Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

Learn more about:
Related Clinical Trial
A Phase II Trial Evaluating the Efficacy of Cabozantinib With Patients With Refractory GCTs Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults Symptom Management for YA Cancer Survivors A Study of miRNA 371 in Patients With Germ Cell Tumors Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors Aflac ST0901 CHOANOME – Sirolimus in Solid Tumors Study of Genistein in Pediatric Oncology Patients (UVA-Gen001) A Pilot RCT of the PRISM Intervention for AYAs With Cancer Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors Molecular-Guided Therapy for Childhood Cancer EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors Auto Transplant for High Risk or Relapsed Solid or CNS Tumors Busulfan in Treating Children and Adolescents With Refractory CNS Cancer CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven’t Responded to Therapy ABT-751 in Treating Young Patients With Refractory Solid Tumors Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Collecting and Storing Tissue From Young Patients With Cancer Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Everolimus in Refractory Testicular Germ Cell Cancer Studying Genes in Samples From Younger Patients With Ovarian or Testicular Sex Cord Stromal Tumors Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS) A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors First Line TIP in Poor Prognosis TGCTs. Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Electroacupuncture in Treating Delayed Nausea and Vomiting in Patients Receiving Chemotherapy For Newly Diagnosed Childhood Sarcoma, Neuroblastoma, Nasopharyngeal Cancer, Germ Cell Tumors, or Hodgkin Lymphoma Disulfiram and Cisplatin in Refractory TGCTs. Role of Axumin PET Scan in Germ Cell Tumor Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors Study Evaluating the Impact of Short Message Service on Compliance With Surveillance of Patients With Germ-cell Tumors Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors Etoposide, Carboplatin, and Bleomycin in Treating Young Patients Undergoing Surgery For Malignant Germ Cell Tumors Studying Biomarkers in Samples From Younger Patients With Malignant Germ Cell Tumor Progression Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors Proton Beam Radiation Therapy for Central Nervous System (CNS) Germ Cell Tumors Germ Cell Tumor and Testicular Tumor DNA Registry A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors

Brief Title

Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

Official Title

Phase 3 Accelerated BEP: A Randomised Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

Brief Summary

      The purpose of this study is to determine whether accelerated BEP chemotherapy is more
      effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic
      germ cell tumours.
    

Detailed Description

      Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line
      chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates
      are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk
      disease. Previous strategies to improve first-line chemotherapy have failed to improve cure
      rates and were more toxic than BEP. New strategies are needed for patients with intermediate
      and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead
      of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group
      (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP. The aim of this
      study is to determine if accelerated BEP is superior to standard BEP as first-line
      chemotherapy for intermediate and poor risk metastatic GCTs.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Progression-free survival (disease progression or death)

Secondary Outcome

 Initial response assessment

Condition

Germ Cell Tumor

Intervention

Bleomycin (active name: Bleomycin Sulfate)

Study Arms / Comparison Groups

 Standard Arm - Standard BEP
Description:  Participants 16 years or older will receive 4 cycles of Standard BEP as follows:
Bleomycin 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Pegylated G-CSF 6 mg SCI on day 6
Patients < 16 years old and weighs ≥ 45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Pegylated G-CSF 6 mg SCI on day 6
Patients <16 years old and weighs < 45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Filgrastim 10mcg/kg/day on day 6, until post-nadir Absolute Neutrophil Count ≥1 x10^9/ L
The dose of bleomycin is decided by the treating physician and based on the patient's Body Surface Area.
Each cycle is 3 weeks (21 days).
The planned total duration of treatment is 12 weeks.

