TIP Regimen Combined With Triplizumab Neoadjuvant Therapy for Locally Advanced Penile Cancer

A Single-center, Single-arm Clinical Study of TIP(Paclitaxel + Ifosfamide + Cisplatin) Regimen Combined With Triplizumab Neoadjuvant Therapy for Locally Advanced Penile Cancer

Primary Objective: To evaluate the efficacy and safety of TIP (paclitaxel + ifosfamide + cisplatin) combined with Toripalimab as a neoadjuvant treatment in locally advanced penile cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Penile Cancer
• Intervention / Treatment: Drug: Paclitaxel + Ifosfamide + Cisplatin & Toripalimab

Detailed Description

Penile cancer is a rare malignant tumor, which often occurs in the inner plate of the prepuce and glans. Squamous cell carcinoma is the most common pathological type. Lymph node metastasis is a crucial factor that leads to poor prognosis of penile cancer. The 5-year OS of penile cancer patients without lymph node metastasis is 90%. Still, it goes down sharply in patients with inguinal lymph node metastasis and pelvic lymph node metastasis, which is 50% and 0%, respectively. Using neoadjuvant chemotherapy to treat patients with locally advanced penile cancer (T4, any N stage, or any T stage, N3) may improve their prognosis. TIP (Paclitaxel + Ifosfamide + Cisplatin) regimen is the first-line neoadjuvant treatment recommended by NCCN guidelines. PD-1 is an immune checkpoint molecule on the surface of T cells. In recent years, immune checkpoint inhibitors targeting PD-1 have shown good efficacy in a variety of tumors. Some phase II / III clinical trials have shown that PD-1 inhibitors can improve the prognosis of patients with lung squamous cell carcinoma, head and neck squamous cell carcinoma, and cervical cancer. Previous studies have found that PD-L1 is highly expressed in 40% - 60% of penile cancer, suggesting that penile cancer patients may benefit from immunotherapy. The management of penile cancer with lymph node metastasis is difficult, especially for the N2-3 stage. This phase II study aims to explore an effective combination therapy for locally advanced penile cancer. 25 patients need to be enrolled.TIP & toripalimab will be administered every 21 days until surgery, evidence of disease progression, or onset of unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hui Han; Phone Number: +86 13002018798; Email: hanhui@sysucc.org.cn
• Study Contact Backup: Name: Ting Xue; Phone Number: +86 18243057370; Email: xueting1@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Squamous cell carcinoma confirmed by histology or cytology;
2. Clinical Stage is Locally advanced penile cancer (T4, any N stage; or any T stage, N3);
3. No prior chemotherapy for newly diagnosed or relapsed patients or the time from the last chemotherapy to relapse should be longer than 12 months;
4. There is at least one measurable lesion according to the solid tumor efficacy evaluation standard RECIST1.1;
5. the Eastern Cooperative Oncology Group (ECOG) scored 0-2;
6. Blood marrow function: Hemoglobin(Hb) >/= 80g/L; White blood cell count >/= 3.0x10^9/L; Neutrophil count >/= 1.5x10^9/L; Platelet count >/ = 100x10^9/L;
7. Liver function: AST, ALT, ALP </= 2.5 ULN; Total bilirubin </= 1.5 ULN;
8. Estimated survival >/= 12 months;
9. No prior serious disease history of a systemic organ;
10. The participant understands this study procedure and signs the informed consent.

Exclusion Criteria:

1. Peripheral neuropathy degree >/=2 (affecting patient's function);
2. Previously received any other experimental drug treatment within 4 weeks before enrollment;
3. Patients with other cancer at present, or have other malignant tumor histories within the past 5 years. Except for (1) Cured skin non-malignant melanoma; (2) Curable tumor, including low-risk prostate cancer (T1a, Gleason score<6, PSA<0.5ng/ml), superficial bladder cancer and so on; (3) Other solid tumors have received radical treatment, and no recurrence or metastasis has been found at least 5 years;
4. Other serious or poorly controlled concomitant diseases, including but not limited to (1) Severe or acute attack disease history of cardiovascular, liver, respiratory, kidney, blood, endocrine or neuropsychiatric system within 6 months; (2) Active infection history and needed antibiotic treatment within 2 weeks before enrollment; (3) Congestive heart failure (grade III-IV); (4) Unstable angina pectoris or myocardial infarction history within 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Neoadjuvant Therapy TIP (Paclitaxel + Ifosfamide + Cisplatin) & Toripalimab; Drug: Toripalimab 240mg, ivgtt, d1 Drug: Paclitaxel 175 mg/m2, ivgtt, d1 Drug: Cisplatin 25mg/m2·d, ivgtt, d1-3 Drug: Ifosfamide 1.2g/m2·d, ivgtt, d1-3	Drug: Paclitaxel + Ifosfamide + Cisplatin & Toripalimab; Paclitaxel + Ifosfamide + Cisplatin & Toripalimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate (ORR) based on RECIST 1.1 criteria.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	Percentage of Participants With Pathologically Complete Response	12 weeks
EFS	Event-free survival, EFS	2 months
OS	Overall Survival	6 months
Adverse events	Number of participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)	2 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Penile Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Penile Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Paclitaxel; Ifosfamide
• Other Study ID Numbers: B2024-043-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No