## Protocol Section
### Identification Module
**NCT ID:** NCT06415318

**Brief Title:** TIP Regimen Combined With Triplizumab Neoadjuvant Therapy for Locally Advanced Penile Cancer

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

#### Organization Study ID Info
**ID:** B2024-043-01
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2027-12-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-10

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** ZHOU FANGJIAN

**Investigator Title:** Director

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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

**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.

### Conditions Module

**Conditions:**

- Penile Cancer

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 25

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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

**Intervention Names:**

- Drug: Paclitaxel + Ifosfamide + Cisplatin & Toripalimab

**Label:** Experimental: Neoadjuvant Therapy TIP (Paclitaxel + Ifosfamide + Cisplatin) & Toripalimab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Experimental: Neoadjuvant Therapy TIP (Paclitaxel + Ifosfamide + Cisplatin) & Toripalimab

**Description:** Paclitaxel + Ifosfamide + Cisplatin \& Toripalimab

**Name:** Paclitaxel + Ifosfamide + Cisplatin & Toripalimab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Objective Response Rate (ORR) based on RECIST 1.1 criteria.

**Measure:** ORR

**Time Frame:** 6 weeks

#### Secondary Outcomes

**Description:** Percentage of Participants With Pathologically Complete Response

**Measure:** pCR

**Time Frame:** 12 weeks

**Description:** Event-free survival, EFS

**Measure:** EFS

**Time Frame:** 2 months

**Description:** Overall Survival

**Measure:** OS

**Time Frame:** 6 months

**Description:** Number of participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

**Measure:** Adverse events

**Time Frame:** 2 months

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** MALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** hanhui@sysucc.org.cn

**Name:** Hui Han

**Phone:** 13002018798

**Phone Ext:** +86

**Role:** CONTACT

**Contact 2:**

**Email:** xueting1@sysucc.org.cn

**Name:** Ting Xue

**Phone:** 18243057370

**Phone Ext:** +86

**Role:** CONTACT

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005834

- Term: Genital Neoplasms, Male

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000005832

- Term: Genital Diseases, Male

- ID: D000091662

- Term: Genital Diseases

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000010409

- Term: Penile Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M13323

- Name: Penile Neoplasms

- Relevance: HIGH

- As Found: Penile Cancer

- ID: M8946

- Name: Genital Neoplasms, Male

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8944

- Name: Genital Diseases, Male

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13320

- Name: Penile Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4483

- Name: Penile Cancer

- Relevance: HIGH

- As Found: Penile Cancer

### Condition Browse Module - Meshes

- ID: D000010412

- Term: Penile Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000000972

- Term: Antineoplastic Agents, Phytogenic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000050257

- Term: Tubulin Modulators

- ID: D000050256

- Term: Antimitotic Agents

- ID: D000050258

- Term: Mitosis Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: HIGH

- As Found: Surgery

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M6182

- Name: Cisplatin

- Relevance: LOW

- As Found: Unknown

- ID: M10117

- Name: Ifosfamide

- Relevance: HIGH

- As Found: Rich

- ID: M230811

- Name: Isophosphamide mustard

- Relevance: LOW

- As Found: Unknown

- ID: M26197

- Name: Tubulin Modulators

- Relevance: LOW

- As Found: Unknown

- ID: M26196

- Name: Antimitotic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000017239

- Term: Paclitaxel

- ID: D000007069

- Term: Ifosfamide

### Misc Info Module

- Version Holder: 2024-05-31
