InPACT

Phase 1

• Conditions: ocally advanced squamous carcinoma of the penis; MedDRA version: 20.0Level: PTClassification code 10034299Term: Penile cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001199-23-GB
• Lead Sponsor: The Institute of Cancer Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-24
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 400

Inclusion Criteria

Inclusion criteria for InPACT-neoadjuvant
1.Male, aged 18 years or older.
2.Histologically-proven squamous cell carcinoma of the penis.
3.Stage:
- any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node OR a single radiologically-abnormal inguinal lymph node with no evidence of extra-nodal extension), M0 or;
- any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes OR radiologically evident multiple or bilateral inguinal nodes with no evidence of extra-nodal extension), M0 or;
- any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy), M0
4.Patients being considered for InPACT-neoadjuvant must have either:
- measurable disease as determined by RECIST (version 1.1) criteria or;
- a single, unilateral lymph node that does not meet RECIST criteria for measurable disease, but that is either palpable or radiologically abnormal, and with histological/cytological evidence of metastatic involvement. This applies only to low disease burden patients who would then be eligible for direct entry into arm A.
*Patients with radiological evidence of macroscopic pelvic node involvement are eligible for randomisation in InPACT-neoadjuvant but are not be eligible for entry into InPACT-pelvis.
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 (see section 5.5.2 of the protocol for full details) but may be considered for arm A.
8.Nodal disease burden must be assessable, with all patients stratified into one of three categories (low / intermediate / high disease burden) in accordance with physical examination and Graafland radiological criteria (see Section 5.5.1).
9.Glomerular filtration rate (GFR) must be assessed for all patients (see Section 5.5.2). Requirements for GFR vary with treatment eligibility:-
-GFR =50 mL/min: eligible for all treatment options
-GFR 45–49 mL/min: eligible for surgery alone (arm A) and for synchronous chemoradiotherapy (arm C); not eligible for neoadjuvant TIP chemotherapy
-GFR < 45 mL/min eligible for surgery alone (arm A) or radiotherapy (arm C with cisplatin omitted)
10.Willing and able to comply with follow-up schedule.
11.Written informed consent.

Inclusion criteria for InPACT-pelvis
1.Patient has met eligibility criteria for InPACT-neoadjuvant.
2.Patient has completed ILND within arms A, B or C of InPACT-neoadjuvant.
3.There must be no radiological evidence of residual inguinal disease on cross-sectional imaging performed after therapeutic inguinal lymph node dissection.
4.There must be no radiological evidence of pelvic lymphadenopathy on cross-sectional imaging performed after therapeutic inguinal lymph node dissection.
*Any patient who underwent synchronous ispilateral pelvic lymph node dissection at the time of inguinal lymph node dissection is automatically ineligible for InPACT Pelvis.
5.Patient must be at

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.Any absolute contraindication to chemotherapy if eligible for a chemotherapy/chemoradiotherapy randomisation.
7.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.
8.Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile).
9.Radiological evidence of macroscopic pelvic lymph node disease on post-ILND cross-sectional imaging
10.Patients with regionally advanced (N1-3, M0) penile cancer with disease burden that is considered unresectable by the accredited InPACT surgeon* utilising standard inguinal, ilioinguinal lymphadenectomy resection and reconstructive techniques. For example, where procedures would require circumferential resection of the femoral or iliac vessels, or the requirement for hemipelvectomy.
* InPACT surgeon should consider reviewing the case with their National InPACT surgical lead where resectablity is unclear.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified