Penile Cancer > Ifosfamide

Multiple Therapies for Advanced Penile Cancer

(InPACT Trial)

Recruiting in Palo Alto (17 mi)

+16 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Institute of Cancer Research, United Kingdom

Disqualifiers: Verrucous carcinoma, Nonsquamous malignancy, others

Stay on your current meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Inguinal Lymph Node Dissection (ILND) for advanced penile cancer?

ILND is used for the treatment of metastatic penile cancer and has been associated with significant morbidity, but recent modifications aim to reduce complications while optimizing cancer outcomes.

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Is inguinal lymph node dissection (ILND) generally safe for humans?

Inguinal lymph node dissection (ILND) often has a high rate of complications, especially wound-related issues, when used for treating penile cancer and other conditions.

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How is the treatment with Ifosfamide and ILND different for advanced penile cancer?

This treatment combines Ifosfamide, a chemotherapy drug, with ILND (inguinal lymph node dissection), a surgical procedure, to target advanced penile cancer. The combination is unique because it addresses both the cancer cells with chemotherapy and the affected lymph nodes surgically, which is important since there is no standard treatment for this rare condition.

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Eligibility Criteria

This trial is for individuals with squamous cell carcinoma of the penis, who have palpable lymph nodes but no distant metastasis (M0), and are in a decent physical state (ECOG 0-2). They must have measurable disease and not have received prior chemo or chemoradiotherapy. Those with pure verrucous carcinoma, urethral cancer, other recent malignancies except certain skin cancers, or non-squamous penile cancer cannot join.

Inclusion Criteria

I have been diagnosed with penile squamous cell carcinoma.

Written informed consent

My cancer is at a stage where it has spread to my lymph nodes but not to other parts of my body.

Exclusion Criteria

I haven't had treatment for cancer other than skin cancer in the last 3 years.

I have had chemotherapy or chemoradiotherapy before.

My cancer has spread to other parts of my body.

Participant Groups

The study tests different sequences of treatments for penile cancer. Patients may receive standard surgery alone (ILND), chemotherapy before surgery (neoadjuvant chemotherapy + ILND), or chemoradiotherapy before surgery (neoadjuvant chemoradiotherapy + ILND). High-risk patients post-ILND may also be randomized to get prophylactic pelvic lymph node dissection or not.

Group I: Arm P - prophylactic PLND Experimental Treatment 1 Intervention

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.

Group II: Arm C - neoadjuvant chemoradiotherapy Experimental Treatment 2 Interventions

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.

Group III: Arm B - neoadjuvant chemotherapy Experimental Treatment 3 Interventions

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

Group IV: Arm Q - Surveillance no prophylactic PLND Active Control 1 Intervention

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

Group V: Arm A - Standard Surgery (ILND) Active Control 1 Intervention

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.

Ifosfamide is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Ifex for:

• Testicular cancer
• Ovarian cancer
• Soft tissue sarcoma
• Ewing's sarcoma
• Non-Hodgkin's lymphoma

🇪🇺 Approved in European Union as Ifex for:

• Testicular cancer
• Ovarian cancer
• Soft tissue sarcoma
• Ewing's sarcoma
• Non-Hodgkin's lymphoma

🇨🇦 Approved in Canada as Ifex for:

• Testicular cancer
• Ovarian cancer
• Soft tissue sarcoma
• Ewing's sarcoma
• Non-Hodgkin's lymphoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Grady Health System Atlanta, GA

Fox Chase Cancer Center Philadelphia, PA

University of Chicago Comprehensive Cancer Center Chicago, IL

University of Texas M.D. Anderson Cancer Center Houston, TX

More Trial Locations

Who Is Running the Clinical Trial?

Institute of Cancer Research, United Kingdom Lead Sponsor

National Cancer Institute (NCI) Collaborator

ECOG-ACRIN Cancer Research Group Collaborator

Canadian Cancer Trials Group Collaborator

References

1. Germany pubmed.ncbi.nlm.nih.gov

Morbidity and risk factors for complications of inguinal lymph node dissection in penile cancer. [2023] To assess the morbidity of inguinal lymph node dissection (ILND) in penile cancer, then to compare this morbidity with that of ILND performed in the context of skin cancer treatment.

2. Germany pubmed.ncbi.nlm.nih.gov

Contemporary inguinal lymph node dissection: minimizing complications. [2021] This review describes the morbidity of inguinal lymph node dissection (ILND) performed as part of the management of penile cancer as well as recent modifications that may reduce the incidence of complications.

3. United States pubmed.ncbi.nlm.nih.gov

Update in the surgical principles and therapeutic outcomes of inguinal lymph node dissection for penile cancer. [2013] Inguinal lymph node dissection (ILND) for the treatment of metastatic penile squamous cell carcinoma (SCC) has historically been associated with significant morbidity. This review addresses the surgical principles and techniques to decrease its perioperative morbidity, while optimizing its oncologic outcomes.

4. United States pubmed.ncbi.nlm.nih.gov

Wound Complication Rates after Inguinal Lymph Node Dissection: Contemporary Analysis of the NSQIP Database. [2023] Inguinal lymph node dissection (ILND) is used for diagnosis and treatment in penile cancer (PC), vulvar cancer (VC), and melanomas draining to the inguinal lymph nodes. However, ILND is often characterized by its morbidity and high wound complication rate. Consequently, we aimed to characterize wound complication rates after ILND.

5. United States pubmed.ncbi.nlm.nih.gov

Management of the lymph nodes in penile cancer. [2010] A comprehensive literature study was conducted to evaluate the levels of evidence (LEs) in publications on the diagnosis and staging of penile cancer. Recommendations from the available evidence were formulated and discussed by the full panel of the International Consultation on Penile Cancer in November 2008. The final grades of recommendation (GRs) were assigned according to the LE of the relevant publications. The following consensus recommendations were accepted. Fine needle aspiration cytology should be performed in all patients (with ultrasound guidance in those with nonpalpable nodes). If the findings are positive, therapeutic, rather than diagnostic, inguinal lymph node dissection (ILND) can be performed (GR B). Antibiotic treatment for 3-6 weeks before ILND in patients with palpable inguinal nodes is not recommended (GR B). Abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI) are not useful in patients with nonpalpable nodes. However, they can be used in those with large, palpable inguinal nodes (GR B). The statistical probability of inguinal micrometastases can be estimated using risk group stratification or a risk calculation nomogram (GR B). Surveillance is recommended if the nomogram probability of positive nodes is .5 [50%] or primary tumor grade 2-3 or T2-T4 or cN1-N2, or with lymphovascular invasion), bilateral ILND should be performed (GR B). ILND can be performed at the same time as penectomy, instead of 2-6 weeks later (GR C). SNB based on the anatomic position can be performed, provided the patient is willing to accept the potential false-negative rate of /=2 nodes on one side, contralateral limited ILND with frozen section analysis can be performed, with complete ILND if the frozen section analysis findings are positive (GR B). If clinically suspicious inguinal metastases develop during surveillance, complete ILND should be performed on that side only (GR B), and SNB or limited ILND with frozen section analysis on the contralateral side can be considered (GR C). Endoscopic ILND requires additional study to determine the complication and long-term survival rates (GR C). Pelvic lymph node dissection is recommended if >/=2 proven inguinal metastases, grade 3 tumor in the lymph nodes, extranodal extension (ENE), or large (2-4 cm) inguinal nodes are present, or if the femoral (Cloquet's) node is involved (GR C). Performing ILND before pelvic lymph node dissection is preferable, because pelvic lymph node dissection can be avoided in patients with minimal inguinal metastases, thus avoiding the greater risk of chronic lymphedema (GR B). In patients with numerous or large inguinal metastases, CT or MRI should be performed. If grossly enlarged iliac nodes are present, neoadjuvant chemotherapy should be given and the response assessed before proceeding with pelvic lymph node dissection (GR C). Antibiotic treatment should be started before surgery to minimize the risk of wound infection (GR C). Perioperative low-dose heparin to prevent thromboembolic complications can be used, although it might increase lymph leakage (GR C). The skin incision for ILND should be parallel to the inguinal ligament, and sufficient subcutaneous tissue should be preserved to minimize the risk of skin flap necrosis (GR B). Sartorius muscle transposition to cover the femoral vessels can be used in radical ILND (GR C). Closed suction drainage can be used after ILND to prevent fluid accumulation and wound breakdown (GR B). Early mobilization after ILND is recommended, unless a myocutaneous flap has been used (GR B). Elastic stockings or sequential compression devices are advisable to minimize the risk of lymphedema and thromboembolism (GR C). Radiotherapy to the inguinal areas is not recommended in patients without cytologically or histologically proven metastases nor in those with micrometastases, but it can be considered for bulky metastases as neoadjuvant therapy to surgery (GR B). Adjuvant radiotherapy after complete ILND can be considered in patients with multiple or large inguinal metastases or ENE (GR C). Adjuvant chemotherapy after complete ILND can be used instead of radiotherapy in patients with >/=2 inguinal metastases, large nodes, ENE, or pelvic metastases (GR C). Follow-up should be individualized according to the histopathologic features and the management chosen for the primary tumor and inguinal nodes (GR B).

