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

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ClinicalTrials.gov Identifier: NCT02305654
Recruitment Status : Recruiting
First Posted : December 2, 2014
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
ECOG-ACRIN Cancer Research Group
Canadian Cancer Trials Group
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

Brief Summary:

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 or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Penis, Usual Type Procedure: ILND - Inguinal Lymph Node Dissection Drug: Paclitaxel Drug: Ifosfamide Drug: Cisplatin Radiation: Intensity modulated radiation treatment (IMRT) Procedure: Prophylactic PLND - pelvic lymph node dissection Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)
Actual Study Start Date : May 12, 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Taxol

Drug: Ifosfamide
Dose 900mg/m2 as part of TIP regimen.
Other Name: 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




Primary Outcome Measures :
  1. Overall survival [ Time Frame: up to 5 years ]
    The primary outcome measure that will be measured for all trial patients is survival time. This is 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 :
  1. Disease specific survival time [ Time Frame: up to 5 years ]
    Disease-specific survival time which is defined in whole days as the time from the date of randomisation to the date of death specifically from disease; 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. Number of patients experience a grade 3 or 4 toxicity [ Time Frame: up to 5 years ]
  3. Disease-free survival time [ Time Frame: up to 5 years ]

    Disease-free survival time (DFST) which is defined in whole days as the time from date of randomisation to the date of either locoregional recurrence, distant metastasis or death from disease, whichever occurs first; for those who have not been reported as experiencing any of these events, the DFST 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.

    Subsidiary outcome measures will be

    • locoregional recurrence free survival time (LRFST).
    • distant metastases free survival time (DMFST).
    • 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. Occurrence of surgical complication [ Time Frame: up to 5 years ]
  5. Is it possible to achieve pathological nodal assessment after chemotherapy [ Time Frame: 12 weeks ]
    Feasibility of pathological nodal assessment after chemotherapy which is recorded as whether or not it was possible to achieve a pathological nodal assessment after chemotherapy.

  6. Quality of life [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24 and 36 months ]
    Measured using the EORTC-QLQC30 and Lymphodema-QL

  7. Occurrence of Pathological complete remission [ Time Frame: Time to complete remission after randomisation ]

    Measured for all patients in InPACT-neoadjuvant:

    Absolute absence of disease on histological examination


  8. Operability [ Time Frame: 2-6 weeks ]
    Measured for all trial patients in InPACT-neoadjuvant. Operability which will be recorded as whether or not the planned inguinal node dissection was undertaken and the reasons if it did not occur.

  9. Occurrence of Lower limb/scrotal oedema [ Time Frame: up to 5 years ]
    Occurrence of Lower limb/scrotal oedema which is recorded as whether or not the patient experiences a lower limb or scrotal oedema

  10. On-schedule delivery of neoadjuvant therapy [ Time Frame: After randomisation up to 12 weeks ]
    Feasibility of on-schedule delivery of neoadjuvant therapy


Other Outcome Measures:
  1. Acceptability of randomisation [ Time Frame: up to 5 years ]
    In addition to the outcome measures, the acceptability of both randomisations will be monitored based on the proportion of eligible patients approached for randomisation, the proportion of approached patients consenting to randomisation and the proportion of randomised patients receiving their allocated treatment. This will provide ongoing information regarding the feasibility of the trial successfully completing to target.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02305654


Contacts
Contact: InPACT Senior Trial Manager 02087224261 InPACT-icrctsu@icr.ac.uk
Contact: InPACT Trial Manager 02087224513 InPACT-icrctsu@icr.ac.uk

Locations
United Kingdom
The Royal Marsden NHS Foundation Trust Recruiting
London, United Kingdom, SM2 5PT
Contact: Dr Alison Tree         
St George's Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SW17 0QT
Contact: Mr Nick Watkin         
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
ECOG-ACRIN Cancer Research Group
Canadian Cancer Trials Group
Investigators
Study Chair: Steve Nicholson Imperial College Healthcare NHS Trust
Study Chair: Curtis Pettaway MDACC

Additional Information:
Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT02305654     History of Changes
Other Study ID Numbers: ICR CTSU/2014/10048
CRUK/13/005 ( Other Grant/Funding Number: Cancer Research UK )
First Posted: December 2, 2014    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Institute of Cancer Research, United Kingdom:
Penis cancer
Chemotherapy
Chemoradiotherapy
Surgery
Phase III

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Paclitaxel
Isophosphamide mustard
Albumin-Bound Paclitaxel
Cisplatin
Ifosfamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents