Chemotherapy Combination With Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients

Not Applicable

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Biological: rhGM-CSF; Drug: Pemetrexed; Radiation: Local Radiotherapy; Drug: Single agent

• Registration Number: NCT03489616
• Lead Sponsor: Shandong Cancer Hospital and Institute

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.

Study Timeline

• Study Start: 2018-01-15
• Status Verified: 2018-03
• Study First Submitted: 2018-03-29
• Study First Submitted QC: 2018-04-04
• Last Update Submitted: 2018-04-04
• Study First Posted: 2018-04-05
• Last Update Posted: 2018-04-05
• Primary Completion: 2019-07-01
• Study Completion: 2019-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Radiotherapy+chemotherapy+ rhGM-CSF	Pemetrexed	Patients with PR or SD after first-line chemotherapy will be treated with pemetrexed on d1 (500mg/m2) or other single agent on d1, d8. Local radiotherapy dose will be\> 4Gy per time（or BED \>45Gy） from day 2 to day 15 in a cycle of 21 days. Subcutaneous injection of rhGM-CSF (200ug/m² per day) will be executed 24 hours after chemotherapy. Repeat in the second metastatic lesions.
Radiotherapy+chemotherapy+ rhGM-CSF	Single agent	Patients with PR or SD after first-line chemotherapy will be treated with pemetrexed on d1 (500mg/m2) or other single agent on d1, d8. Local radiotherapy dose will be\> 4Gy per time（or BED \>45Gy） from day 2 to day 15 in a cycle of 21 days. Subcutaneous injection of rhGM-CSF (200ug/m² per day) will be executed 24 hours after chemotherapy. Repeat in the second metastatic lesions.
Radiotherapy+chemotherapy+ rhGM-CSF	rhGM-CSF	Patients with PR or SD after first-line chemotherapy will be treated with pemetrexed on d1 (500mg/m2) or other single agent on d1, d8. Local radiotherapy dose will be\> 4Gy per time（or BED \>45Gy） from day 2 to day 15 in a cycle of 21 days. Subcutaneous injection of rhGM-CSF (200ug/m² per day) will be executed 24 hours after chemotherapy. Repeat in the second metastatic lesions.
Radiotherapy+chemotherapy+ rhGM-CSF	Local Radiotherapy	Patients with PR or SD after first-line chemotherapy will be treated with pemetrexed on d1 (500mg/m2) or other single agent on d1, d8. Local radiotherapy dose will be\> 4Gy per time（or BED \>45Gy） from day 2 to day 15 in a cycle of 21 days. Subcutaneous injection of rhGM-CSF (200ug/m² per day) will be executed 24 hours after chemotherapy. Repeat in the second metastatic lesions.
Single agent maintenance therapy	Single agent	Maintenance treatment by single agent in a cycle of 21 days.

Primary Outcome Measures

Name	Time	Method
PFS	2 years	Progression-Free-Survival

Secondary Outcome Measures

Name	Time	Method
Abscopal effect rate	At the time point of 4 weeks after completion of rhGM-CSF	Radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field
OS	2 years	Overall survival

Trial Locations

Locations (2)

Shandong Cancer Hospital and Institute; 🇨🇳 Jinan, Shandong, China

SHANDONG Cancer Hospital; 🇨🇳 Jinan, Shandong, China