Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma. A Multicenter, Open Label Phase II Trial With Two Cohorts
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 135
- 试验地点
- 19
- 主要终点
- Progression free survival (PFS) at 3 years
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Arm with 2 cohorts
Cohort 1: Primary stage IIA and recurrent stage IIA seminoma after active surveillance for stage I:
- Within 7 days after registration, the patients will receive one infusion of carboplatin AUC (Area under the curve) 7 at day 1 of trial treatment, followed 3 weeks later by 12 x 2 Gy involved-node radiation therapy (RT). RT should ideally start on day 22 (range: day 19-25) from the date of carboplatin administration, preferably on a Monday.
Cohort 2: Primary stage IIB and recurrent stage IIB seminoma after active surveillance for stage I OR stage IIA/B seminoma after adjuvant carboplatin or radiotherapy for stage I:
- Within 7 days after registration, the patients will receive one cycle of etoposide 100 mg/m2/d + cisplatin 20 mg/m2/d at days 1 to 5 of trial treatment, followed 3 weeks later by 15 x 2 Gy involved-node radiation therapy. RT should ideally start on day 22 (range: day 19-25) from the date of chemotherapy start, preferably on a Monday.
干预措施: Carboplatin (Drug)
Arm with 2 cohorts
Cohort 1: Primary stage IIA and recurrent stage IIA seminoma after active surveillance for stage I:
- Within 7 days after registration, the patients will receive one infusion of carboplatin AUC (Area under the curve) 7 at day 1 of trial treatment, followed 3 weeks later by 12 x 2 Gy involved-node radiation therapy (RT). RT should ideally start on day 22 (range: day 19-25) from the date of carboplatin administration, preferably on a Monday.
Cohort 2: Primary stage IIB and recurrent stage IIB seminoma after active surveillance for stage I OR stage IIA/B seminoma after adjuvant carboplatin or radiotherapy for stage I:
- Within 7 days after registration, the patients will receive one cycle of etoposide 100 mg/m2/d + cisplatin 20 mg/m2/d at days 1 to 5 of trial treatment, followed 3 weeks later by 15 x 2 Gy involved-node radiation therapy. RT should ideally start on day 22 (range: day 19-25) from the date of chemotherapy start, preferably on a Monday.
干预措施: Cisplatin (Drug)
Arm with 2 cohorts
Cohort 1: Primary stage IIA and recurrent stage IIA seminoma after active surveillance for stage I:
- Within 7 days after registration, the patients will receive one infusion of carboplatin AUC (Area under the curve) 7 at day 1 of trial treatment, followed 3 weeks later by 12 x 2 Gy involved-node radiation therapy (RT). RT should ideally start on day 22 (range: day 19-25) from the date of carboplatin administration, preferably on a Monday.
Cohort 2: Primary stage IIB and recurrent stage IIB seminoma after active surveillance for stage I OR stage IIA/B seminoma after adjuvant carboplatin or radiotherapy for stage I:
- Within 7 days after registration, the patients will receive one cycle of etoposide 100 mg/m2/d + cisplatin 20 mg/m2/d at days 1 to 5 of trial treatment, followed 3 weeks later by 15 x 2 Gy involved-node radiation therapy. RT should ideally start on day 22 (range: day 19-25) from the date of chemotherapy start, preferably on a Monday.
干预措施: Etoposide (Drug)
结局指标
主要结局
Progression free survival (PFS) at 3 years
时间窗: From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 3 years after registration
PFS is defined as the time from registration until one of the following events occurs: * Progressive disease or relapse, defined as progression according to the modified trial-specific version of RECIST 1.1 or a rising level of the tumor marker beta-hCG (beta human chorionic gonadotropin) over the ULN (Upper limit of normal), confirmed by a second measurement. Presence of non-seminoma germ cell tumor has to be excluded in the latter case * Death from any cause.
次要结局
- Seminoma-specific survival(From the date of registration until the date of death due to seminoma, assessed up to 20 years after registration)
- Method of detection of progression(at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration)
- Progression free survival (PFS)(From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 20 years after registration)
- Time to progression (TTP)(From the date of registration until the date of progressive disease, relapse or death due to progression, whichever occurs first, assessed up to 20 years after registration)
- Response rate (RR)(at 3 months and 3 years after registration)
- Overall Survival (OS)(From the date of registration until the date of death from any cause, assessed up to 20 years after registration)
- Time to distant metastasis(From the date of registration until the date of first occurrence of distant metastasis, assessed up to 20 years after registration)
- Localization of progression(at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration)
- Time to next treatment(From the date of registration until the date of start of any new anticancer therapy for progressive seminoma, assessed up to 20 years after registration)