6. United States pubmed.ncbi.nlm.nih.gov

Assessment and Reporting of Perioperative Adverse Events and Complications in Patients Undergoing Inguinal Lymphadenectomy for Melanoma, Vulvar Cancer, and Penile Cancer: A Systematic Review and Meta-analysis. [2023] Inguinal lymph node dissection (ILND) plays a crucial role in the oncological management of patients with melanoma, penile, and vulvar cancer. This study aims to systematically evaluate perioperative adverse events (AEs) in patients undergoing ILND and its reporting.

7. Switzerland pubmed.ncbi.nlm.nih.gov

Early wound complications after inguinal lymphadenectomy in penile cancer: a historical cohort study and risk-factor analysis. [2013] Complication rates after inguinal lymph node dissection (ILND) are high. Risk factors for early wound complications after ILND in patients with penile carcinoma have not yet been studied.

8. Netherlands pubmed.ncbi.nlm.nih.gov

Single-port robotic inguinal lymph node dissection: A safe and feasible option for penile cancer. [2022] Inguinal lymph node dissection (ILND) is essential to the accurate staging of advanced penile cancer and in determining prognosis. Open ILND is associated with significant morbidity. The robotic-assisted approach has been described with comparable nodal yield with the advantage of decreased postoperative complications when studied with the multiport robotic platform. This video shows our approach for an ILND with the Intuitive single port (SP) robotic platform.

9. Japan pubmed.ncbi.nlm.nih.gov

[Dramatic response of penile cancer with inguinal lymph node metastases to neoadjuvant chemotherapy with paclitaxel, ifosfamide and cisplatin : a case report]. [2015] Carcinoma of the penis is rare, and the prognosis of penile cancer with inguinal metastases is extremely poor. Standard chemotherapy for advanced penile cancer has not been established because of its rarity. A case of penile cancer with inguinal metastases that responded well to neoadjuvant chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP) is described. A 55-year-old Japanese male visited our hospital for a penile tumor and fixed, 4 cm, right inguinal lymph nodes. Computed tomography and 18F-FDG-PET imaging showed not only right but also left inguinal lymphadenopathy. Penile cancer (clinical stage T3N3M0, 7th edition TNM classification) was diagnosed, and partial penectomy and right inguinal biopsy were performed. The pathological examination revealed squamous cell carcinoma of the penis with right inguinal lymph node metastasis. The inguinal metastases were judged to be unsuitable for radical resection ; and, paclitaxel 60 mg/m2 (day 1), ifosfamide 1,200 mg/m2 (days 1-3), and cisplatin 60 mg/m2 (days 1-3) were given at 3-week intervals as neoadjuvant chemotherapy. After 4 courses of chemotherapy, the inguinal metastases were markedly reduced. He had neutropenia (grade 3) during each course and peripheral neuropathy after 2 courses, but there were no severe complications. The patient underwent bilateral inguinal and pelvic lymphadenectomy after neoadjuvant chemotherapy. Pathological examination revealed no viable cells in the resected specimens. The patient remains alive and well with no evidence of recurrence 8 months after this radical treatment. TIP chemotherapy appears to be effective for advanced penile cancer.