Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors

Germ Cell Tumors Clinical Trial

Official title:

Randomized Phase II Trial of Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-Risk Germ Cell Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01873326
• Other study ID #: 13-074
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: June 2024

Study information

• Verified date: June 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 92
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients = 18 years of age.

• Patients with newly diagnosed GCT

• Pathology confirmation of GCT histology at MSKCC or a collaborating treating institution. In exceptional circumstances, patients without pathological diagnosis may be included in the study following discussion with the national principal investigator, Dr. Feldman,(or national Co-PI or MSKCC Co-PI if the national PI is unavailable) if they meet the one of the following criteria:

• Patients with a testicular mass (detected clinically and/or by ultrasound), and/or mediastinal or retroperitoneal lymphadenopathy or pineal tumor AND elevated serum tumor markers (HCG and/or AFP). Patients with elevated LDH only will not be included without pathological confirmation of GCT since LDH is a nonspecific marker for GCT and could potentially be elevated in other malignancies such as lymphomas.

This is because patients may present with a clinical scenario consistent with GCT (elevated serum tumor markers, testicular mass and retroperitoneal lymphadenopathy) with a concurrent life-threatening oncologic emergency that require immediate treatment. In this case, initial treatment without biopsy confirmation is usually recommended and tissue confirmation may be obtained after initiating therapy.

• Patients must have measurable or evaluable disease.

• Patients must be classified as having intermediate or poor-risk germ cell tumor, as follows:

• Intermediate-risk (Modified*) a) Testis or retroperitoneal primary NSGCT with lymph node and/or lung metastasis but without non-pulmonary visceral metastasis AND any of the following pretreatment serum tumor marker (STM) values: i. Lactate dehydrogenase (LDH) from 3 to <10 x ULN (*This differs from the original IGCCCG criteria which includes patients with LDH from 1.5 to 10 x ULN).

ii. Serum human chorionic gonadotrophin (HCG) from 5,000 to < 50,000 MIU/mL iii. Serum alpha-fetoprotein (AFP) from 1,000 to <10,000 ng/mL b) Seminoma histology regardless the primary site or serum tumor markers with any non-pulmonary visceral metastasis (liver, bone, brain, etc).

• Poor-risk (any of the following):

1. Testis or retroperitoneal NSGCT primary with non-pulmonary visceral metastasis (liver, bone, brain, etc) regardless the STM values.

2. Mediastinal NSGCT primary site of disease regardless the presence/absence of visceral metastasis or STM values.

3. Testis or retroperitoneal NSGCT primary without non-pulmonary visceral metastasis but with poor-risk STM values:

• i. LDH = 10 x ULN

• ii. HCG = 50,000 MIU/mL

• iii. AFP = 10,000 ng/mL

• Patients who received prior radiation therapy (RT) for treatment of germ cell tumor are eligible for this study as long as there is evidence of progressive disease determined by tumor markers or other sites of metastases outside of the radiated site. Radiation must be completed prior to starting chemotherapy with the exception of brain metastases where chemotherapy and radiation can be given concurrently. Toxicity from radiation must have recovered to grade 1 or less prior to initiating chemotherapy.

• Patients must have recovered from prior surgery based on treating physician's discretion.

• Patients of reproductive potential must agree to use effective contraception during the period of therapy

• Signed informed consent.

• Diffusion lung capacity for carbon monoxide (DLCO) adjusted for hemoglobin =60% predicted, except if related to high volume metastatic GCT to the lungs in which case there is no minimum DLCO requirement. In some cases, patients may not be able to undergo PFT testing due to the severity of their presentation. such as those with high volume lung metastases or tumor-related pain (from large mediastinal masses, pleural disease, etc.) limiting their ability to complete PFTs. Even when PFTs can be completed in these cases, patients will still be eligible if the low DLCO can be attributed directly to the patient's disease (e.g., large mediastinal mass) rather than intrinsic lung disease. Since there is no minimum DLCO for these patients, under these extraordinary circumstances, this will be allowed. Most patients in this situation will be expected to receive disease-stabilizing chemotherapy. An unadjusted DLCO may be used in place of the DLCO adjusted for hemoglobin in certain situations as per institutional policy. For example, MSKCC policy is to not adjust the DLCO for hemoglobin when the hemoglobin is = 14.6 g/dL for males and = 13.4 g/dL for females. In these cases, the unadjusted DLCO must be >60% predicted.

