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Trial registered on ANZCTR


Registration number
ACTRN12607000294459
Ethics application status
Approved
Date submitted
25/05/2007
Date registered
4/06/2007
Date last updated
14/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
“Accelerated BEP”
A feasibility study of accelerated BEP as first line chemotherapy for advanced germ cell tumours
Scientific title
“Accelerated BEP - A feasibility study on the safety of accelerated Bleomycin, Etoposide, Cisplatin, and Pegylated G-CSF (BEP) as first line chemotherapy for advanced germ cell tumours”
Secondary ID [1] 259826 0
None
Universal Trial Number (UTN)
Trial acronym
Accelerated BEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
First Line Chemotherapy for Advanced Germ Cell Tumours 1836 0
Condition category
Condition code
Cancer 1929 1929 0 0
Ovarian and primary peritoneal
Cancer 1930 1930 0 0
Testicular

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Accelerated BEP chemotherapy, consisting of:
- Bleomycin 30000 international units intravenous (IV) days 1 and 8
- Etoposide 100mg/m2 IV days 1, 2, 3, 4, 5
- Cisplatin 20mg/m2 IV days 1, 2, 3, 4, 5
with pegylated G-CSF (pegfilgastrim, Neulasta) 6mg SCI administered on day 6

For patients with intermediate or poor risk disease, treatment is repeated every 2 weeks for 4 cycles. An additional 4 weeks of Bleomycin will be administered if lung function tests allow to a maximum of 12 doses. Total duration – 12 weeks

For patients with good risk disease, treatment is repeated every 2 weeks for 3 cycles. An additional 3 weeks of Bleomycin will be administered if lung function tests allow to a maximum of 9 doses. Total duration – 9 weeks
Intervention code [1] 1783 0
Treatment: Drugs
Comparator / control treatment
N/A Single Arm Trial
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2743 0
The primary endpoint of the study is the feasibility of the regimen, defined as the proportion of patients eligible to start their 4th cycle of BEP within 50 days of their first dose of chemotherapy.
Success will require completion of 3 cycles of BEP followed by adequate recovery of full blood count from the 3rd cycle of BEP (absolute neutrophil count = 1.0 x 109/L, platelet count = 100 x 109/L) prior to day 50
Both intermediate-poor risk patients (who will proceed to a 4th cycle of BEP), and good risk patients (who will have completed their etoposide and cisplatin) will be included in this endpoint
Patients completing treatment with non-protocol specified modifications will not be counted as successes.
Timepoint [1] 2743 0
At day 50 after first dose of chemotherapy.
Secondary outcome [1] 4630 0
1. The proportion of patients experiencing grade 3 and 4 toxicities, as defined by the Common Toxicity Criteria v3.0 of the National Cancer Institute (NCI CTC V3.0); especially febrile neutropaenia, infection, nephrotoxicity, neurotoxicity, ototoxicity, pulmonary toxicity and secondary haematological malignancy.
Timepoint [1] 4630 0
Assessed prior to each cycle of BEP, prior to additional bleomycin, and after surgery or 30 days after last protocol chemotherapy.
Secondary outcome [2] 4631 0
2. The proportion of patients with continuous complete remission (CCR) at 12 months. CCR requires disease status of CR or no evidence of disease (NED) for non-seminomas; and CR, NED or residual, marker-negative radiologic abnormalities for pure seminomas.
Timepoint [2] 4631 0
Assessed at 12 months post-protocol completion.
Secondary outcome [3] 4632 0
3. The relative dose intensity of treatment compared with standard BEP
- The relative dose intensity is calculated by dividing the actual mean dose (per week) of drug delivered in the study, by the mean dose (per week) of drug delivered in a standard BEP regimen.
- The actual mean dose of drug delivered for both cisplatin and etoposide will be calculated by dividing the total dose administered (per meter squared) by the number of weeks over which the drugs were administered.
The planned mean dose for cisplatin is 50mg/m2/week (300mg/m2 over 6 weeks or 400mg/m2 over 8 weeks).
The planned mean dose for etoposide is 250mg/m2/week (1500mg/m2 over 6 weeks or 2000mg/m2 over 8 weeks).
- The mean dose of standard BEP is as follows:
for cisplatin: 33.3 mg/m2/week (300mg/m2 over 9 weeks or 400mg/m2 over 12 weeks)
for etoposide: 166.6 mg/m2/week (1500mg/m2 over 9 weeks or 2000mg/m2 over 12 weeks)
- The planned relative dose intensity is therefore 1.5
Timepoint [3] 4632 0
Assessed at the end of treatment.
Secondary outcome [4] 4633 0
4. The proportion of patients with maximum reductions from baseline in diffusing capacity of carbon monoxide (DLCO) adjusted for haemoglobin and/or vital capacity of:
(i) <15% (ii) 15% - 25% (iii) >25%
Timepoint [4] 4633 0
Assessed prior to the commencement of each cycle of accelerated chemotherapy, at end of treatment and prior to additional bleomycin treatment.
Secondary outcome [5] 4634 0
5. The proportion of patients with significant changes in patient-rated neurotoxicity (deterioration of = 5 points on a 40-point scale), as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire (FACT/GOG-Ntx) (Calhoun, Welshman et al. 2003)
Timepoint [5] 4634 0
Patient rated neurotoxicity assessed at each treatment cycle and at the end of treatment.

