Clinical trial NCT03114254: A Trial of Cabazitaxel Chemotherapy in Relapsed Locally Advanced &/or Metastatic Carcinoma of the Penis
Official title: A Phase II Trial of Cabazitaxel Chemotherapy in Relapsed Locally Advanced &/or Metastatic Carcinoma of the Penis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Penile Neoplasm
Keywords: Recurrent
Locally advanced
Metastatic
Lead sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2017-04-14
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An evaluation of the activity of cabazitaxel chemotherapy in relapsed cancer of the penis. Safety and tolerability will be monitored and survival will be assessed. It is hypothesised that cabazitaxel is useful in increasing progression free survival in relapsed penile cancer.

Detailed description: First line treatment of penile cancer often combines Docetaxel, Cisplatin and 5Fluouracil (5FU) and there is currently no United Kingdom standard second line agent. Carbazitaxel has been shown to kill both taxane resistant and sensitive cells. JAVA-P is a phase two, single arm study of the use of carbazitaxel for relapsed, locally advanced or metastatic carcinoma of the penis. Seventeen patients will be recruited over two years, with adverse events and progression free survival being assessed. Results may indicate the need for larger studies to evaluate carbazitaxel as a first line agent.

Eligibility criteria: Inclusion Criteria:

* Histologically-proven squamous cell carcinoma of the penis
* Performance status ECOG 0-2
* Written informed consent
* Measurable disease as per RECIST 1.1
* Fit to receive cabazitaxel as second line chemotherapy
* Previously received TPF or cisplatin-5FU as first line systemic chemotherapy for penile cancer
* Adequate organ function as evidenced by the following peripheral blood counts and serum biochemistry at enrollment:

  * Neutrophils ≥1.5 x 109/L
  * Haemoglobin ≥10 g/dL
  * Platelets ≥100 x 109/L
  * Total bilirubin \<1.5 upper limit of normal (ULN)
  * Alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤1.5 x ULN
  * Serum creatinine ≤1.5 x ULN. (If creatinine is 1.0-1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with a creatinine clearance \<60 ml/min should be excluded.)

Exclusion Criteria:

* Pure veruccous carcinoma of the penis
* Squamous carcinoma of the urethra
* T1 N1 M0 disease
* T2 N1 M0 disease
* Unfit for this regimen (as assessed by the multidisciplinary team)
* Contraindication to chemotherapy
* ECOG Performance Status \> 2
* Active Grade ≥2 peripheral neuropathy
* Active secondary cancers
* Other concurrent serious illness or medical conditions
* Electrocardiogram (ECG) evidence of uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension, history of congestive heart failure, or myocardial infarction within last 6 months.
* Uncontrolled diabetes mellitus.
* History of severe hypersensitivity reaction (≥grade 3) to docetaxel
* History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
* Active infection requiring systemic antibiotic or anti-fungal medication
* Participation in another clinical trial with any investigational drug within 30 days prior to study registration.
* Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments.
* Concurrent or planned treatment with strong inducers of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments.

Primary outcomes:
measure: Complete response
timeFrame: 18 weeks
measure: Partial response
timeFrame: 18 weeks
Secondary outcomes:
measure: Progression free survival
timeFrame: Until patient progresses, which is approximately 6 weeks after randomisation
measure: Overall survival
timeFrame: Until patient dies, which is approximately 3 months after randomisation
measure: Acute toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse Reactions and by grades and the worst grade).
timeFrame: After each cycle (every 3 weeks) for maximally 6 cycles therefore 18 weeks whilst on treatment and at the 3 month visit timepoint
measure: Late toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse Reactions and by grades and the worst grade).
timeFrame: From 3 months post treatment Cycle 1 Day 1 to up to 6 months recorded at the 3 month and 6 month timepoint.
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre, Horfield Road
city: London
country: United Kingdom
facility: Universitty College Hospitals NHS Trust
Study officials:
affiliation: University Hospitals Bristol and Weston NHS Foundation Trust
name: Amit Bahl
role: PRINCIPAL_INVESTIGATOR
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