An international study looking at the treatment of cancer of the penis that has spread to inguinal or pelvic lymph nodes

ISRCTN	ISRCTN13580965
DOI	https://doi.org/10.1186/ISRCTN13580965
EudraCT/CTIS number	2015-001199-23
IRAS number	168344
ClinicalTrials.gov number	NCT02305654
Secondary identifying numbers	CPMS 32594

Submission date: 05/06/2017
Registration date: 13/09/2017
Last edited: 13/05/2025

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-treatment-of-cancer-of-the-penis-that-has-spread-to-the-lymph-nodes-inpact

Study website

Contact information

Ms Stephanie Burnett
Public

The Institute of Cancer Research
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom

Phone	+44 (0)20 8722 4261
Email	inpact-icrctsu@icr.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment, Drug, Radiotherapy, Surgery
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	InPACT - International Penile Advanced Cancer Trial (International Rare Cancer Initiative)
Study acronym	InPACT
Study objectives	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(s)	London Riverside ethics committee, 17/10/2016, ref: 16/LO/1355
Health condition(s) or problem(s) studied	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
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 study start date	01/02/2011
Completion date	30/11/2027

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	Planned Sample Size: 200; UK Sample Size: 49
Key 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
Key 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)
Date of first enrolment	15/05/2017
Date of final enrolment	31/05/2025

Locations

Countries of recruitment

England
United Kingdom
Wales

Study participating centres

St George’s Hospital

Blackshaw Road
London
SW17 0QT
United Kingdom

The Royal Marsden Hospital

Downs Road
Sutton
SM2 5PT
United Kingdom

Leicester General Hospital

Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Norfolk and Norwich University Hospital

Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom

Velindre Hospital

Velindre Road
Cardiff
CF14 2TL
United Kingdom

Morriston Hospital

Heol Maes Eglwys
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom

Sponsor information

Institute of Cancer Research
Research organisation

The Institute of Cancer Research
Clinical Trials & Statistics Unit (ICR-CTSU)
London
SM2 5NG
United Kingdom

Website	https://www.icr.ac.uk/our-research/centres-and-collaborations/centres-at-the-icr/clinical-trials-and-statistics-unit/clinical-trials/inpact
"ROR"	https://ror.org/043jzw605

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2028
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	The main trial results will be published in peer reviewed scientific journals on behalf of all collaborators.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from inpact-icrctsu@icr.ac.uk.

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications	01/06/2019	10/05/2022	Yes	No
HRA research summary		28/06/2023	No	No
Other publications	01/04/2025	13/05/2025	Yes	No

Editorial Notes

13/05/2025: The following changes were made to the trial record:
1. Publication reference added.
2. UK recruitment closes 31/05/2025 however the trial is international, and recruitment in the USA continues to 31/05/2026.
03/06/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2024 to 31/05/2025.
2. The overall end date was changed from 31/05/2026 to 30/11/2027.
3. The intention to publish date was changed from 31/05/2025 to 31/12/2028.
10/05/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 15/05/2022 to 31/05/2024.
2. The intention to publish date was changed from 15/05/2023 to 31/05/2025.
3. Publication reference and IRAS number added.
4. Sponsor details updated.
5. The target number of participants was changed from 'Planned Sample Size: 400; UK Sample Size: 200' to 'Planned Sample Size: 200; UK Sample Size: 49'.
6. Leicester General Hospital, Norfolk and Norwich University Hospital, Velindre Cancer Centre and Morriston Hospital were added as trial participating centres.
20/09/2021: Internal review.
24/04/2019: The following changes have been made:
1. The clinicaltrials.gov number has been added.
2. Anna Kerek's details have been removed from the trial contacts.
03/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Testicular Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of male genital organs" to "Penis cancer" following a request from the NIHR.
16/10/2018: Cancer Help UK lay summary link added to plain English summary field.
16/10/2017: Internal review.