (37.5%)	3
Hoarseness	1/8 (12.5%)	1
Nasal congestion	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Pruritus	3/8 (37.5%)	4
Palmar-plantar erythrodysesthesia syndrome	2/8 (25%)	2
Skin and subcutaneous tissue disorders - Other, Arm wound (non-lesion)	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders - Other, New Skin cancer - different histology	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders - Other, Finger cracking	1/8 (12.5%)	1
Dry skin	1/8 (12.5%)	1
Nail ridging	1/8 (12.5%)	1
Vascular disorders
Hypotension	3/8 (37.5%)	4
Hematoma	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.