RTOG 937: Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extra-Cranial Irradiation for Extensive Disease Small Cell Lung Cancer (ED-SCLC)

Summary

PCi will be delivered at 2.5 Gy per fraction to 25 Gy to all patients. Patients on arm 2 will be
treated with radiation to the mediastinum and residual metastatic lesions with 3D-CRT at 3 Gy per
fraction to 45 Gy. This dose is biologically similar to 60 Gy delivered in 30 fractions. an
alternative biologically similar regimen of 40 Gy in 10 fractions is acceptable.

Schema

S Response to Treatment R arm 1: Prophylactic Cranial irradiation
T 1. Complete Response (CR) a 2.5 Gy per fraction for a total of 25 Gy
R 2. Partial Response (PR) n
a D arm 2: Prophylactic Cranial irradiation
T o 2.5 Gy per fraction for a total of 25 Gy
i number of Metastatic Lesions M and
F 1. 1 i Consolidative Radiation to
Y 2. 2-4 Z Locoregional and Residual Metastatic Disease
e 45 Gy at 3 Gy per fraction*
*acceptable alternative regimens: 30-40 Gy in 10 fractions

Patient Population:
Patients with extensive disease small cell lung cancer, excluding CnS metastases; patients must have had radiographic evidence of 1-3 extra-cranial metastatic lesions prior to platinum-based chemotherapy anD have had radiographic partial or complete response to chemotherapy in a minimum of one site of disease and no progression in any site.

Required Sample Size: 154 for the study. uTSW and affiliates will enroll 10 patients to this study.

Participant Eligibility

3.1 Conditions for Patient Eligibility
3.1.1 Pathologically (histologically or cytologically) proven diagnosis of extensive disease small cell
lung cancer without brain metastases and with 1-4 metastatic lesions; Note: This does NOT
include patients initially diagnosed with LD-SCLC who have progressed.
3.1.2 Patients must have completed 4-6 cycles of platinum-based chemotherapy.
3.1.3 Patients must be registered on study within 8 weeks of completing chemotherapy.
3.1.4 Prior to chemotherapy (at diagnosis), patients must have extensive stage disease with 1-4
extracranial metastatic lesions (no brain metastases). For example, the patient could have 2
lesions in the liver and 2 in the contralateral lung; or 1 in the bone, 1 in the contralateral lung,
and 2 in the liver; or 3 liver lesions and 1 in the bone, etc. Lesion is not defined as
* organ
* .
The patient should have no clinical signs or symptoms of CNS metastases. Brain imaging is not
required prior to chemotherapy if the patient is asymptomatic; however, brain imaging is
required and must be negative for metastases prior to study entry. Extent of disease will be
based on the following minimum diagnostic workup:
3.1.4.1 History/physical examination;
3.1.4.2 CT of the chest and abdomen with contrast or PET/CT. ;
3.1.5 After chemotherapy, patients will be restaged using the following diagnostic work up :

* History/physical examination;

* CT of the chest and abdomen with contrast (does not have to be done if the patient has
had a PET/CT scan within 8 weeks prior to registration);

* Bone scan (does not have to be done if the patient has had a PET scan within 8 weeks
prior to registration);

* MRI of the brain or CT with contrast of the brain, if MRI is contraindicated.
Patients must have:

* no CNS metastases;

* radiographic partial or complete response to chemotherapy in a minimum of 1 site of
disease using RECIST criteria (see Section 11.3.2); Note: if radiation has been delivered
to primary disease with chemotherapy, there must be complete or partial response in at
least 1 of the sites that has not been treated with radiation.

* no progression in any site;

* for the purposes of stratification, a response to treatment is only considered a
* CR
* if the
patient has had a complete response in all sites of measurable disease.
3.1.6 Patients who have had thoracic radiation concurrently or prior to chemotherapy for the current
diagnosis and meet all other eligibility criteria are eligible for the study but will not receive
mediastinal radiation per protocol.
3.1.6.1 Measurements for all pre- and post-chemotherapy measurable disease must be submitted.
3.1.7 Zubrod Performance Status 0-2;
3.1.8 Age >= 18;
3.1.9 For patients who will be treated with radiation to the liver, adequate hepatic function, defined as
follows:
3.1.9.1 Serum ALT and AST within 2.5 X ULN within 1 week prior to registration;
3.1.9.2 Serum bilirubin < 1.5 X ULN within 1 week prior to registration.
3.1.10 For patients who will be treated with radiation to the kidneys, adequate renal function defined
as a serum creatinine < 1.5 X ULN within 1 week of registration;
3.1.11 CBC/differential obtained within 1 week prior to registration, with adequate bone marrow
function defined as follows:
3.1.11.1 Absolute neutrophil count (ANC) >= 1,000 cells/mm3;
3.1.11.2 Platelets >= 75,000 cells/mm3;
3.1.11.3 Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
8.0 g/dl is acceptable.).
3.1.12 For women of childbearing potential, a negative serum pregnancy test within 1 week of
registration;
3.1.13 All toxicities related to chemotherapy must be resolved to < grade 1 prior to initiation of study
therapy (with the exception of neuropathy and alopecia, which may take a longer period to
recover). Laboratory abnormalities, with the exception of those specified in Sections 3.1.9,
3.1.10, and 3.1.11, are allowed if they are not deemed clinically significant.
3.1.14 Patients must provide study-specific informed consent prior to study entry.