Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    SAKK 01/18
Previous Study | Return to List | Next Study

Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03937843
Recruitment Status : Recruiting
First Posted : May 6, 2019
Last Update Posted : December 3, 2019
Sponsor:
Collaborator:
German Testicular Cancer Study Group
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.

Condition or disease Intervention/treatment Phase
Seminoma Testicular Cancer Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Phase 2

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: A multicenter, open label phase II trial with two cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma. A Multicenter, Open Label Phase II Trial With Two Cohorts
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2046

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Carboplatin
Patients in cohort 1 will receive a 60-minute i.v. infusion of carboplatin AUC 7 at day 1 of treatment.

Drug: Cisplatin

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.

Drug: Etoposide

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 Measures :
  1. Progression free survival (PFS) at 3 years [ 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 ]

    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 :
  1. Response rate (RR) [ Time Frame: at 3 months and 3 years after registration ]

    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.


  2. 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 ]
  3. Time to progression (TTP) [ 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 ]

    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.


  4. Overall Survival (OS) [ Time Frame: From the date of registration until the date of death from any cause, assessed up to 20 years after registration ]
    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.

  5. Seminoma-specific survival [ Time Frame: From the date of registration until the date of death due to seminoma, assessed up to 20 years after registration ]
    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.

  6. Time to distant metastasis [ Time Frame: From the date of registration until the date of first occurrence of distant metastasis, assessed up to 20 years after registration ]
    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.

  7. Time to next treatment [ 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 ]
    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.

  8. Localization of progression [ Time Frame: at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration ]

    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

  9. Method of detection of progression [ Time Frame: at the date of the first occurrence of progressive disease, assessed from registration up to 20 years after registration ]

    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03937843


Contacts
Layout table for location contacts
Contact: Corinne Schär, PhD +41 31 389 91 91 trials@sakk.ch

Locations
Layout table for location information
Switzerland
Universitaetsspital-Basel Recruiting
Basel, Switzerland, CH-4031
Contact: Alexandros Papachristofilou, MD    41-61-265-4946    alexandros.papachristofilou@usb.ch   
Principal Investigator: Alexandros Papachristofilou, MD         
Istituto Oncologico della Svizzera Italiana (IOSI) Recruiting
Bellinzona, Switzerland, CH-6500
Contact: Ngwa Che Azinwi, MD    +41 91 811 89 32    ngwache.azinwi@eoc.ch   
Principal Investigator: Ngwa Che Azinwi, MD         
Inselspital Bern Recruiting
Bern, Switzerland, 3010
Contact: Mohamed Shelan, MD    +41 31 632 29 70    mohamed.shelan@insel.ch   
Principal Investigator: Mohamed Shelan, MD         
Kantonsspital Graubuenden Recruiting
Chur, Switzerland, 7000
Contact: Richard Cathomas, MD    +41 81 256 66 95    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Contact: Richard Cathomas, MD    +41 81 256 66 95    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Centre Hospitalier Universitaire Vaudois CHUV Recruiting
Lausanne, Switzerland, CH-1011
Contact: Dominik Berthold, MD    +41 21 314 80 83    Dominik.Berthold@chuv.ch   
Principal Investigator: Dominik Berthold, MD         
Hopital de Sion Recruiting
Sion, Switzerland, 1951
Contact: Kaouthar Khanfir, MD    +41 27 603 87 72    kaouthar.khanfir@hopitalvs.ch   
Principal Investigator: Kaouthar Khanfir, MD         
Kantonsspital - St. Gallen Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Paul Martin Putora, MD    +41 71 494 22 68    paulmartin.putora@kssg.ch   
Principal Investigator: Paul Martin Putora, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, 8401
Contact: Miklos Pless, Prof    +41 52 266 36 40    miklos.pless@ksw.ch   
Principal Investigator: Miklos Pless, Prof         
UniversitätsSpital Zürich Recruiting
Zürich, Switzerland, 8091
Contact: Anja Lorch, Prof    +41 43 253 02 50    anja.lorch@usz.ch   
Principal Investigator: Anja Lorch, Prof         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
German Testicular Cancer Study Group
Investigators
Layout table for investigator information
Study Chair: Alexandros Papachristofilou, MD Universitätsspital Basel
Layout table for additonal information
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT03937843    
Other Study ID Numbers: SAKK 01/18
2019‐000514‐11 ( EudraCT Number )
First Posted: May 6, 2019    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: December 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Swiss Group for Clinical Cancer Research:
Seminoma
Stage IIA/B seminoma
Radio-chemotherapy
Phase II trial
Testicular Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Seminoma
Testicular Neoplasms
Germinoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action