Poor-risk Metastatic Germ Cell Tumours Research Articles

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for individuals aged 11-45 years with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS524 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard first-line chemotherapy for intermediate and poor-risk metastatic GCT. Accelerating standard chemotherapy regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. It aims to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2 stages. The primary endpoint for stage 1 (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival at 2 years (PFS2y). These sample sizes provide > 80% power with a two-sided type I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF 6mg D6 or filgrastim daily. Study assessments occur at 30 days after completing chemotherapy, 6 months from randomization, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of 24 August 2023, 274 participants have been recruited from 23 ANZ sites, 17 UK sites (led by Cambridge Clinical Trials Unit), and 150 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage 1 analysis of safety and activity (response rate) for the 1st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS5102 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for intermediate or poor risk metastatic GCT. Accelerating standard regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP will determine effects of accelerated versus standard BEP in this setting. This is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival at 2 years (PFS2y). These sample sizes provide > 80% power with a 2-sided type I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate- or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily (Figure 1). Study assessments occur at 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour and blood samples are collected for translational substudies. Progress - As of Jan 2023, 241 participants have been recruited from 22 ANZ sites, 16 UK sites (led by Cambridge Clinical Trials Unit), and 55 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage I analysis of safety and activity (response rate) for the 1st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate- and poor-risk metastatic germ cell tumours (GCTs).

TPS431 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for intermediate or poor risk metastatic GCT. Accelerating standard regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP will determine effects of accelerated versus standard BEP in this setting. This is a first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) was complete response (CR); and for stage 2 (n=500) is progression free survival at 2 years (PFS2y). These sample sizes provide >80% power with a two-sided type I error rate of 5% to detect an absolute improvement of 25% in the CR rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate-or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily. Study assessments occur at 30 days after completing chemotherapy, 6 months from randomization, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour and baseline blood samples are collected for translational substudies. Progress: As of Sept 2022, 226 participants have been recruited from 24 ANZ sites, 17 UK sites (led by Cambridge Clinical Trials Unit), and 149 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. Stage I analysis (n=150) showed sufficiently favorable results with no futility concerns, supporting ongoing trial recruitment. Clinical trial information: NCT02582697 .

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS390 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard first-line chemotherapy for metastatic GCT categorised as intermediate risk or poor risk. Acceleration of standard regimens by shortening the cycle length improved cure rates in other cancers. We aim to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomised, phase III trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) is complete response (CR); and for stage II (n=500) is progression free survival at 2 years (PFS2y). These sample sizes provide >80% power with a two-sided type error rate of 5% to detect an absolute improvement of 25% in the CR rate (stage II) and of 7% in the PFS2y (stage II). The target population is males and females aged 11 to 45 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomised (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily. Study assessments are 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies including assessment of favourable versus unfavourable rates of decline in the novel biomarker miR-371. As of 13 October 2020, 140 participants have been recruited from 25 ANZ sites, 14 UK sites (led by Cambridge Clinical Trials Unit), and 140 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. The stage I analysis is anticipated mid-2021. This international randomised trial of chemotherapy for intermediate and poor-risk metastatic GCT is the first to include adults and children of both sexes. ClinicalTrials.gov: NCT02582697 Clinical trial information: NCT02582697.

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS425 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a favourable response, and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in the favourable response rate and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 13 sites open in UK (led by Cambridge Clinical Trials Unit), 67 sites open in the USA (led by Children’s Oncology Group). As of September 2019, 98 patients have been recruited triggering the first formal interim analysis. Clinical trial information: NCT02582697.

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS539 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a complete response (CR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in achieving a CR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or Filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 11 sites open in UK (led by Cambridge Clinical Trials Unit), 19 sites open in the USA (led by Children’s Oncology Group). As of 23rd October 2018, 59 patients have been recruited. Clinical trial information: NCT02582697.

Current medical management of patients with poor-risk metastatic germ-cell tumors.

Despite the high cure rate of germ-cell tumors (GCTs), the 5-year survival rate for those patients with metastatic poor-risk GCT rarely exceeds 50%. The purpose of this review is to highlight past and recent discoveries in the treatment of patients with poor-risk GCT. Multiple clinical trials to optimize the management of poor-risk germ-cell cancer are ongoing. First-line phase II clinical trials of dose-dense multidrug and paclitaxel-based regimens such as accelerated bleomycin, etoposide, and cisplatin (BEP), dose-dense chemotherapy and paclitaxel, ifosfamide, and cisplatin (TIP) reported promising results. Positive phase III data are still lacking. Four cycles of BEP or Etoposide (VP16), ifosfamide, cisplatin (VIP) continue to be the standard of care in patients with poor-risk GCT. A significant disparity in patient outcome exists between high-volume and low-volume centers. Referral for centers of excellence should be considered in the management of poor-risk GCT.