Eligibility
Key inclusion criteria
Subjects with histologically proven germ cell tumours (GCT), non-seminoma germ cell tumour (NSGCT) or seminoma arising in testis, retro-peritoneum, mediastinum or ovary- Exceptionally raised tumour markers (Alpha-fetoprotein (AFP) = 1000ng/mL and/or ß-Human chronic gonadotropin (HCG) = 5000 IU/L) are acceptable without histologic confirmation only in male patients with appropriate clinical picture- Relapses on surveillance are also acceptable2. Advanced stage with radiologically measurable disease according to Response Evaluation Criteria in Sold Tumors (RECIST).3. Intermediate risk, poor risk, or selected good risk patients (as defined by modified International Germ Cell Consensus Classification)- Patients must fulfil all of the following criteria in a particular category:- NSGCT – intermediate risk Testis, retro-peritoneal or ovarian primary, and No liver, bone, brain or other non-pulmonary visceral metastases, and Intermediate markers – any of AFP =1,000 and =10,000 µg/L B-HCG = 5,000 and = 50,000 iU/L Lactate dehydrogenase (LDH) = 1.5 x upper limit of normal and = 10 * N upper limit of normal- NSGCT – poor risk Mediastinal primary, or Liver, bone, brain or other non-pulmonary visceral metastases, or Poor markers – any of AFP > 10,000 µg/L B-HCG > 50,000 iU/L LDH > 10 x upper limit of normal- Seminoma - intermediate prognosis Any primary site, and Liver, bone, brain or other non-pulmonary visceral metastases must be present Normal Alpha-fetoprotein (AFP). Any B-HCG. Any LDH- Selected patients with good risk features will also be eligible at investigator’s discretion. These patients must have radiologically measurable disease according to RECIST. Patients with elevated serum tumour markers as the only evidence of disease are ineligible.- NSGCT – good risk Testis/retroperitoneal primary and No non-pulmonary visceral metastases and Good markers – all of AFP <1000 µg/L and B-HCG < 5,000 U/L and LDH < 1.5 x upper limit of normal- Seminoma – good risk Any primary site, and No non-pulmonary visceral metastases and Markers – all of Normal AFP and Any B-HCG Any LDH 4. Adequate bone marrow function (Absolute neutrophil count (ANC) = 1.0 x 109/L, platelet count =100 x 109/L)5. Adequate hepatic function (Bilirubin must be = 1.5 x upper limit of normal range, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) must be = 2.5 x upper limit of normal (ULN) except if the elevations are due to metastatic disease6. Adequate renal function (glomerular filtration rate (GFR) estimated with the Cockcroft-Gault formula = 60 ml/min).7. Able to commence treatment within 7 days of enrolment8. Able to comply with all treatment, assessments and follow-up9. Written, informed consent
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
2. Previous malignancy (other than germ cell malignancy, basal cell carcinoma or non-invasive squamous cell carcinoma of skin)3. Previous chemotherapy or radiotherapy, except patients with pure seminoma relapsing after radiotherapy.4. Uncontrolled medical condition including significant cardiac disease resulting in inability to tolerate intravenous fluid hydration for cisplatin5. Peripheral neuropathy = grade 2 or clinically significant sensori-neural hearing loss or tinnitus (audiometric abnormalities without corresponding clinical deafness are not grounds for exclusion)6. Medical or psychiatric condition disorder that compromises the patient’s ability to give informed consent7. Known hypersensitivity to cisplatin, etoposide, bleomycin or pegfilgrastrim (Neulasta)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A paper based registration system is used.
Allocation concealment is not applicable to this trial. It is a single arm open-label trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A - This is a single arm open-label registration trial. There is no randomisation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Primary endpoint is feasibility of the regimen
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/07/2007
Actual
28/02/2008
Date of last participant enrolment
Anticipated
30/11/2010
Actual
30/11/2010
Date of last data collection
Anticipated
Actual
Sample size
Target
45
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA
Recruitment postcode(s) [1] 1592 0
3690, 2137, 5042, 2750, 3001, 4102, 2031, 5000, 3052, 2050, 3065, 4066, 2145, 3011, 4066

