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

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

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Pemetrexed; Biological: rhGM-CSF; Radiation: Local Radiotherapy; Drug: Single agent

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 Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ming Huan Li, doctor; Phone Number: 131 5303 5389; Email: sy_lmh2001@163.com
• Study Contact Backup: Name: JINMING YU, doctor; Phone Number: 0531-87984729 13806406293; Email: jn7984729@public.jn.sd.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Cancer Hospital
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Cancer Hospital and Institute
      • Contact: MINGHUAN LI, Doctor; Phone Number: 0531-67626112 13153035389; Email: Sy_lmh2001@163.com
      • Contact: JIMING YU, Doctor; Phone Number: 0531-87984729 13806406293; Email: jn7984729@public.jn.sd.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy+chemotherapy+ 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.	Drug: Pemetrexed; Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer.; Biological: rhGM-CSF; rhGM-CSF is a stimulator of the growth and differentiation of hematopoietic progenitor cells committed to neutrophils, monocytes or eosinophils. rhGM-CSF can promote the maturation of dendritic cells and macrophage, increase their antigen presentation ability.; Other Names: Recombinant human granulocyte macrophage stimulating factor; Radiation: Local Radiotherapy; Radiotherapy promotes the release of tumor antigen; Other Names: Local Radiation therapy; Drug: Single agent; Other chemotherapy drugs,such as Docetaxel, gemcitabine; Other Names: Single agent for maintenance therapy
Experimental: Single agent maintenance therapy; Maintenance treatment by single agent in a cycle of 21 days.	Drug: Single agent; Other chemotherapy drugs,such as Docetaxel, gemcitabine; Other Names: Single agent for maintenance therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-Free-Survival	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: JINMING YU, doctor, Shandong Cancer Hospital and Institute

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: SDCH201701LC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No