Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) Versus Carboplatin in Stage I Seminomatous Testicular Cancer

Brief Title

Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) Versus Carboplatin in Stage I Seminomatous Testicular Cancer

Official Title

A Randomized Phase III Study Comparing One Course of Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) and One Course of Carboplatin AUC7 in Clinical Stage I Seminomatous Testicular Cancer

Brief Summary

      One course of adjuvant carboplatin AUC7 is considered internationally to be a standard
      treatment option in clinical stage I seminoma, regardless of risk factors. Treatment is based
      on a large, randomized phase III study comparing adjuvant carboplatin with adjuvant
      radiotherapy. This study was done without registering data on possible risk factor for
      relapse. The relapse rate following carboplatin was in this study estimated to be 5.3 %. Data
      from a prospective, risk-adapted Spanish study showed that patients without risk factors had
      a very low risk of relapse, even without adjuvant treatment. This result is also confirmed by
      a recent analysis of SWENOTECA VII data, showing that this group of patients has a risk of
      relapse of less than 5 % without adjuvant treatment.

      Combined data from SWENOTECA V and VII studies indicate a high risk of relapse in patients
      with one or two risk factors (tumor 4 cm, stromal invasion of rete testis) treated with one
      course of adjuvant carboplatin. The relapse rate in this group of patients was 9.4 %,
      indicating a very modest effect of one course of adjuvant carboplatin. If adjuvant
      chemotherapy is the preferred treatment strategy, more potent chemotherapy regimens should be
      explored in this patient group. The results from SWENOTECA III/VI studies with one course of
      cisplatin-based adjuvant chemotherapy in clinical stage I nonseminoma, show a very low rate
      of relapse. As seminoma is even more chemosensitive than nonseminoma the relapse rate
      following one course of adjuvant BEP is expected to be very low, close to 1 %.

      The overall aim is to investigate whether one course of adjuvant BEP have a lower relapse
      rate than one course of adjuvant carboplatin AUC7. In addition, it will be investigated if
      there is a difference in health related quality of life as well as acute and long-term
      toxicities from treatment.
    

Detailed Description

      Short term overall survival is, regardless of treatment allocation, expected to be very close
      to 100 %. The primary outcome is relapse rate. The power of the study depends on the number
      of observed relapses. If the relapse rate in the adjuvant carboplatin group, the reference
      group, is lower than the anticipated 9 %, we need to include more patients to the study.
      Based on all previous published material on adjuvant treatment in clinical stage I seminoma
      it is not possible to precisely estimate the correct relapse rate until the median follow-up
      is four years. Consequently, we will estimate the relapse rate in the reference group close
      to the end of accrual. If the estimated relapse rate, and thus the number of relapses, is
      lower than the anticipated we will increase the sample size to make sure that the study meets
      the minimum required number of relapses in the reference group. A possible inclusion of more
      study participants does not compromise the Type I error rate of the study.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Relapse rate


Condition

Testicular Neoplasms

Intervention

Bleomycin Etoposide and Cisplatin

Study Arms / Comparison Groups

 Bleomycin-Etoposide-Cisplatin
Description:  One course of adjuvant BEP.

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

348

Start Date

April 8, 2015

Completion Date

December 2020

Primary Completion Date

December 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Histological diagnosis of unilateral seminoma testicular cancer, evaluating both size
             of tumor and invasion of the rete testis

          -  Clinical stage I

          -  Tumor size over 4 cm and/or stromal invasion of the rete testis by tumor cells

          -  Normal value of alpha-fetoprotein (AFP) before orchiectomy. A stable, slightly
             elevated AFP as a normal value may be permitted.

          -  Age ≥ 18 years and < 60 years

          -  Adequate organ function defined as:

        Serum aspartate transaminase (ALT) ≤ 1.5 x upper limit of normal (ULN). Total serum
        bilirubin ≤ 1.5 x ULN Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L
        Creatinine clearance > 50 ml/min (eGFR) All fertile patients should use safe contraception
        Written informed consent

        Exclusion Criteria:

          -  Signs of metastatic disease evaluated by CT thorax, abdomen and pelvis. Patients in
             need of restaging (see SWENOTECA IX) should not be included

          -  Prior diagnosis of testicular cancer

          -  Chronic pulmonary disorders giving a high risk of bleomycin induced toxicity (for
             example chronic obstructive pulmonary disease or lung fibrosis)

          -  Cancer other than seminoma testicular cancer

          -  Known hypersensitivity or contraindications for the study drugs

          -  Serious concomitant systemic disorders (for example active infection, unstable
             cardiovascular disease) that in the opinion of the investigator would compromise the
             patient's ability to complete the study or interfere with the evaluation of the
             efficacy and safety of the study treatment

          -  Medical, social, psychological conditions that could prevent adequate information and
             follow-up
      

Gender

Male

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Olof Ståhl, Md PhD, +47 72826166, [email protected]

Location Countries

Norway

Location Countries

Norway

Administrative Informations


NCT ID

NCT02341989

Organization ID

2014/2012

Secondary IDs

2014-004075-23

Responsible Party

Sponsor

Study Sponsor

St. Olavs Hospital

Collaborators

 Skane University Hospital

Study Sponsor

Olof Ståhl, Md PhD, Principal Investigator, Skane University Hospital


Verification Date

November 2019