reduced intensity radio-chemotherapy for stage iia/b seminoma

Conditions: Seminoma; Testicular Cancer

Summary: the trial investigates a stage-adapted (stage iia or iib) de-escalation of the standard treatments in the context of a multimodality treatment with chemo- and radiotherapy in seminoma patients. the goal is to safely de-escalate treatment while maintaining/enhancing efficacy, which is not a standard practice yet.

therapy de-escalation in stage iia/b seminoma represents an unmet need in clinical practice; efficacy of modern standard of care therapies for these patients is high and only a few patients show disease recurrence but short- and long-term toxicities are a major concern. the magnitude of long-term toxicities is often associated with the intensity of the prescribed treatment modality. a higher cumulative dose of chemotherapy agents and radiation dose has been linked to a sharp increase in long-term sequelae. combining treatment modalities and diversifying toxicity may thus provide an opportunity to limit long-term treatment sequelae. in this trial carboplatin, cisplatin and etoposide are the investigational medicine products (imps). they are all medications with a marketing authorization for several solid tumor types and are standard practice in the treatment of testicular cancer in switzerland and in the european union (eu). radiotherapy is also a standard therapy in this indication. however, the trial investigates a stage-adapted (stage iia or iib) de-escalation of these standard treatments in the context of a multimodality treatment with chemo- and radiotherapy. the goal is to safely de-escalate treatment while maintaining/enhancing efficacy, which is not a standard practice yet. the sakk 01/18 trial is designed with the aim to answer these three questions: * can the dose of involved-node radiotherapy be safely reduced in the context of multimodality treatment with chemo- and radiotherapy? * can a more potent chemotherapy in the form of cisplatin/etoposide reduce the rate of distant failure in comparison to carboplatin? * can a combination of cisplatin/etoposide and involved-node radiotherapy pose a potent treatment regime for patients with recurrence after adjuvant carboplatin or radiotherapy for stage i seminoma? furthermore, as active surveillance is becoming standard of care in stage i seminoma, it is projected that the amount of patients in need of treatment with stage iia/b disease will rise, due to more patients developing disease progression during active surveillance. the trial design, trial treatment and trial specifics are a consensus among the swiss urogenital tumors project group and the swiss radio-oncology section from the swiss group for clinical cancer research (sakk) and the german testicular cancer study group (gtcsg).

Eligibility criteria:
inclusion criteria: * written informed consent according to ich/gcp (international council on harmonization/good clinical practice) regulations before registration and prior to any trial specific procedures * histologically confirmed classical seminoma treated with primary inguinal orchidectomy or partial orchidectomy * patients with a seminoma stage iia or iib, either newly diagnosed or recurrent after primary active surveillance, adjuvant carboplatin or radiotherapy for stage i disease. the tumor stage is pt1-4 cn1-2 cm0 according to uicc tnm 8th edition 2016. patients with a recurrent seminoma stage iia or iib are only eligible in case of progression under active surveillance or recurrence after adjuvant carboplatin or radiotherapy for stage i disease * stage iia, in patients with equivocal lymph node enlargement, needs to be confirmed with a repeated ct/mri scan of the abdomen (suggested timeframe: 4 weeks after the previous scan) in order to rule out false positive lymph node enlargement. patients with a prior malignancy treated with curative intention are eligible if all treatment of that malignancy was completed at least 5 years before registration and the patient has no evidence of disease at registration. less than 5 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence. patients with a germ cell neoplasia in situ (gcnis) or contralateral localized treated seminoma are eligible * diagnostic ct or mri or fdg-pet-ct of the chest, abdomen and pelvis within 28 days prior to registration, showing stage iia/b disease. i.v. contrast medium has to be administered * age ≥ 18 years * who performance status 0-2 * baseline pro questionnaires have been completed * adequate bone marrow function: neutrophil count ≥ 1.0 x 109/l, platelet count ≥ 100x 109/l * adequate renal function: creatinine clearance ≥ 60 ml/min calculated according to the ckd-epi (chronic kidney disease epidemiology collaboration) formula * patient agrees to use highly effective contraception and not to donate sperm or to father a child during trial treatment and during 12 months thereafter. patient has been proposed sperm conservation. exclusion criteria * any other histological component than seminoma * elevated levels of alpha-1-fetoprotein afp (≥ 2x uln) * involved nodes (metastatic) in previously irradiated localizations in the abdomen or pelvis * any anti-cancer therapy after primary tumor resection in patients presenting with primary stage iia/b seminoma * any serious underlying medical condition (i.e. current renal insufficiency, severe hepatic insufficiency, severe bone marrow dysfunction, tumor bleeding, major hearing defects) or serious co-morbidity which could impair the ability of the patient to participate in the trial (according to investigator's judgment) * any treatment in a clinical trial within 28 days prior to registration * any concomitant drugs contraindicated for use with the trial drugs according to the approved product information or contraindicated for use with radiotherapy * known hypersensitivity to trial drugs or to any component of the trial drugs * any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications. additional german specific exclusion criteria - not to be considered for swiss patients * patient who is dependent on the sponsor or the investigators according to ich/gcp e6(r2), guideline * patient who has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities according to § 40a (2) amg.

Keywords: seminoma stage iia/b seminoma radio-chemotherapy phase ii trial testicular cancer