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Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma

Primary Purpose

Seminoma, Testicular Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Carboplatin
Cisplatin
Etoposide
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Seminoma focused on measuring Seminoma, Stage IIA/B seminoma, Radio-chemotherapy, Phase II trial, Testicular Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Vivantes Klinikum Am Urban
  • Helios Klinikum Berlin-Buch
  • Evang. Kliniken Essen-Mitte
  • Universitätsklinikum Hamburg-Eppendorf
  • ASKLEPIOS Kliniken
  • RKH Klinikum Ludwigsburg
  • Rotkreuzklinikum München
  • Universitätsklinikum Tübingen
  • Universitätsklinikum Ulm
  • Universitaetsspital-Basel
  • Istituto Oncologico della Svizzera Italiana (IOSI)
  • Inselspital Bern
  • Kantonsspital Graubuenden
  • Kantonsspital Graubünden
  • Centre Hospitalier Universitaire Vaudois CHUV
  • Hopital de Sion
  • Kantonsspital - St. Gallen
  • Kantonsspital Winterthur
  • UniversitätsSpital Zürich

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm with 2 cohorts

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression free survival (PFS) at 3 years
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.

Secondary Outcome Measures

Response rate (RR)
The response is categorized according to the modified trial-specific version of RECIST 1.1 measurability criteria as: complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD). The response rate is defined as proportion of patients with CR or PR on imaging assessment and without rising beta-hCG. Patients with CR, PR and SD on imaging assessment, but with confirmed rising beta-hCG will not be counted as responders, if the presence on non-seminoma germ cell tumor was excluded. Response rate will be evaluated at 3 months and 3 years after registration.
Progression free survival (PFS)
Time to progression (TTP)
TTP is defined as the time from registration until documented PD or relapse according to the modified trial-specific version of RECIST 1.1 or death due to progression, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment showing non-progression before the start of a new therapy, if any.
Overall Survival (OS)
OS is defined as the time from registration to the date of death from any cause. Patients who did not experience an event will be censored at the last known time they were known to be alive.
Seminoma-specific survival
Seminoma-specific survival is defined as the time from registration to the date of death due to seminoma. Patients who did not experience an event will be censored at the last known time they were known to be alive.
Time to distant metastasis
Time to distant metastasis is defined as the time from registration until first occurrence of distant metastasis. Patients not experiencing an event will be censored at the date of the last available assessment.
Time to next treatment
Time to next treatment is defined as the time from registration to the start of any new anticancer therapy for progressive seminoma. Patients not receiving any new treatment are censored at the last date they were known to be alive.
Localization of progression
The localization of progression is defined as the first localization where progressive disease is detected. It is divided into the following sites: Initially involved lymph node area Non-initially involved paraaortic & pelvic lymph node area Supradiaphragmatic lymph node area Organ involvement (lung, liver, bones, etc.) Multiple sites simultaneously
Method of detection of progression
The method of detection of progression is defined as the first method used to detect the first progression event and comprises the following categories: Physical examination (inspection, palpation, etc.) Rising beta-hCG tumor marker CT imaging Ultrasound imaging X-ray imaging Other imaging (e. g. MRI, PET-CT)