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

500

Start Date

February 2014

Completion Date

July 2023

Primary Completion Date

February 2022

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 11 years and ≤ 45 years on the date of randomisation

          2. Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma);
             or Exceptionally raised tumour markers (AFP ≥ 1000ng/mL and/or HCG ≥ 5000 IU/L)
             without histologic or cytologic confirmation in the rare case where pattern of
             metastases consistent with GCT, high tumour burden, and a need to start therapy
             urgently

          3. Primary arising in testis, ovary, retro-peritoneum, or mediastinum

          4. Metastatic disease or non-testicular primary

          5. Intermediate or poor prognosis as defined by IGCCC classification3 (modified with
             different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian
             primaries). (See protocol for more information).

          6. Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L

          7. Adequate liver function where bilirubin must be ≤1.5 x ULN, except participants with
             Gilbert's Syndrome where bilirubin must be ≤2.0 x ULN; ALT and AST must be ≤2.5 x ULN,
             except if the elevations are due to hepatic metastases, in which case ALT and AST must
             be ≤ 5 x ULN

          8. Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to
             the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in
             which case GFR should be formally measured, eg. with EDTA scan

          9. ECOG Performance Status of 0, 1, 2, or 3

         10. Study treatment both planned and able to start within 14 days of randomisation.

         11. Willing and able to comply with all study requirements, including treatment, timing
             and nature of required assessments

         12. Able to provide signed, written informed consent

        Exclusion Criteria:

          1. Other primary malignancy (EXCEPT adequately treated non-melanomatous carcinoma of the
             skin, germ cell tumour, or other malignancy treated at least 5 years previously with
             no evidence of recurrence)

          2. Previous chemotherapy or radiotherapy, except if patient has pure seminoma relapsing
             after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent
             carboplatin or if patient has non-seminoma and poor prognosis by IGCCC criteria in the
             rare case where low-dose induction chemotherapy is given prior to registration because
             patient is not fit enough to receive protocol chemotherapy (eg. organ failure, vena
             cava obstruction, overwhelming burden of disease). In these instances acceptable
             regimens include cisplatin 20 mg/m^2 days 1-2 and etoposide 100 mg/m^2 days 1-2;
             carboplatin AUC 3 days 1-2 and etoposide 100 mg/m^2 days 1-2; or baby-BOP. Patients
             must meet all other inclusion and exclusion criteria at the time of registration.

             Additionally participants who need to start therapy urgently prior to completing
             study-specific baseline investigations may commence study chemotherapy prior to
             registration and randomisation. Such patients must be discussed with the coordinating
             centre prior to registration, and must be registered within 10 days of commencing
             study chemotherapy.

          3. Significant cardiac disease resulting in inability to tolerate IV fluid hydration for
             cisplatin

          4. Significant co-morbid respiratory disease that contraindicates the use of bleomycin

          5. Peripheral neuropathy ≥ grade 2 or clinically significant sensorineural hearing loss
             or tinnitus

          6. Concurrent illness, including severe infection that may jeopardize the ability of the
             participant to undergo the procedures outlined in this protocol with reasonable safety

          7. Inadequate contraception. Men must use 2 effective methods of contraception, including
             use of a condom, during chemotherapy and for a year after completing chemotherapy.

          8. Known allergy or hypersensitivity to any of the study drugs

          9. Presence of any psychological, familial, sociological or geographical condition that
             in the opinion of the investigator would hamper compliance with the study protocol and
             follow-up schedule, including alcohol dependence or drug abuse

        The above inclusion and exclusion criteria will apply to stage 1 (n=150) and stage 2 (n=500
        including stage 1) of the study. All sites will participate in both stages of the study
        with the exception of the Children's Oncology Group who will be participate in stage 1
        only.
      

Gender

All

Ages

11 Years - 45 Years

Accepts Healthy Volunteers

No

Contacts

Peter Grimison, +6195625000, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT02582697

Organization ID

ANZUP1302

Secondary IDs

ACTRN12613000496718

Responsible Party

Sponsor

Study Sponsor

University of Sydney

Collaborators

 Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Study Sponsor

Peter Grimison, Study Chair, Chris O'Brien Lifehouse


Verification Date

November 2020