Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02541903
• Collaborator: (none)
• Enrollment: 8
• Locations: 3
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Penile squamous cell carcinoma (PSCC) is a highly aggressive and relatively rare disease. Supportive evidence for the value of systemic therapy does not exist for this disease and there are no agents currently approved by regulatory agencies. This study will evaluate the drug Gilotrif in patients with metastatic progressive PSCC following chemotherapy. Gilotrif has shown supportive evidence in non-small cell lung cancer by inhibiting certain proteins that are also found in PSCC. The drug has the potential for some patients to exhibit a response contributing to a greater quality of life.

Condition or Disease	Intervention/Treatment	Phase
Penile Squamous Cell Carcinoma (PSCC)	Drug: Gilotrif	Phase 2

Detailed Description

This is a non-randomized trial phase 2 trial in which the drug Gilotrif will be administered at an oral dosage of 40 mg daily. This will continue until there is disease progression or severe toxicities. Patients will undergo a clinical exam every 4 weeks as well as have blood collected. Radiographic scans will be done every 8 weeks.

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 Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma Following Systemic Therapy
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Jan 26, 2019
• Actual Study Completion Date: Apr 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gilotrif Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks).	Drug: Gilotrif; Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Progression Free Survival at 6 Months [6 months following study treatment]

   Death will signify the time of progression free survival. Otherwise, the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 will be used to evaluate disease progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Response Rate [Baseline up to 3 months]

   The Response Evaluation Criteria in Solid Tumors guidelines version 1.1 and disease assessment scans (bone, CT) will be used to evaluate tumor response.

2. Overall Survival [Baseline to death (assessed up to 30 months).]

   From date of study enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 30 months.

3. Toxicities [Baseline up to 18 months]

   The number of adverse events and serious adverse events will be tabulated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically or cytologically confirmed PSCC.

2. Patients with metastatic or locally advanced unresectable PSCC.

3. Progressive disease after ≥1 prior chemotherapy regimens.

4. Measurable disease by RECIST 1.1 criteria.

5. Prior regimen within 6 months

6. ECOG performance status 0-2.

7. Adequate organ function, defined as all of the following:

• Absolute neutrophil count (ANC) >1500 /mm3. Platelet count >100,000/ mm3.

• Estimated creatinine clearance ≥ 45ml/min.

• Total Bilirubin <1.5 times upper limit of institutional normal; Aspartate amino transferase (AST) or alanine amino transferase (ALT) <2.5 times the upper limit of institutional normal (ULN).

• Hemoglobin ≥8.5 g/dl.

1. Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to NCI CTCAE version 4.03 grade <1, in the opinion of the Treating Physician.

2. Ability to understand and willingness to sign a written informed consent. Age ≥18 years or age of majority at the participating site, whichever is greater.

3. Availability of 20 archival formalin-fixed paraffin embedded tumor tissue slides.

Exclusion Criteria:

1. Patients will have recovered from toxicities from prior systemic anticancer treatment or local therapies.

2. Prior EGFR inhibitors.

3. Major surgery within 4 weeks or minor surgery within 2 weeks before registration or scheduled for surgery during the projected course of the study. Wounds will be completely healed prior to study entry and patients recovered from all toxicities from surgery. Placement of vascular access device is not considered major or minor surgery in this regard.

4. Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least 3 weeks prior to enrollment. If the irradiated area is the only site of disease, there will be progressive disease.

5. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to registration.

6. Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.

7. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.

8. Requiring treatment with any of the prohibited concomitant medications listed in the protocol that cannot be stopped for the duration of trial participation.

9. Known pre-existing interstitial lung disease.

10. Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption).

11. Active hepatitis B infection (defined as presence of Hep BsAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.

12. Meningeal carcinomatosis.

13. Patients with active brain or subdural metastases are not eligible, unless they have completed local (radiation) therapy and have discontinued the use of corticosteroids or have been on stable dose of corticosteroids for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases will be stable for at least 4 weeks before starting study treatment.

14. Any active or uncontrolled infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Southern California	Los Angeles	California	United States	90033
3	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

• Principal Investigator: Lisle Nabell, MD, University of Alabama at Birmingham
• Study Chair: Tanya Dorff, MD, University of Southern California

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Apr 3, 2019

More Information

Publications

None provided.

• Responsible Party: Lisle Nabell, Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02541903
• Other Study ID Numbers: F150330009 (UAB 14113)
• First Posted: Sep 4, 2015
• Last Update Posted: Apr 14, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Lisle Nabell, Professor, University of Alabama at Birmingham: Epidermal growth factor receptor (EGFR),; Human Papillomavirus (HPV); Penile squamous cell carcinoma (PSCC); Gilotrif
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Afatinib

Study Results

Participant Flow

Recruitment Details	The study was open to accrual between 10/6/2015 and 2/26/2019. Two sites were involved - the University of Alabama at Birmingham, and the University of Southern California.

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Overall Participants	8
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52.4
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 12.5%
White	6 75%
More than one race	0 0%
Unknown or Not Reported	1 12.5%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Progression Free Survival at 6 Months
Description	Death will signify the time of progression free survival. Otherwise, the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 will be used to evaluate disease progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	6 months following study treatment

Outcome Measure Data

Analysis Population Description

1 participant expired before receiving treatment

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Measure Participants	7
Count of Participants [Participants]	1 12.5%

2. Secondary Outcome

Title	Response Rate
Description	The Response Evaluation Criteria in Solid Tumors guidelines version 1.1 and disease assessment scans (bone, CT) will be used to evaluate tumor response.
Time Frame	Baseline up to 3 months

Outcome Measure Data

Analysis Population Description

The response rate was calculated using those participants that showed regression or shrinkage at restaging scans.

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Measure Participants	8
Count of Participants [Participants]	2 25%

3. Secondary Outcome

Title	Overall Survival
Description	From date of study enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 30 months.
Time Frame	Baseline to death (assessed up to 30 months).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Measure Participants	8
Mean (90% Confidence Interval) [days]	83

4. Secondary Outcome

Title	Toxicities
Description	The number of adverse events and serious adverse events will be tabulated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
Measure Participants	8
Number [Number of toxicities seen in patients]	5

Adverse Events

Time Frame	Adverse were collected every month during the study period and post-treatment (within 30 days)
Arm/Group Title	Gilotrif
Arm/Group Description	Gilotrif will be administered orally at 40 mg dosage once daily. Continuous administration of 4 weeks is considered one cycle. Therapy will continue until progression of the disease or severe toxicities. Labs will be monitored with routine blood collections every cycle and a CT scan will be done every two cycles (8 weeks). Gilotrif: Patients will take a single oral dose of Gilotrif each day starting at 40 mg. Dose escalation and reductions can occur.
All Cause Mortality
	Gilotrif
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Serious Adverse Events
	Gilotrif
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
General disorders
Fatigue	1/8 (12.5%)	1
Death	1/8 (12.5%)	1
Infections and infestations
Hospitalization	1/8 (12.5%)	1
Vascular disorders
Deep Venous Thrombosis	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Gilotrif
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
General disorders
Pain in scrotal region	1/8 (12.5%)	1
Infections and infestations
cellulitis	1/8 (12.5%)	1
Vascular disorders
Decreased platelet count	1/8 (12.5%)	1
Anemia	1/8 (12.5%)	1

Limitations/Caveats

This study was closed early due to poor enrollment.

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.