TIP vs BEP Chemotherapy for Germ Cell Cancer

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Cytotoxic therapy, HAART

Disqualifiers: Prior chemotherapy, Concurrent malignancy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two chemotherapy treatments for individuals with intermediate- and poor-risk germ cell tumors (GCT). The study compares the current standard treatment, a combination of bleomycin, etoposide, and cisplatin (BEP), with an experimental mix of paclitaxel, ifosfamide, and cisplatin (TIP). Researchers aim to determine if the experimental combination is safer and more effective, as the current treatment does not work for everyone. Individuals recently diagnosed with GCT who have a testicular mass or elevated tumor markers might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in GCT treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the TIP treatment, which includes paclitaxel, ifosfamide, and cisplatin, is generally well-tolerated by patients, though it can cause some side effects. Previous studies identified myelosuppression, a drop in blood cell counts, as the most common side effect. Despite this, TIP has been used safely with proper monitoring and care.

The BEP treatment, consisting of bleomycin, etoposide, and cisplatin, is a standard treatment for germ cell tumors and has been in use for a long time. While effective, it can also cause side effects, such as lung problems related to bleomycin. Both treatments require careful management to ensure safety, but they have been successfully used in many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the TIP treatment for germ cell cancer because it combines paclitaxel, ifosfamide, and cisplatin to potentially offer a more effective approach than the standard BEP regimen. The inclusion of paclitaxel is a key differentiator; it disrupts cancer cell division by stabilizing microtubules, which might enhance the overall impact on tumor reduction. Additionally, the synergy between these drugs could lead to improved outcomes, making TIP a promising alternative to existing treatments like BEP, which typically relies on bleomycin.

What evidence suggests that this trial's treatments could be effective for germ cell tumors?

This trial will compare the TIP treatment plan with the BEP treatment plan for germ cell tumors. Studies have shown that the TIP treatment plan, which includes paclitaxel, ifosfamide, and cisplatin, is effective as a second option for treating germ cell tumors. In one study, 70% of patients experienced a significant decrease in tumor markers, demonstrating the treatment's effectiveness. Another study found that after five years, about 66% of patients were alive without cancer recurrence, and 69% were still alive overall. TIP is considered a strong choice for those whose cancer has returned after other treatments.

The BEP treatment plan, the standard approach in this trial, includes bleomycin, etoposide, and cisplatin. It has been successful for many patients with more challenging germ cell tumors. However, BEP does not work for everyone, prompting the exploration of new treatments like TIP in this trial. ^{1 6 7 8 9}

Who Is on the Research Team?

Darren R. Feldman

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4282876/

Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and ... Before TIP, 33 patients showed elevated tumor marker and 23 patients (70 %) achieved marker normalization with the chemotherapy. One of six (17 %) patients with ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.02542

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage ... Combination of Paclitaxel, Ifosfamide, and Cisplatin Is an Effective Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Tumors.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150303/

Paclitaxel, Ifosfamide & Cisplatin (TIP) as initial salvage ... With a median follow-up of nearly 9 years, the 5-year PFS and OS rates were 66% and 69%, respectively and importantly, similar outcomes were observed among ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02289-0/fulltext

707P Paclitaxel, ifosfamide and cisplatin (TIP) in patients ... The 1-year PFS and overall survival were 55% (39–72) and 76% (62–91), respectively. The favorable response rate (complete response (CR) + partial response with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666168321006716

Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor ... Paclitaxel, ifosfamide, and cisplatin (TIP) is considered one of standard salvage conventional dose regimens in GCTs with long-term survival from 36% to 63%. A ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2059702924012171

Efficacy and safety of high-dose chemotherapy as the first ... When used as the first salvage therapy, OS was superior with a 2-year OS rate of 74%. •. HD-CTX yielded a higher 79% ORR when administered as the initial ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01873326

Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin ... 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 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JOP.2016.011411

Salvage Therapy for Patients With Germ Cell Tumor Treatment with HDCT seemed to be more effective in most risk groups. Overall, 5-year survival was 53.2% for patients who received HDCT compared with 40.8% for ...

9. eviq.org.au eviq.org.au/medical-oncology/urogenital/testicular/316-testicular-germ-cell-recurrent-tip-paclitaxel

Testicular germ cell recurrent TIP (PACLitaxel iFOSFamide ... Estimated 2-year disease free survival is 47% (95% CI, 23-71%). Treatment combination was well tolerated and myelosupression was major toxicity.