Study with pazopanib and weekly paclitaxel in penile carcinoma

Conditions: Metastatic or locally advanced squamous penile carcinoma
MedDRA version: 17.1Level: LLTClassification code 10034318Term: Penile squamous cell carcinoma stage IVSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003127-22-ES

Lead Sponsor: SOGUG (Spanish Oncology Genitourinary Group)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: Not specified

Inclusion Criteria

1. Written informed consent
2. Age >= 18 years
3. Histologically confirmed diagnosis of squamous cell carcinoma of the penis
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Measurable disease criteria according to RECIST criteria (version 1.1)
6. Progressive disease after treatment with cisplatin or carboplatin based chemotherapy. At least two cycles of chemotherapy had been administered either in neoadyuvant, adyuvant or metastatic setting.
7. Archived tumor tissue must be provided for all subjects for biomarker analysis before and/or during treatment with investigational product.
8. Adequate organ system function
- Haemoglobin >= 9.0 gr/dl (5.6 mmol/L) and stable in the previous 4 weeks to start study treatment
- Neutrophils >= 1.5 x 10*9/L
- Platelets >= 100 x 10*9/L
- Total bilirubin <= 1.5 x UNL
- AST/SGOT and ALT/SGPT <= 2.5 x UNL
9. Normal coagulation tests:
- Prothrombin time (PT) or international normalized ratio (INR) <= 1.2 X ULN
- Activated partial thromboplastin time (aPTT) <= 1.2 X ULN
10. Are able to swallow and retain oral tablets
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

1. Prior malignancy.
2. Central nervous system metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants
3. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
4. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.
5. Corrected QT interval (QTc) > 480 msecs
6. History of any one or more of the following cardiovascular conditions within the past 6 months:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Coronary artery bypass graft surgery
- Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
8. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
9. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
10. Evidence of active bleeding or bleeding diathesis.
11. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
12. Recent hemoptysis (>= 1/2 teaspoon [2.5 mL]) of red blood within 8 weeks before first dose of study drug).
13. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subjects safety, provision of informed consent, or compliance to study procedures.
14. Unable or unwilling to discontinue use of prohibited medications 14 days prior to the first dose of study drug and for the duration of the study.
15. Treatment with any of the following anti-cancer therapies:
- radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
- chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days prior to the first dose of Pazopanib
16. Administration of any non-oncologic investigational drug within 30 days prior to receiving the first dose of study treatment
17. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
18. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or paclitaxel and/or excipients that contraindicates their participation.
19. Previous taxane or/and antiVEGF treatment would not allow patient to participate in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Every 8 weeks;Main Objective: Evaluate response rate in terms of complete and partial response (RECIST criteria version 1.1);Secondary Objective: - Clinical benefit rate (complete and partial response and stable disease) evaluated according RECIST criteria version 1.1<br>- Progression free survival<br>- Response duration<br>- Overall survival <br>- Safety and tolerability profile;Primary end point(s): Response rate in terms of complete and partial response (RECIST criteria version 1.1)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Clinical benefit rate (complete and partial response and stable disease) evaluated according RECIST criteria version 1.1<br>- Progression free survival<br>- Response duration<br>- Overall survival <br>- Safety and tolerability profile;Timepoint(s) of evaluation of this end point: - Every 8 weeks<br>- Every 8 weeks<br>- Every 8 weeks<br>- Every 8 weeks<br>- Every 4 weeks