Full Information

First Posted
April 29, 2019
Last Updated
June 23, 2023
Sponsor
Swiss Group for Clinical Cancer Research
Collaborators
German Testicular Cancer Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT03937843
Brief Title
Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma
Official Title
Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma. A Multicenter, Open Label Phase II Trial With Two Cohorts
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 29, 2019 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2046 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research
Collaborators
German Testicular Cancer Study Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Seminoma, Testicular Cancer
Keywords
Seminoma, Stage IIA/B seminoma, Radio-chemotherapy, Phase II trial, Testicular Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
A multicenter, open label phase II trial with two cohorts
Masking
None (Open Label)
Allocation
N/A
Enrollment
135 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm with 2 cohorts
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Patients in cohort 1 will receive a 60-minute i.v. infusion of carboplatin AUC 7 at day 1 of treatment.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Patients in cohort 2 will receive on day 1 to day 5: a 60-minutes i.v. infusion of etoposide 100mg/m2 per day followed by a 60-120 minutes i.v. infusion of cisplatin 20mg/m2 per day.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Patients in cohort 2 will receive on day 1 to day 5: a 60-minutes i.v. infusion of etoposide 100mg/m2 per day followed by a 60-120 minutes i.v. infusion of cisplatin 20mg/m2 per day.
Primary Outcome Measure Information:
Title
Progression free survival (PFS) at 3 years
Description
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.
Time Frame
From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 3 years after registration
Secondary Outcome Measure Information:
Title
Response rate (RR)
Description
The response is categorized according to the modified trial-specific version of RECIST 1.1 measurability criteria as: complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD). The response rate is defined as proportion of patients with CR or PR on imaging assessment and without rising beta-hCG. Patients with CR, PR and SD on imaging assessment, but with confirmed rising beta-hCG will not be counted as responders, if the presence on non-seminoma germ cell tumor was excluded. Response rate will be evaluated at 3 months and 3 years after registration.
Time Frame
at 3 months and 3 years after registration
Title
Progression free survival (PFS)
Time Frame
From the date of registration until the date of progressive disease, relapse or death, whichever occurs first, assessed up to 20 years after registration
Title
Time to progression (TTP)
Description
TTP is defined as the time from registration until documented PD or relapse according to the modified trial-specific version of RECIST 1.1 or death due to progression, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment showing non-progression before the start of a new therapy, if any.
Time Frame
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
Title
Overall Survival (OS)
Description
OS is defined as the time from registration to the date of death from any cause. Patients who did not experience an event will be censored at the last known time they were known to be alive.
Time Frame
From the date of registration until the date of death from any cause, assessed up to 20 years after registration
Title
Seminoma-specific survival
Description
Seminoma-specific survival is defined as the time from registration to the date of death due to seminoma. Patients who did not experience an event will be censored at the last known time they were known to be alive.
Time Frame
From the date of registration until the date of death due to seminoma, assessed up to 20 years after registration
Title
Time to distant metastasis
Description
Time to distant metastasis is defined as the time from registration until first occurrence of distant metastasis. Patients not experiencing an event will be censored at the date of the last available assessment.
Time Frame
From the date of registration until the date of first occurrence of distant metastasis, assessed up to 20 years after registration
Title
Time to next treatment
Description
Time to next treatment is defined as the time from registration to the start of any new anticancer therapy for progressive seminoma. Patients not receiving any new treatment are censored at the last date they were known to be alive.
Time Frame
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
Title
Localization of progression
Description
The localization of progression is defined as the first localization where progressive disease is detected. It is divided into the following sites: Initially involved lymph node area Non-initially involved paraaortic & pelvic lymph node area Supradiaphragmatic lymph node area Organ involvement (lung, liver, bones, etc.) Multiple sites simultaneously
Time Frame
at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration
Title
Method of detection of progression
Description
The method of detection of progression is defined as the first method used to detect the first progression event and comprises the following categories: Physical examination (inspection, palpation, etc.) Rising beta-hCG tumor marker CT imaging Ultrasound imaging X-ray imaging Other imaging (e. g. MRI, PET-CT)
Time Frame
at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandros Papachristofilou, MD
Organizational Affiliation
Universitätsspital Basel
Official's Role
Study Chair
Facility Information:
Facility Name
Vivantes Klinikum Am Urban
City
Berlin
ZIP/Postal Code
10967
Country
Germany
Facility Name
Helios Klinikum Berlin-Buch
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Evang. Kliniken Essen-Mitte
City
Essen
ZIP/Postal Code
45136
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
ASKLEPIOS Kliniken
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
RKH Klinikum Ludwigsburg
City
Ludwigsburg
ZIP/Postal Code
71640
Country
Germany
Facility Name
Rotkreuzklinikum München
City
München
ZIP/Postal Code
80364
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana (IOSI)
City
Bellinzona
ZIP/Postal Code
CH-6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Kantonsspital Graubuenden
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
Kantonsspital Graubünden
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois CHUV
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Hopital de Sion
City
Sion
ZIP/Postal Code
1951
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
CH-9007
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
8401
Country
Switzerland
Facility Name
UniversitätsSpital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma

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