Paclitaxel/Ifosfamide/Cisplatin Chemotherapy for High Risk Pediatric Germ Cell Tumor

Non-randomized, Phase II, Open-label Study for Efficacy and Safety of Consolidation Paclitaxel/Ifosfamide/Cisplatin (TIP) Chemotherapy for High Risk Pediatric Germ Cell Tumor

Germ cell tumor has generally good prognosis, but high risk germ cell tumor has still very poor prognosis. There remains the need of further improvement with other chemotherapy strategy. Especially more than 11 years old, mediastinal germ cell tumor, stage 3 or 4 extragonodal germ cell tumor or the remained tumor after the primary treatment are the group with the poorest prognosis.

Paclitaxel is widely used chemotherapeutic agent in adults and the experience of the agent has also been accumulated in children. The paclitaxel, ifosfamide, cisplatin (TIP) regimen has been used 2nd-line treatment for germ cell tumor and there is some promising result of the role of TIP in first line germ cell tumor treatment. In high risk pediatric germ cell tumor patients, TIP regimen will be able to reduce lung toxicity from the bleomycin as the standard regimen and to improve the survival. In this trial, the efficacy and safety of TIP as the first line treatment for germ cell tumor will be elucidated.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Germ Cell Tumor
• Intervention / Treatment: Drug: TIP treatment (paclitaxel/ifosfamide/cisplatin)

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jung Woo Han; Phone Number: 82-2-2228-2050; Email: JWHAN@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Jung Woo Han; Phone Number: 82-2-2228-2050; Email: JWHAN@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Over 1 year old and less than 20 years old
• Pathologically or cytologically diagnosed germ cell tumor
• Germ cell tumor which has not been treated previously
• Higher than stage II (stage I should be excluded)

• Pathologic type

  1. embryonal carcinoma
  2. choriocarcinoma
  3. yolk sac tumor
  4. teratoma with malignant germ cell tumor elements

• High risk definition

  1. More than 11 years old, male or female

  2. Less than 11 years old, male or female

     1. Extragonodal germ cell tumor, stage III
     2. Extragonodal germ cell tumor, stage IV
     3. Ovarian germ cell tumor, stage IV
• More than 8 weeks of life expectancy
• performance level : ECOG Performance score 0, 1, or 2
• informed consent should be obtained

Exclusion Criteria:

• pregnancy or lactating patients (fertile men or women should agree to avoid pregnancy during the trial period)
• previously reported allergy or hypersensitivity to trial chemotherapeutic agent
• severe hypersensitivity to the agent containing Cremophor R EL (polyoxyethylated castor oil)

• Acceptable organ functions

  1. Bone marrow : Absolute neutrophil count >=1000/µL , platelet >= 100000/µL
  2. Renal function : serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  3. Hepatic function : total bilirubin ≤ 1.5 x ULN, ALT ≤ 3.0 x UNL
  4. Cardiac Function : Ejection fraction ≥ 50%
  5. Uncontrolled infection
  6. Uncontrolled urinary obstruction
  7. Uncontrolled cystitis

• Followings will be excluded

  1. Mature teratoma
  2. Gliomatosis Peritonei
  3. Low Risk Germ Cell Tumor
  4. testicular stage I
  5. ovarian stage I
  6. recurrent, refractory tumor
• Concomitant other trial agent beside the agents in this trial

• Concomitant chemotherapeutic agents besides the agents in this trial

  1. Concomitant tumor other than germ cell tumor
  2. Other trial agents
  3. Other chemotherapeutic agents

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: TIP treatment arm	Drug: TIP treatment (paclitaxel/ifosfamide/cisplatin); Paclitaxel 240mg/m2/day D1 (total 240mg/m2) Ifosfamide 1.5g/m2/day D2~5 (total 6g/m2) Cisplatin 25mg/m2/day D2~5 (total 100mg/m2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete Response Rate	12weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	3 years
Overall Response Rate	12 weeks and 18 weeks
Complete Response Rate	18 weeks
Event Free Survival	3 years

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Jung Woo Han, Department of Pediatric Hematology and Oncology, Yonsei Cancer Center, Yonsei University Health System.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2020
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2028

Study Registration Dates

• First Submitted: July 8, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; 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: 4-2020-0658

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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