International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study) (InPACT)

Institute of Cancer Research, United Kingdom

Status and phase: Enrolling; Phase 3

Conditions: Squamous Cell Carcinoma of the Penis, Usual Type

Treatments: Procedure: Prophylactic PLND - pelvic lymph node dissection; Procedure: ILND - Inguinal Lymph Node Dissection; Radiation: Intensity modulated radiation treatment (IMRT); Drug: Paclitaxel; Drug: Cisplatin; Drug: Ifosfamide

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT02305654

IRCI004 (Other Identifier)

2015-001199-23 (EudraCT Number)

EA8134 (Other Grant/Funding Number)

CRUK/13/005 (Other Grant/Funding Number)

ICR CTSU/2014/10048

13580965 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 200 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 5 patient groups

Arm A - Standard Surgery (ILND)

Active Comparator group

Description:

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.

Treatment:

Procedure: ILND - Inguinal Lymph Node Dissection

Arm B - neoadjuvant chemotherapy

Experimental group

Description:

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

Treatment:

Drug: Ifosfamide

Drug: Cisplatin

Drug: Paclitaxel

Arm C - neoadjuvant chemoradiotherapy

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Radiation: Intensity modulated radiation treatment (IMRT)

Arm P - prophylactic PLND

Experimental group

Description:

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.

Treatment:

Procedure: Prophylactic PLND - pelvic lymph node dissection

Arm Q - Surveillance no prophylactic PLND

No Intervention group

Description:

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