Plain English Summary
Trial website
Contact information
Type
Public
Primary contact
Ms Stephanie Burnett
ORCID ID
Contact details
The Institute of Cancer Research
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom
+44 (0)20 8722 4261
inpact-icrctsu@icr.ac.uk
Additional identifiers
EudraCT number
2015-001199-23
ClinicalTrials.gov number
NCT02305654
Protocol/serial number
32594
Study information
Scientific title
InPACT - International Penile Advanced Cancer Trial (International Rare Cancer Initiative)
Acronym
InPACT
Study hypothesis
The aim of the study is to examine the combination and sequence of four treatments for men with locally advanced penis cancer. The study will assess whether ILND surgery after neoadjuvant chemotherapy or chemoradiotherapy is better than surgery alone, and whether there is any added benefit from removing the pelvic lymph nodes or not.
Ethics approval
London Riverside ethics committee, 17/10/2016, ref: 16/LO/1355
Study design
Randomised; Interventional; Design type: Treatment, Drug, Radiotherapy, Surgery
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Penis cancer
Intervention
Patients will receive up to 4 treatments in different sequences. Randomisation process: Sequential randomisation by minimisation.
Treatment 1: Inguinal lymph node dissection (ILND)
Methodology: Standard of care surgery performed utilizing open approach
Total duration of treatment: 1 day
Treatment 2: Chemotherapy
Methodology: neoadjuvant chemotherapy before surgery (ILND)
Generic drug name: Paclitaxel, Ifosfamide, Cisplatin (TIP)
The dosage given: Paclitaxel 175 mg/m²/cycle, Ifosfamide 3600 mg/m²/cycle, Cisplatin 75 mg/m²/cycle
Method of administration: Intravenous infusion
Frequency of administration: The inpatient regimen of TIP is administered over 3 days repeated in 21-day cycles. The outpatient regimen is administered over 5 days repeated in 21-day cycles
Total duration of treatment: 12 weeks (4 21-day cycles)
Treatment 3: Chemoradiotherapy
Methodology: neoadjuvant chemoradiotherapy before surgery (ILND) OR adjuvant chemoradiotherapy after pelvic lymph node dissection
Generic drug name: Cisplatin
The dosage given: Concurrent cisplatin at 40 mg/m² weekly
Radiotherapy in the neoadjuvant setting: the radiotherapy dose is 45Gy in 25 fractions over 5 weeks using 6-10 MV photons to all regions.
Radiotherapy in the adjuvant setting:
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: 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
Method of administration: Concurrent cisplatin is given via intravenous infusion. Radiotherapy is to be delivered with either a forward planned IMRT technique or inverse planned IMRT, performed using the local treatment planning system. Rotational arc therapies are permitted (Rapid Arc™, VMAT™ and Tomotherapy™).
Frequency of administration: Concurrent cisplatin is given once a week, radiotherapy is given 5 days a week
Total duration of treatment: 5 weeks
Treatment 4: Pelvic lymph node dissection
Methodology: prophylactic pelvic lymph node dissection perforemed utilizing open, laparoscopic or robot-assisted laparoscopic approaches
Total duration of treatment: 1 day
Follow-up: All patients will undergo clinical review in accordance with the guidelines of the European Association of Urology (EAU), namely every 3 months for years 1 and 2, then every 6 months for years 3, 4 and 5, from the start of their treatment
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
Survival time, 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 outcome measures
Secondary outcome measures for all patients:
1. Disease-specific survival time, defined in whole days as the time from the date of randomisation to the date of death specifically from penis cancer; 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
2. Disease-free survival time (DFS), defined in whole days as the time from date of randomisation to the date of either locoregional recurrence, distant metastasis or death from penis cancer, whichever occurs first; for those who have not been reported as experiencing any of these events, the DFS time 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. A subsidiary outcome measure will be locoregional recurrence free survival time (LRFST) which is defined in whole days as the time from date of randomisation to the date of locoregional recurrence; for those who have not been reported with this event, the LRFST will be censored at the date last known to be alive and free of disease
3. A subsidiary outcome measure will be distant metastases free survival time (DMFST), defined in whole days as the time from date of randomisation to the date of distant metastasis or death from disease, whichever occurs first; for those who have not been reported as experiencing either of these events, the DMFST will be censored at the date last known to be alive and free of distant metastasis or date of non-disease-specific death. 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
4. Toxicity; all events experienced by patients are recorded and graded using CTCAE Version 4 criteria and specifically the occurrence of at least one grade 3 or 4 event
5. Occurrence of surgical complications, recorded as whether or not a surgical complication was experienced according to the Modifed Clavien-Dindo Classification criteria
6. Feasibility of pathological nodal assessment after chemotherapy, recorded as whether or not it was possible to achieve a pathological nodal assessment after chemotherapy
7. Quality of life (in participating patients), measured using the EORTC-QLQC30 and Lymphodema-QL on 8 occasions: prior to randomisation, 3-monthly during year 1, 6-monthly during year 2, and at the end of year 3
Secondary outcome measures measured for all trial patients in InPACT-neoadjuvant:
1. Occurrence of pathological complete remission, defined as an absolute absence of disease on histological examination in accordance with the Royal College of Pathologists’ guidelines
2. Operability, recorded as whether or not the planned inguinal node dissection was undertaken and the reasons if it did not occur
3. Feasibility of on-schedule delivery of neoadjuvant therapy
Secondary outcome measures for all trial patients in InPACT-pelvis:
1. Occurrence of lower limb/scrotal oedema, recorded as whether or not the patient experiences a lower limb or scrotal oedema according to CTCAE Version 4 criteria
Overall trial start date
01/02/2011
Overall trial end date
31/05/2026
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male, aged 18 years or older
2. Histologically-proven squamous cell carcinoma of the penis
3. Stage:
3.1. Any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or
3.2. Any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0 or
3.3. Any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy), M0
4. Measurable disease as determined by RECIST (version 1.1) criteria
5. Performance Status ECOG 0, 1 or 2
6. Patient is fit to receive the randomisation options for which he is being considered
7. Haematology/biochemistry (as dictated by local hospital practice) should indicate fitness for randomisation options and parameters should be in line with considerations specified in the summary of product characteristics. Haematological parameters should not be supported by transfusion to enable entry into the trial. Liver function and renal function tests must form part of the pre-treatment assessment for patients who may be randomised to receive TIP chemotherapy e.g. patients with impaired renal function may not be considered for arms B and C of InPACT-neoadjuvant but may be considered for arm A
8. Willing and able to comply with follow-up schedule
9. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
Planned Sample Size: 400; UK Sample Size: 200
Participant exclusion criteria
Patients who have any of the following are not eligible:
1. Pure verrucous carcinoma of the penis
2. Non-squamous malignancy of the penis
3. Squamous carcinoma of the urethra
4. Stage M1
5. Previous chemotherapy or chemoradiotherapy outside of the InPACT trial
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
7. Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile)
Recruitment start date
15/05/2017
Recruitment end date
15/05/2022
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St George’s Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom
Trial participating centre
The Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom
Funders
Funder type
Charity
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The main trial results will be published in peer reviewed scientific journals on behalf of all collaborators.
IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from inpact-icrctsu@icr.ac.uk.
Intention to publish date
15/05/2023
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list