Squamous Cell Carcinoma of the Penis, Usual Type
Conditions
Keywords
Penis cancer, Chemotherapy, Chemoradiotherapy, Surgery, Phase III
Brief summary
This is an international phase III trial, with a Bayesian design, incorporating two sequential randomisations. It efficiently examines a series of questions that routinely arise in the sequencing of treatment. The study design has evolved from lengthy international consultation that has enabled us to build consensus over which questions arise from current knowledge and practice. It will enable potential randomisation for the majority of patients with inguinal lymph node metastases and will provide data to inform future clinical decisions. InPACT-neoadjuvant patients are stratified by disease burden as assessed by radiological criteria. Treatment options are then defined according to the disease burden strata. Treatment is allocated by randomisation. Patients may be allocated to one of three initial treatments: A. standard surgery (ILND); B. neoadjuvant chemotherapy followed by standard surgery (ILND); or C. neoadjuvant chemoradiotherapy followed by standard surgery (ILND). After ILND, patients are defined as being at low or high risk of recurrence based on histological interpretation of the ILND specimen. Patients at high risk of relapse are eligible for InPACT-pelvis, where they are randomised to either: P. prophylactic PLND Q. no prophylactic PLND
Interventions
PROCEDUREILND - Inguinal Lymph Node Dissection
Surgery to remove the lymph nodes in the groin near to where the cancer first appeared.
DRUGPaclitaxel
Dose 175mg/m2 as part of TIP regimen.
DRUGIfosfamide
Dose 900mg/m2 as part of TIP regimen.
DRUGCisplatin
Dose 15mg/m2 as part of TIP regimen (neoadjuvant chemotherapy arm) Dose 40mg/m2 for use concurrently with raditotherapy (chemoradiotherapy arm)
RADIATIONIntensity modulated radiation treatment (IMRT)
Treatment with very high energy X-rays (radiotherapy).
PROCEDUREProphylactic PLND - pelvic lymph node dissection
Surgery to remove the lymph nodes deeper in the pelvis, further away from where the cancer first appeared, that are at high risk of harbouring cancer.
Sponsors
Institute of Cancer Research, United Kingdom
National Cancer Institute (NCI)
ECOG-ACRIN Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent 2. Measurable disease as determined by RECIST (version 1.1) criteria; 3. Histologically-proven squamous cell carcinoma of the penis, 4. Stage: * any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or; * any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0 or; * any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy), M0 5. Performance Status ECOG 0, 1 or 2.
Exclusion criteria
1. Pure verrucous carcinoma of the penis, 2. Nonsquamous malignancy of the penis, 3. Squamous carcinoma of the urethra, 4. Stage M1, 5. Previous chemotherapy or chemoradiotherapy, 6. Concurrent malignancy (other than SCC or Basal Cell Carcinoma of non-penile skin) that has required surgical or non-surgical treatment in the last 3 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | up to 5 years | The primary outcome measure that will be measured for all trial patients is survival time. This is defined in whole days as the time from the date of randomisation to the date of death from any cause; for those who have not been reported as dead at the time of analysis, the survival time will be censored at the date of last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease specific survival time | up to 5 years | Disease-specific survival time which is defined in whole days as the time from the date of randomisation to the date of death specifically from disease; for those who have not been reported as dead at the time of analysis, the survival time will be censored at the date of last follow-up and for those whose death is reported as non-disease specific then the survival time will be censored at date of death. |
| Number of patients experience a grade 3 or 4 toxicity | up to 5 years | — |
| Disease-free survival time | up to 5 years | Disease-free survival time (DFST) which is defined in whole days as the time from date of randomisation to the date of either locoregional recurrence, distant metastasis or death from disease, whichever occurs first; for those who have not been reported as experiencing any of these events, the DFST will be censored at the date last known to be alive and free of disease or date of non-disease-specific death. A supplementary exploratory outcome measure will also be calculated taking date of penectomy as the origin rather than date of randomisation. Subsidiary outcome measures will be * locoregional recurrence free survival time (LRFST). * distant metastases free survival time (DMFST). * A supplementary exploratory outcome measure will also be calculated taking date of penectomy as the origin for all these outcome measures rather than date of randomisation. |
| Occurrence of surgical complication | up to 5 years | — |
| Is it possible to achieve pathological nodal assessment after chemotherapy | 12 weeks | Feasibility of pathological nodal assessment after chemotherapy which is recorded as whether or not it was possible to achieve a pathological nodal assessment after chemotherapy. |
| Quality of life | Baseline, 3, 6, 9, 12, 18, 24 and 36 months | Measured using the EORTC-QLQC30 and Lymphodema-QL |
| Occurrence of Pathological complete remission | Time to complete remission after randomisation | Measured for all patients in InPACT-neoadjuvant: Absolute absence of disease on histological examination |
| Operability | 2-6 weeks | Measured for all trial patients in InPACT-neoadjuvant. Operability which will be recorded as whether or not the planned inguinal node dissection was undertaken and the reasons if it did not occur. |
| Occurrence of Lower limb/scrotal oedema | up to 5 years | Occurrence of Lower limb/scrotal oedema which is recorded as whether or not the patient experiences a lower limb or scrotal oedema |
| On-schedule delivery of neoadjuvant therapy | After randomisation up to 12 weeks | Feasibility of on-schedule delivery of neoadjuvant therapy |
Countries
United Kingdom, United States
Contacts
STUDY_CHAIRSteve Nicholson
Mid and South Essex NHS Foundation Trust
STUDY_CHAIRCurtis Pettaway
University of Texas M.D. Anderson Cancer Center ; 713-792-3250 ; cpettawa@mdanderson.org
Outcome results
None listed