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

• ClinicalTrials.gov Identifier: NCT02305654
• Recruitment Status: Recruiting
• First Posted: December 2, 2014
• Last Update Posted: February 6, 2023
• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: National Cancer Institute (NCI); ECOG-ACRIN Cancer Research Group
• Information provided by (Responsible Party): Institute of Cancer Research, United Kingdom

Tracking Information

• First Submitted Date: September 23, 2014
• First Posted Date: December 2, 2014
• Last Update Posted Date: February 6, 2023
• Actual Study Start Date: May 12, 2017
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 27, 2014)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 27, 2014)

• 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.
• Number of patients experience a grade 3 or 4 toxicity [ Time Frame: up to 5 years ]
• 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.
• Occurrence of surgical complication [ Time Frame: up to 5 years ]
• 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.
• Quality of life [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24 and 36 months ]
  Measured using the EORTC-QLQC30 and Lymphodema-QL
• 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
• 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.
• 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
• On-schedule delivery of neoadjuvant therapy [ Time Frame: After randomisation up to 12 weeks ]
  Feasibility of on-schedule delivery of neoadjuvant therapy

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 27, 2014)

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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)
• Official Title: International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma of the Penis, Usual Type

Intervention

• Procedure: ILND - Inguinal Lymph Node Dissection
  Surgery to remove the lymph nodes in the groin near to where the cancer first appeared.
• 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)
• Radiation: Intensity modulated radiation treatment (IMRT)
  Treatment with very high energy X-rays (radiotherapy).
• 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.

Study Arms

• 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.

  Intervention: Procedure: ILND - Inguinal Lymph Node Dissection
• 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

  Interventions:

  • Drug: Paclitaxel
  • Drug: Ifosfamide
  • Drug: Cisplatin
• 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.

  Interventions:

  • Drug: Cisplatin
  • Radiation: Intensity modulated radiation treatment (IMRT)
• 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.

  Intervention: Procedure: Prophylactic PLND - pelvic lymph node dissection
• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 2, 2023): 200
• Original Estimated Enrollment (submitted: November 27, 2014): 400
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: UK - InPACT Senior Trial Manager; 02087224261; InPACT-icrctsu@icr.ac.uk

Contact: US/Canada - InPACT DA for EA8134; (857)504-2900

• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT02305654
• Other Study ID Numbers: ICR CTSU/2014/10048; CRUK/13/005 ( Other Grant/Funding Number: Cancer Research UK ); 13580965 ( Registry Identifier: ISRCTN ); EA8134 ( Other Grant/Funding Number: NCI ); IRCI004 ( Other Identifier: IRCI ); 2015-001199-23 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Institute of Cancer Research, United Kingdom
• Original Responsible Party: Same as current
• Current Study Sponsor: Institute of Cancer Research, United Kingdom
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• ECOG-ACRIN Cancer Research Group

Investigators

• Study Chair: Steve Nicholson; Mid and South Essex NHS Foundation Trust
• Study Chair: Curtis Pettaway; University of Texas M.D. Anderson Cancer Center ; 713-792-3250 ; cpettawa@mdanderson.org

• PRS Account: Institute of Cancer Research, United Kingdom
• Verification Date: February 2023