Clinical trial NCT03489616: Chemotherapy Combination With Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients
Official title: Chemotherapy Combination With Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients Without Progression After First-line Chemotherapy: a Prospective Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2018-04-05
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether chemotherapy combination with local radiotherapy and rhGM-CSF is safe, effective in the treatment of oligometastatic stage IV NSCLC patients.

Detailed description: The purpose of this study is to determine whether chemotherapy combination with local radiotherapy and recombined human granulocyte-macrophage colony stimulating factor(rhGM-CSF) is safe, effective in the treatment of oligometastatic stage IV NSCLC patients who were PR or SD after first-line chemotherapy，and to observe the abscopal effect, whether the scheme can improve PFS and OS.

Eligibility criteria: Inclusion Criteria:

1. Stage IV NSCLC patients without clear driving genes who were PR or SD after standard first-line chemotherapy;
2. Patients who were oligometastasis evaluated by PET-CT or other examinations after first-line chemotherapy. Eligible patients should have 2 to 5 distant metastases (at least 2 metastases were suitable for low fractionated radiotherapy). At least one distant measurable lesion outside the radiation sites.
3. Age varied from 18 to 75 years old.
4. ECOG performance status 0-2.
5. Expected lifespan ≥3 months.
6. Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥90 g/L.
7. Able to understand and give written informed consent and comply with study procedures.

Exclusion criteria

1. Allergy of rhGM-CSF and its accessories.
2. Disease of systemic immune or immune disorders.
3. Histology confirmed small cell carcinoma or other malignant compositions in the cancer tissue.
4. Patients with thrombotic disease or platelets ≥600×109/L
5. Cancer history within 5 years apart from NSCLC before enrollment.
6. Tumor related immunotherapy within 4 weeks, including but not limited to immune cell therapy, tumor vaccine therapy, Immune checkpoint therapy, and other immunomodulators (such as thymosin, lentinan) except for rhGM-CSF.
7. The abnormality of kidney , heart or lung functions（serum creatinine, Cr\>177mol/L; serum AST or ALT more than 2 times above normal limits; total bilirubin, TBIL\>34mol/L）.
8. HIV virus, hepatitis C virus or T lymphocyte virus (type1 or type 2) infection and active hepatitis or other uncontrolled infections.
9. Women in pregnancy or lactation.
10. Others who do not meet the inclusion criteria.

Primary outcomes:
measure: PFS
timeFrame: 2 years
Secondary outcomes:
measure: Abscopal effect rate
timeFrame: At the time point of 4 weeks after completion of rhGM-CSF
measure: OS
timeFrame: 2 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
city: Jinan
country: China
facility: SHANDONG Cancer Hospital
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: JINMING YU, doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, Friedman K, Ponzo F, Babb JS, Goldberg J, Demaria S, Formenti SC. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol. 2015 Jul;16(7):795-803. doi: 10.1016/S1470-2045(15)00054-6. Epub 2015 Jun 18.
citation: Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.