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Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Arm A - Standard Surgery (ILND) 		Part of randomisation 1. The total treatment duration (Inguinal Lymph Node Dissection (ILND)) is estimated to be over 1 day for those patients allocated to Arm A - standard surgery.
  • Procedure: ILND - Inguinal Lymph Node Dissection
    Surgery to remove the lymph nodes in the groin near to where the cancer first appeared.
Experimental
Arm B - neoadjuvant chemotherapy 		Part of randomisation 1. Patients will receive up to 4 cycles of Paclitaxel, Ifosfamide, and Cisplatin (TIP). Administration on an outpatient basis: Paclitaxel 175 mg/m2, day 1, Ifosfamide 900 mg/m2, days 2-5, Cisplatin 15 mg/m2, days 1-5 Administration on an inpatient basis: Paclitaxel 175 mg/m2, day 1, Ifosfamide 1200 mg/m2, days 1-3, Cisplatin 25 mg/m2, days 1-3
  • Drug: Paclitaxel
    Dose 175mg/m2 as part of TIP regimen.
    Other names:
    • Taxol
  • Drug: Ifosfamide
    Dose 900mg/m2 as part of TIP regimen.
    Other names:
    • Mitoxana
  • Drug: Cisplatin
    Dose 15mg/m2 as part of TIP regimen (neoadjuvant chemotherapy arm) Dose 40mg/m2 for use concurrently with raditotherapy (chemoradiotherapy arm)
Experimental
Arm C - neoadjuvant chemoradiotherapy 		Part of randomisation 1. Radiotherapy dose is 45Gy in 25 fractions over 5 weeks using 6-10 MV photons to all regions. Concurrent cisplatin 40mg/m2 will be given weekly, subject to GFR>45mls/min.
  • Drug: Cisplatin
    Dose 15mg/m2 as part of TIP regimen (neoadjuvant chemotherapy arm) Dose 40mg/m2 for use concurrently with raditotherapy (chemoradiotherapy arm)
  • Radiation: Intensity modulated radiation treatment (IMRT)
    Treatment with very high energy X-rays (radiotherapy).
Experimental
Arm P - prophylactic PLND 		Part of randomisation 2. Prophylactic pelvic lymph node dissection (PLND) - The total treatment duration is estimated to be over 1 day. Patients who have NOT received neoadjuvant chemoradiotherapy will receive adjuvant chemoradiotherapy: Cisplatin 40mg/m2 will be given weekly, subject to GFR>45mls/min. Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to: 1. Any macroscopic tumour or pathological lymph nodes 2. Electively to external iliac nodes in patient with high disease burden Patients who have had neoadjuvant chemoradiotherapy will have prophylactic PLND alone.
  • Procedure: Prophylactic 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.
No Intervention
Arm Q - Surveillance no prophylactic PLND 		no prophylactic PLND Part of randomisation 2. For patients who have NOT received neoadjuvant chemoradiotherapy: Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to: Any macroscopic tumour or pathological lymph nodes Electively to external iliac nodes in patient with high disease burden

Recruiting Locations

Los Angeles County-USC Medical Center
Los Angeles, California 90033
Contact:
Anne Schuckman
323-865-3700
anne.schuckman@med.usc.edu

USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033
Contact:
Sia Daneshmand
323-865-3700
daneshma@usc.edu

Moffitt Cancer Center
Tampa, Florida 33612
Contact:
Phil Spiess
813-745-8343
Philippe.spiess@moffitt.org

Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
Contact:
Viraj Master
404-778-4898
vmaster@emory.edu

Mayo Clinic
Rochester, Minnesota 55905
Contact:
Lance Pagliaro
pagliaro.lance@mayo.edu

University of Texas M.D. Anderson Cancer Center
Houston, Texas 77030
Contact:
Curtis Pettaway
713-792-3250
cpettawa@mdanderson.org

More Details

NCT ID
NCT02305654
Status
Recruiting
Sponsor
Institute of Cancer Research, United Kingdom

Study Contact

UK - InPACT Senior Trial Manager
02087224261
InPACT-icrctsu@icr.ac.uk

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.