TIP vs BEP Chemotherapy for Germ Cell Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

92 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the safety and effectiveness of two different drug combinations in patients who have intermediate- and poor-risk germ cell tumors (GCT). One combination of drugs, paclitaxel, ifosfamide and cisplatin (TIP), is experimental. The other combination of drugs, bleomycin, etoposide and cisplatin (BEP), is the standard of care treatment for intermediate- and poor-risk germ cell tumors. However, BEP does not cure every patient and therefore newer treatments are needed.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on any chemotherapy or cytotoxic therapy, you would need to stop those to participate in this trial.

What data supports the effectiveness of the TIP chemotherapy treatment for germ cell cancer?

Research shows that TIP chemotherapy (paclitaxel, ifosfamide, and cisplatin) can lead to complete or partial remission in a significant number of patients with metastatic germ cell cancer who did not respond to initial BEP treatment, with a favorable response rate of 60% and a one-year survival rate of 70%. ^{1 2 3 4 5}

Is the TIP vs BEP chemotherapy regimen safe for treating germ cell cancer?

The TIP (paclitaxel, ifosfamide, cisplatin) and BEP (bleomycin, etoposide, cisplatin) chemotherapy regimens have been studied for safety in treating germ cell cancer. TIP was generally well-tolerated with no life-threatening toxicity observed, and BEP with added paclitaxel showed minimal neurosensory issues and no severe neurotoxicity. Both regimens had manageable side effects, such as myelosuppression (reduced bone marrow activity) and diarrhea. ^{6 7 8 9 10}

How does TIP chemotherapy differ from other treatments for germ cell cancer?

TIP chemotherapy, which includes paclitaxel, ifosfamide, and cisplatin, is used as a second-line treatment for germ cell cancer when the standard BEP regimen (bleomycin, etoposide, and cisplatin) fails. It is unique because it can achieve complete remission in patients who do not respond to initial treatments, offering a potential cure for those with resistant or relapsed cancer. ^{1 2 6 7 11}

Research Team

Darren R. Feldman

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with intermediate- or poor-risk germ cell tumors who haven't had chemotherapy, except possibly one or two cycles for stage I seminoma. They should have measurable disease and agree to use contraception. Exclusions include pregnant individuals, those unable to follow the protocol, concurrent serious illnesses, other cancers (except non-melanoma skin cancer), HIV patients on HAART therapy, and active infections.

Inclusion Criteria

I had radiation for germ cell tumor but my cancer is still growing.

I have been recently diagnosed with germ cell tumor (GCT).

My doctor says I've recovered from my last surgery.

Exclusion Criteria

I currently have an active infection.

I have not had chemotherapy, except possibly 1-2 cycles of carboplatin for stage I seminoma.

I have no other cancers except for non-melanoma skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the TIP or BEP chemotherapy regimen for germ cell tumors

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

3 years

Treatment Details

Interventions

• Cisplatin
• Etoposide
• Ifosfamide
• Mesna
• Paclitaxel

Trial Overview The trial compares two drug combinations for germ cell tumors: TIP (paclitaxel, ifosfamide, cisplatin) which is experimental; versus BEP (bleomycin, etoposide, cisplatin), the current standard treatment. The goal is to determine which combination is safer and more effective.

Participant Groups

Group I: Paclitaxel, Ifosfamide and Cisplatin (TIP) Experimental Treatment 4 Interventions

Paclitaxel 120 mg/m2 IV over 120-180 min Days 1 and 2 (+/- 4 days)\* Mesna 120 mg/m2 IV (duration of infusion per institutional guidelines) approximately 30 minutes prior to initiation of ifosfamide Days 1-5 (+/- 4 days)\* Ifosfamide 1200 mg/m2 IV over approximately 60 to 120 min Days 1-5 or per institutional guidelines (mixed 1:1 with mesna) (+/- 4 days)\* Mesna\*\* 1200 mg/m2 IV over approximately 60-120 min or per institutional guidelines (mixed 1:1 with ifosfamide)(+/- 4 days)\* Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5 (+/- 4 days)\* \*\*Additional mesna may be given at the discretion of the investigator \*Paclitaxel or Ifosfamide or Mesna or Cisplatin or any combination of these agents can be held as needed for patient safety on a given day between days 1-5 but must be made up within 4 days to avoid a protocol violation.

Group II: Bleomycin, Etoposide and Cisplatin (BEP) Active Control 3 Interventions

Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5 (+/- 4 days)\* Etoposide 100 mg/m2 IV over approximately 1 hour Days 1-5 (+/- 4 days)\* Bleomycin 30 U flat dose IV push Days 2, 8 and 15 (all +/- 4 days) \*Etoposide or Cisplatin or both can be held as needed for patient safety on a given day between days 1-5 but must be made up within 4 days to avoid a protocol violation.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

University of Southern California

Collaborator

Trials

956

Recruited

1,609,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Findings from Research

In a study of 178 patients with disseminated germ cell tumors, the addition of bleomycin to the chemotherapy regimen (PVP16B) significantly improved treatment outcomes compared to a regimen without bleomycin (PVP16), with a failure-free survival rate of 86% versus 69%.

Patients receiving the PVP16B regimen also had a higher overall survival rate of 95% compared to 86% in the PVP16 group, highlighting the importance of bleomycin in achieving better therapeutic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. Loehrer, PJ., Johnson, D., Elson, P., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial. [2022]

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

Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors. [2018]

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

Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983. [2022]

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

Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Treatment in germ cell tumours: state of the art. [2019]

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

Management of intermediate-prognosis germ-cell cancer: results of a phase I/II study of Taxol-BEP. [2019]

7. Australia pubmed.ncbi.nlm.nih.gov

Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy for intermediate to poor risk testicular germ cell tumors with unfavorable marker decline after initial two cycles chemotherapy: a report of three cases. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes. [2020]

9. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell tumors: a phase II study. [2015]

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

Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study. [2019]

11. Australia pubmed.ncbi.nlm.nih.gov

Complete response to paclitaxel, ifosfamide, and cisplatin therapy in a case of ovarian ependymoma. [2017]