• Laboratory criteria for protocol entry (obtained = 14 days before initiation of therapy):

• WBC = 3000/UL and Platelet count = 100,000/UL

• Serum creatinine = 1.5 mg/dL or estimated GFR (by Cockcroft-Gault) =50mL/min or 12 or 24 hour urine creatinine clearance = 50 mL/min, unless renal insufficiency is due to tumoral ureteral obstruction in which case eligibility will be determined by national the principal investigator (or national co-PI or MSKCC co-PI if the national PI is unavailable) with notification of the MSKCC IRB.

• AST/ALT = 3 x ULN and total bilirubin = 2.0 x ULN. In the setting of metastatic disease to the liver, AST/ALT may be =5x ULN and total bilirubin =2.5 x ULN. If a patient is known or suspected to have Gilbert's disease, total bilirubin up to =2.5 x ULN is allowed.

Exclusion Criteria:

• Any prior chemotherapy. The only exception will be patients with a history of stage I seminoma treated with adjuvant carboplatin for 1 or 2 cycles.

• Concurrent treatment with any cytotoxic therapy.

• Known concurrent malignancy (except for non-melanoma skin cancer).

• Patients known to be HIV positive and receiving HAART.

• Presence of an active infection. Patients with fever assessed to be "tumor fever" but without active evidence of infection (e.g. blood cultures are negative) are eligible. In addition, patients who have an infection but without evidence of fever for 48 hours on antibiotics will be eligible.

• Inability to comply with the treatment protocol or to undergo prespecified follow-up tests for safety or effectiveness.

• Pregnant patients are ineligible

Related Conditions & MeSH terms

• Germ Cell Tumors
• Neoplasms, Germ Cell and Embryonal

Intervention

Drug:
• Paclitaxel

• Ifosfamide

• Cisplatin

• Mesna

• Bleomycin

• Etoposide

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	Basking Ridge	New Jersey
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	University of Southern California	Los Angeles	California
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Follow-up Only)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University Medical Center	Stanford	California
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (8)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Mayo Clinic, Stanford University, University of Chicago, University of North Carolina, University of Pittsburgh, University of Southern California, University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	favorable best response rate	Favorable best response is defined as complete response or partial response with negative tumor markers. Patients will be considered evaluable for the primary endpoint of favorable response within the first 6 months if they complete at least 3 cycles of study treatment (without switch to an alternative chemotherapy regimen) and achieve a confirmed partial response with negative markers or confirmed complete response (considered as favorable responses). Patients will also be considered evaluable for the primary endpoint if they develop disease progression during the treatment portion of the study regardless of how many cycles of chemotherapy they received or if they achieve an incomplete response after completion of study treatment (considered as not having a favorable response)."	6 months
Secondary	overall best response	Overall best response refers to the best response achieved by a patient to either TIP or BEP over the course of the entire study.	3 years
Secondary	progression-free survival (PFS)	Progression-free survival (PFS) will be calculated from the date of treatment start until disease progression, death, or last followup, whichever comes first. The following are included as PFS events: incomplete response (IR), relapse or disease progression, and death.	3 years
Secondary	overall survival (OS)	Overall survival will be calculated from the date of treatment start until death, regardless of the cause.	3 years
Secondary	toxicity	Toxicity will be assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade of each toxicity will be recorded for each patient over the course of treatment (all cycles). Special emphasis will be placed on comparisons of the frequency of Grade 3/4 toxicities between the TIP and BEP arms.	30 days after completion of the last cycle of chemotherapy.

External Links

•   Memorial Sloan Kettering Cancer Center