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

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Brief Title

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

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

Brief 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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

favorable best response rate

Secondary Outcome

 overall best response

Condition

Germ Cell Tumors

Intervention

Paclitaxel

Study Arms / Comparison Groups

 Paclitaxel, Ifosfamide and Cisplatin (TIP)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

92

Start Date

June 2013

Completion Date

June 2021

Primary Completion Date

June 2021

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Darren Feldman, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01873326

Organization ID

13-074


Responsible Party

Sponsor

Study Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

 University of Southern California

Study Sponsor

Darren Feldman, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center


Verification Date

July 2020