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Carboplatin Chemotherapy and Involved Node Radiotherapy in Stage IIA/B Seminoma

18 Years
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Trial Information

Carboplatin Chemotherapy and Involved Node Radiotherapy in Stage IIA/B Seminoma


1. Disease background

Testicular cancers are the most common malignancies in men aged between 18-35 years. Of
those, seminoma is the most frequent as it accounts for about half of all testicular
cancers. Seminoma is classified according to the involvement of and degree of spreading
to lymph nodes and to the lung or other organs. Around 10% of all seminoma patients are
diagnosed with stage IIA/B disease. Stage IIA patients have one or more enlarged
regional lymph nodes, 2 cm or less in greatest dimension, without evidence of distant
disease (cN1 cM0). Stage IIB patients have one or more enlarged regional lymph nodes
more than 2 cm but not more than 5 cm in greatest dimension, without evidence of
distant disease (cN2 cM0). Paraaortic, interaortocaval, para-/pre-/retrocaval and
pre-/retroaortic lymph nodes are considered regional. Intrapelvic, external iliac and
inguinal lymph nodes are considered regional only after scrotal or inguinal surgery.

Seminoma stage IIA/B is highly responsive to chemotherapy or radiation therapy and the
progression free survival at 5 or 6 years with such treatments is between 87-95%.
Supra-diaphragmatic lymph nodes are the usual site of tumor recurrence after radiation
therapy, while local failure or tumor persistence in paraaortic lymph nodes is
predominant after chemotherapy.

2. Therapy background

Current standard of therapy in patients with stage IIA/B seminoma involves either large
volume paraaortic and ipsilateral pelvic radiation therapy ("dogleg field") or three
cycles of chemotherapy with BEP (Bleomycin, Etoposide, Cisplatin). While both treatment
modalities offer high rates of progression free survival and overall survival, they
also potentially bear the risk of unwanted events during and following the treatment.
Large volume radiation therapy is associated with fatigue, nausea and vomiting during
treatment. BEP chemotherapy causes transient fatigue, cytopenia and hair loss. In terms
of late adverse events, radiotherapy increases the risk for permanent kidney and bowel
damage, while BEP chemotherapy may harm kidneys, lungs, heart and the inner ear. Both
therapy modalities may also lead to secondary tumors. Data on late undesirable effects
of large field radiation therapy or intensive chemotherapy will become available in the
future at the conclusion of long term follow-up analyses of the recent trials. Thus,
the current research on seminoma focuses on minimizing short and long term
treatment-related morbidity.

3. Previous trials

Therapy de-escalation has been tested and been proven effective in stage I testicular
seminoma patients. For many years, the standard of care for these patients was
paraaortic radiation therapy. The trial by Oliver et al. demonstrated the
non-inferiority of single dose carboplatin chemotherapy in comparison to paraaortic
irradiation in terms of tumor control in patients with stage I seminoma. Although the
trial did not present long term data and the demonstration of a lower toxicity profile
with carboplatin compared to paraaortic irradiation is still lacking, many clinicians
have already switched their treatment strategy to carboplatin chemotherapy in seminoma
stage I patients, in hope that this treatment will produce less negative late effects
than radiation therapy. Based on these results, we think that a similar therapy
de-escalation approach could be attractive in patients with stage II disease.

4. Rationale for performing the trial

Therapy de-escalation for stage IIA/B seminoma has been recently tested in a prospective
phase II trial with the use of 3 cycles (for stage IIA) or 4 cycles (for stage IIB) of
carboplatin chemotherapy. However, this regime is actually not considered an acceptable
treatment because of a relapse rate of 18% at three years. In this trial, all relapsed
patients experienced tumor recurrence in the lymph nodes that were initially involved within
3 years following treatment. Thus, while chemotherapy de-escalation with carboplatin leads
to a good systemic disease's control, the local control in the involved nodes remains a

On the other hand, no relapse occurs in the initially involved lymph nodes in seminoma IIA/B
patients which were treated with large volume irradiation, although 5% of the patients
developed distant relapses.