Protocol for the P3BEP trial (ANZUP 1302): an international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours

BackgroundBleomycin, etoposide, and cisplatin (BEP) chemotherapy administered every 3 weeks for 4 cycles remains the standard first line treatment for patients with intermediate- and poor-risk metastatic germ cell tumours (GCTs). Administering standard chemotherapy 2-weekly rather than 3-weekly, so-called ‘accelerating chemotherapy’, has improved cure rates in other cancers. An Australian multicentre phase 2 trial demonstrated this regimen is feasible and tolerable with efficacy data that appears promising. The aim of this trial is to determine if accelerated BEP is superior to standard BEP as first line chemotherapy for adult and paediatric male and female participants with intermediate and poor risk metastatic GCTs.MethodsThis is an open label, randomised, stratified, 2-arm, international multicentre, 2 stage, phase 3 clinical trial. Participants are randomised 1:1 to receive accelerated BEP or standard BEP chemotherapy. Eligible male or female participants, aged between 11 and 45 years with intermediate or poor-risk metastatic GCTs for first line chemotherapy will be enrolled from Australia, the United Kingdom and the United States. Participants will have regular follow up for at least 5 years. The primary endpoint for stage 1 of the trial (n = 150) is complete response rate and for the entire trial (n = 500) is progression free survival. Secondary endpoints include response following treatment completion (by a protocol-specific response criteria), adverse events, health-related quality of life, treatment preference, delivered dose-intensity of chemotherapy (relative to standard BEP), overall survival and associations between biomarkers (to be specified) and their correlations with clinical outcomes.DiscussionThis is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and pediatric age groups open to both males and females. It is also the largest, current randomised trial for germ cell tumours in the world. Positive results for this affordable intervention could change the global standard of care for intermediate and poor risk germ cell tumours, improve cure rates, avoid the need for toxic and costly salvage treatment, and return young adults to long, healthy and productive lives.Trial registrationACTRN 12613000496718 on 3rd May 2013 and Clinicaltrials.gov NCT02582697 on 21st October 2015.

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS574 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in RR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days (D) 1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV (D 1, 8, 15 or D 2, 9, 16 of a 21 day cycle; D 1, 8 or D 2, 9 of a 14 day cycle); and peg G-CSF or Filgrastim; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 1/19 sites open in UK (led by Cambridge Clinical Trials Unit), 41 patients recruited by September 2017. International collaborations with USA (led by Children’s Oncology Group) and Ireland (led by Cancer Trials Ireland) confirmed with sites expected to open by late 2017 and more sites sought for stage 2. Clinical trial information: NCT02582697.

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS4592 Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Accelerating regimens by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and paediatric age groups open to both males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open-label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in RRs and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 yrs with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT:Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30-day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 27 sites open in ANZ, 34 patients recruited by February 2017. International collaborations with UK (led by Cambridge Clinical Trials Unit) and US (led by Childrens Oncology Group) confirmed with sites expected to open by early 2017, and more sites sought for stage 2. Funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and previously CINSW. ANZCTR: ACTRN12613000496718. Clinical trial information: NCT02582697.

Efficacy and tolerability of TIP (paclitaxel, ifosfamide and cisplatin) incorporated into induction chemotherapy for patients with intermediate- or poor-risk metastatic germ cell tumors.

The objective of this study was to analyze the clinical outcomes of TIP (paclitaxel, ifosfamide and cisplatin) incorporated into induction chemotherapy for patients with metastatic germ cell tumor (GCT) characterized by unfavorable clinical features. This study included 37 patients, who were categorized into intermediate- or poor-risk GCT according to the International Germ Cell Consensus Classification (IGCCC). All 37 patients received two cycles of bleomycin, etoposide and cisplatin (BEP) followed by several cycles of TIP. Following treatment with TIP, 25 patients achieved the normalization of serum tumor markers. In addition, surgical resection of the residual tumors following TIP was performed in 17 patients who were pathologically diagnosed with no viable cancer cells. At a median follow-up of 36 months, 31 patients were alive, including 27 with no evidence of disease, whereas the remaining six died of disease progression. The 5-year disease-free survival (DFS) and overall survival (OS) rates in these 37 patients were 72.9 and 85.3%, respectively. Despite the lack of a significant predictor of OS, univariate analysis identified the presence of a choriocarcinoma element and IGCCC as significant predictors of DFS, of which only the presence of a choriocarcinoma element appeared to be independently associated with DFS. In this series, treatment-related death did not occur, although 27 patients had at least one adverse event corresponding to grade 3 ≤. Collectively, it would be of worth to pursue the significance of the early incorporation of TIP into induction chemotherapy for patients with intermediate- or poor-risk metastatic GCT in the future.