Funding & Sponsors
Funding source category [1] 2074 0
Other Collaborative groups
Name [1] 2074 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Country [1] 2074 0
Australia
Funding source category [2] 270000 0
Charities/Societies/Foundations
Name [2] 270000 0
Cancer Council NSW, VIC, SA and QLD.
Country [2] 270000 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
NHMRC Clinical Trials Centre
Level 6, Medical Foundations Building
92-94 Parramatta Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 1879 0
Other Collaborative groups
Name [1] 1879 0
Australian New Zealand Gynaecological Oncology Group (ANZGOG)
Address [1] 1879 0
NHMRC Clinical Trials Centre Locked Bag 77 Camperdown NSW 1450 Australia
Country [1] 1879 0
Australia
Other collaborator category [1] 252283 0
Other Collaborative groups
Name [1] 252283 0
Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Address [1] 252283 0
ANZGOG
Level 4, Medical Foundation Building
92-94 Parramatta Road
CAMPERDOWN NSW 2050
Country [1] 252283 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3849 0
Princess Alexandra Hospital
Ethics committee address [1] 3849 0
Ethics committee country [1] 3849 0
Australia
Date submitted for ethics approval [1] 3849 0
Approval date [1] 3849 0
Ethics approval number [1] 3849 0
Ethics committee name [2] 3850 0
Westmead Hospital
Ethics committee address [2] 3850 0
Ethics committee country [2] 3850 0
Australia
Date submitted for ethics approval [2] 3850 0
Approval date [2] 3850 0
Ethics approval number [2] 3850 0
Ethics committee name [3] 3851 0
Border Medical Oncology
Ethics committee address [3] 3851 0
Ethics committee country [3] 3851 0
Australia
Date submitted for ethics approval [3] 3851 0
Approval date [3] 3851 0
Ethics approval number [3] 3851 0
Ethics committee name [4] 3852 0
Flinders Medical Centre
Ethics committee address [4] 3852 0
Ethics committee country [4] 3852 0
Australia
Date submitted for ethics approval [4] 3852 0
Approval date [4] 3852 0
Ethics approval number [4] 3852 0
Ethics committee name [5] 3853 0
Royal Adelaide Hospital
Ethics committee address [5] 3853 0
Ethics committee country [5] 3853 0
Australia
Date submitted for ethics approval [5] 3853 0
Approval date [5] 3853 0
Ethics approval number [5] 3853 0
Ethics committee name [6] 3854 0
Peter MacCallum Cancer Centre
Ethics committee address [6] 3854 0
Ethics committee country [6] 3854 0
Australia
Date submitted for ethics approval [6] 3854 0
Approval date [6] 3854 0
Ethics approval number [6] 3854 0
Ethics committee name [7] 3855 0
Royal Melbourne Hospital
Ethics committee address [7] 3855 0
Ethics committee country [7] 3855 0
Australia
Date submitted for ethics approval [7] 3855 0
Approval date [7] 3855 0
Ethics approval number [7] 3855 0
Ethics committee name [8] 3856 0
Western Hospital
Ethics committee address [8] 3856 0
Ethics committee country [8] 3856 0
Australia
Date submitted for ethics approval [8] 3856 0
Approval date [8] 3856 0
Ethics approval number [8] 3856 0
Ethics committee name [9] 3857 0
St Vincents Hospital
Ethics committee address [9] 3857 0
Ethics committee country [9] 3857 0
Australia
Date submitted for ethics approval [9] 3857 0
Approval date [9] 3857 0
Ethics approval number [9] 3857 0
Ethics committee name [10] 3858 0
Human Research Ethics Committee at the University of Sydney
Ethics committee address [10] 3858 0
Ethics committee country [10] 3858 0
Australia
Date submitted for ethics approval [10] 3858 0
Approval date [10] 3858 0
22/03/2007
Ethics approval number [10] 3858 0
02/2007/9848
Ethics committee name [11] 271960 0
Cancer Institute NSW Clinical Human Research Ethics Committee
Ethics committee address [11] 271960 0
Ethics committee country [11] 271960 0
Australia
Date submitted for ethics approval [11] 271960 0
Approval date [11] 271960 0
04/10/2007
Ethics approval number [11] 271960 0
Ethics committee name [12] 294031 0
Sydney Local Health District Royal Prince Alfred Hospital HREC
Ethics committee address [12] 294031 0
Ethics committee country [12] 294031 0
Australia
Date submitted for ethics approval [12] 294031 0
07/10/2013
Approval date [12] 294031 0
21/02/2014
Ethics approval number [12] 294031 0
HREC/13/RPAH/493

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27886 0
Dr Peter Grimison
Address 27886 0
NHMRC Clinical Trials Centre
University of Sydney
Chris O'Brien Lifehouse Level 6, 119-142 Missenden Road
Camperdown NSW 2050
Country 27886 0
Australia
Phone 27886 0
+61 2 9562 5000
Fax 27886 0
Email 27886 0
[email protected]
Contact person for public queries
Name 10972 0
Accelerated BEP Trial Coordinator
Address 10972 0
NHMRC Clinical Trials Centre
Level 6, Medical Foundations Building
92-94 Parramatta Road Camperdown NSW 2050
Country 10972 0
Australia
Phone 10972 0
(02) 9562 5000
Fax 10972 0
(02) 9562 5094
Email 10972 0
[email protected]
Contact person for scientific queries
Name 1900 0
Accelerated BEP Trial Coordinator
Address 1900 0
NHMRC Clinical Trials Centre
Level 6, Medical Foundations Building
92-94 Parramatta Road Camperdown NSW 2050
Country 1900 0
Australia
Phone 1900 0
(02) 9562 5000
Fax 1900 0
(02) 9562 5094
Email 1900 0
[email protected]

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