Therefore, one possible way to raise progression free survival in the involved lymph nodes
areas to an acceptable level in a therapy de-escalation protocol would be to combine
suboptimal carboplatin chemotherapy (1 cycle) with a limited volume of radiation therapy
targeting the involved nodes (30 or 36 Gy for stage IIA or IIB, respectively).

It is expected that this combination will trigger less side effects than any of the standard
therapies. Previous trials demonstrated that single agent carboplatin is not associated with
an increase in the number of adverse events for up to 9 years post chemotherapy. The
application of small volume, involved node radiation therapy should avoid damage to viscera
and kidneys. Furthermore, the risk for secondary malignancies will likely be reduced because
of the low-intensity chemotherapy and dramatically shrunk irradiation field.

This is a single arm trial, in which both stage IIA and IIB patients are included, since all
current international treatment recommendations are valid for both disease stages. Selecting
exclusively one disease stage for trial inclusion would greatly hamper the feasibility of
such a trial.

The trial design, trial treatment and trial specifics are a consensus among the Swiss
Urogenital Tumors Project Group, the Swiss Radio-oncology Section and the German Testicular
Cancer Study Group.

If the proposed therapy scheme proves to be effective and safe, it will provide a
significantly relevant treatment alternative to large volume radiotherapy and intense
chemotherapy, and may become the new standard of care for patients with seminoma stage

Inclusion Criteria:

- Patient has given written informed consent before registration.

- Histologically confirmed classical seminoma treated with primary inguinal
orchidectomy 12 weeks or less before registration.

- Tumor stage is pT1-4 cN1-2 cM0 according to UICC TNM 2009.

- Multi-slice CT of the chest, abdomen and pelvis or a FDG-PET-CT within 4 weeks prior
to patient registration, showing stage IIA/B disease. Oral and i.v. contrast have to
be administered.

- Age ≥ 18 years.

- WHO performance status 0-2.

- Adequate hematological values: neutrophils ≥ 1.0 x 109/L, platelets ≥ 100x 109/L.

- Adequate renal function (calculated creatinine clearance ≥ 50 ml/min, according to
the formula of Cockcroft-Gault).

- Patient agrees not to father a child during trial treatment and during 12 months

- Patient has been proposed sperm conservation.

- Patient compliance and geographic proximity allow proper staging and follow-up for at
least 3 years.

Exclusion Criteria:

- Previous or concurrent malignancy within 5 years with the exception of localized
non-melanoma skin cancer.

- Psychiatric disorder precluding understanding of information on trial-related topics
or giving informed consent or interfering with compliance for treatment schedule.

- Mixed histology seminoma.

- Elevated levels of AFP (≥ULN).

- Any prior abdominal/pelvic radiotherapy (RT).

- Any anti-cancer therapy after primary tumor resection.

- Any treatment in a clinical trial within 30 days of trial entry.

- Any serious underlying medical condition or serious co-morbidity (at the judgment of
the investigator) which could impair the ability of the patient to participate in the

- Any contraindication for the trial drug (for example, known hypersensitivity to trial
drug or to any other co-component of the trial drug, past or current renal
insufficiency, severe hepatic insufficiency, severe bone marrow dysfunction, tumor
bleeding, major hearing defects).

- Any concomitant drugs contraindicated for use with the trial drug according to the
approved product information (for example, nephrotoxic or ototoxic medicines).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival (PFS)

Outcome Description:

success/failure of PFS

Outcome Time Frame:

at 3 years (± 1 month)

Safety Issue:


Principal Investigator

Alexandros Papachristofilou, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospital, Basel, Switzerland


Switzerland: Swissmedic

Study ID:

SAKK 01/10



Start Date:

May 2012

Completion Date:

June 2035

Related Keywords:

  • Seminoma
  • Seminoma IIA/B
  • Carboplatin
  • RT
  • Seminoma