872TiP - Anzup 1302: a Randomised Phase 3 Trial of Accelerated Versus Standard Bep Chemotherapy for Patients with Intermediate and Poor-Risk Metastatic Germ Cell Tumours (P3Bep)

ABSTRACT Background: Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). High-dose chemotherapy and more complex regimens (eg VIP, T-BEP) have failed to improve cure rates and are more toxic. Accelerating regimens of standard chemotherapy by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers where more complex or higher-dose regimens failed. Aim: To determine if accelerated BEP is superior to standard BEP as 1st line chemotherapy for intermediate and poor risk metastatic GCTs. Trial design: Open-label, randomised, stratified 2-arm multicentre, 2 stage, phase 3 clinical trial. The primary endpoint for stage I of the trial (n = 150) is complete response rate, and for the complete trial (n = 500) is progression-free survival (PFS). A sample size of 150 and 500 patients gives >80% power to detect a 20% improvement in response rates and 7% absolute improvement in 2yr PFS, respectively. Participants: Males aged 16-45years with intermediate or poor-risk metastatic GCTs for 1st line chemotherapy. Planned expansion to include children aged 11+ and females. Regimen: Participants are randomised 1:1 to “standard BEP” or “accelerated BEP”: Timing of BEP accelerated vs standard Week 1 2 3 4 5 6 7 8 9 10 11 12 Standard EP EP EP EP B B B B B B B B B B B B Accelerated EP EP EP EP B B B B B B B B B B B B E-Etoposide 100mg/m2 D1-5; P-Cisplatin25mg/m2 D1-5; B-Bleomycin 30000 IU weekly; Peg G-CSF 6mg s/c given on D6 post EP in both arms Assessments: Weekly during BEP. Initial response assessment at 30-day safety assessment. Final response assessment at 6 months from randomisation or after all post-chemotherapy intervention is completed. Follow-up 3-monthly for 2 years from randomisation, then 6-monthly to 5 years, then annually. Tissue and blood collection for translational substudies Current status: In start-up phase or open to recruitment at 25 sites in Australia & New Zealand. International trial groups invited to participate. Email: p3bep@ctc.usyd.edu.au Webstite: http://www.anzup.org.au/ Disclosure: All authors have declared no conflicts of interest.

874TiP - Anzup 1302 P3Bep Companion Translational Study: Prospective Collection of Whole Blood, Serum, Plasma and Tumour Tissue in a Randomized Trial of Chemotherapy for Metastatic Germ Cell Tumours (Gct)

ABSTRACT Background: The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a randomized trial of accelerated versus standard BEP chemotherapy for intermediate and poor risk metastatic GCTs. This translational substudy will prospectively collect blood and GCT tissue in a centralized biobank. Overall aim: To identify pharmacogenomic and molecular markers of treatment failure, toxicity and overall survival in metastatic GCTs. This could lead to the design of tailored treatments, for example incorporating a higher dose of or an alternative form of chemotherapy. Trial design: Specific objectives: 1. Consent ≤ 500 individuals in our trial for donation of blood and cancer tissue samples for future genomic analyses 2. Collect, process and freeze participant blood (50mL) as whole blood, plasma and serum pre-chemotherapy 3. Collect a representative formalin fixed paraffin embedded (FFPE) block of participant tumour tissue 4. Transport blood and cancer tissue samples to the Chris O'Brien Lifehouse cryostorage facility in Sydney, Australia 5. Establishment of a national biobank for testicular cancer Planned future objectives: Study association of progression (relapse or refractory disease), overall survival and toxicity (as surrogates for excess drug exposure) with genetic polymorphisms known to be involved in: - bleomycin metabolism: BLMH (bleomycin hydrolase gene) variant A1450G SNP - etoposide metabolism and transport: ABCB1 (3435T variant), CYP3A5 - candidate tumour-related markers including DNA methylation profiles of cancer-related genes Conclusions: The ultimate goal of this research is to facilitate a “personalised medicine” approach to the treatment of individuals with advanced germ cell tumours (GCT), with the ultimate goal of curing 100% of patients. We invite researchers with blood or tumour samples, and/or expertise in relevant laboratory techniques to collaborate in future analyses. Email: p3BEP@ctc.usyd.edu.au website: http://www.anzup.org.au Disclosure: All authors have declared no conflicts of interest.

High-dose chemotherapy in poor-risk germ cell tumours

Addition of high-dose chemotherapy (HDCT) to standard first-line treatment does not improve treatment response in patients with intermediate-risk or poor-risk metastatic germ cell tumours (GCT), according to results from a US multicentre randomised phase III study (J Clin Oncol 2007; 25: 247–56).

Better outcomes for patients with intermediate-risk and poor-risk metastatic germ-cell tumors

Better outcomes for patients with intermediate-risk and poor-risk metastatic germ-cell tumors

Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948)

New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9–79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7–66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5–91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6–93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.