SBRT in Multi-metastatic NSCLC Patients Which Are Pan-negative for Driver Mutations

NCT ID: NCT02940990

Last Updated: 2016-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Brief Summary

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This protocol is a phase II multi-center randomized controlled trial (RCT) evaluating the efficacy of SBRT in multi-metastatic NSCLC patients who are pan-negative for driver mutations.

Detailed Description

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Lung cancer is the leading cause of cancer death. Forty percent of patients are diagnosed as metastatic lung cancer, and about 50% of them are pan-negative for driver mutations. The median overall survival(OS) for these patients is 11 months, and maintenance therapy can only prolong 2 months of OS. The NCCN guidelines recommend 4-6 cycles of chemotherapy with or without maintenance chemotherapy.

Published data showed that radiotherapy modulates tumor phenotypes, enhances antigen presentation and tumor immunogenicity. The regression of out-field lesions was termed as "abscopal effect". The combination of radiotherapy with immunotherapeutic agents may promote the host anti-tumor immune response and increase the rate of abscopal effect.Published data showed that abscopal effect appeared in 20%-30% patients with metastatic malignant tumors who were treated with the combination of SBRT and GM-CSF.

The investigators evaluate the efficacy of the combination of SBRT and GM-CSF in the multi-metastatic NSCLC participants who are pan-negative for driver mutations. Patients enrolled will be randomized into two groups. The control group will receive the standard regimen as NCCN recommends. The experimental group will receive both the standard chemotherapy and the extra SBRT to primary lesions or metastatic lesions combined with GM-CSF. The investigators compare progress free survival(PFS) of the two groups.

Conditions

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NSCLC SBRT GM-CSF

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A

Participants in the Group A will receive 4-6 cycles of standard two-drug chemotherapy. After that, clinical observation or maintenance chemotherapy will be given.

Group Type PLACEBO_COMPARATOR

two-drug chemotherapy containing platinum, including carboplatin/Cisplatin + pemetrexed/docetaxel/paclitaxel/etoposide/gemcitabine/vinorelbine/albumin-bound paclitaxel

Intervention Type DRUG

two-drug regimen

Group B

Participants in the Group B will also receive 4-6 cycles of standard two-drug chemotherapy. However, they will receive an additional treatment of SBRT to primary lesions or metastatic lesions combined with GM-CSF.

Group Type EXPERIMENTAL

SBRT concurrent with GM-CSF

Intervention Type RADIATION

SBRT and GM-CSF 125ug/m2 for 14 days

two-drug chemotherapy containing platinum, including carboplatin/Cisplatin + pemetrexed/docetaxel/paclitaxel/etoposide/gemcitabine/vinorelbine/albumin-bound paclitaxel

Intervention Type DRUG

two-drug regimen

Interventions

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SBRT concurrent with GM-CSF

SBRT and GM-CSF 125ug/m2 for 14 days

Intervention Type RADIATION

two-drug chemotherapy containing platinum, including carboplatin/Cisplatin + pemetrexed/docetaxel/paclitaxel/etoposide/gemcitabine/vinorelbine/albumin-bound paclitaxel

two-drug regimen

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Histologically proven non-small-cell lung cancer.
* Stage IV according to UICC stage system(version 7,2009).The number of metastatic lesions\>5
* Pan-negative for driver mutations including EGFR ALK ROS1 c-MET
* At least Three evaluable lesions among which at least two must be suitable for SBRT.
* ECOG performance status 0-2.
* Expected lifespan ≥3 months.
* No brain metastasis in MRI.
* No liver metastasis in abdominal CT or MRI.
* No malignant pleural effusion or pericardial effusion from chest CT and/or pathology.
* Stable lab values: Hematological:

Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥9 g/dL Renal: Creatinine OR Measured or calculated creatinine clearance (CrCl) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) ≤1.5× the upper limit of normal (ULN) OR ≥60 mL/min for patient with creatinine levels \>1.5× institutional ULN Hepatic: Total bilirubin ≤1.5×ULN OR Direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5×ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN OR ≤5×ULN for patients with liver metastases ,globulin≥20 g/L, albumin≥30 g/L.

\- Able to understand and give written informed consent and comply with study procedures.

Exclusion Criteria

* Any unstable systemic disease, including active infection, uncontrolled high blood pressure, unstable angina, newly observed angina pectoris within the past 3 months, congestive heart failure (New York heart association (NYHA) class II or higher), myocardial infarction onset six months before included into the group, and severe arrhythmia, liver, kidney, or metabolic disease in need of drug therapy.
* Previously diagnosed with immunodeficiency disease.
* Human immunodeficiency virus (HIV) infection.
* Women in pregnancy or lactation .
* Patients with mental illness, considered as "can't fully understand the issues of this research".
* other Cancer history.
* Histologically confirmed small cell carcinoma or other non NSCLC compositions in the cancer tissue.
* Brain metastasis or liver metastasis or malignant pleural effusion or pericardial effusion.
* Allergy of rhGM-CSF and its accessories.
* Contraindications to GM-CSF treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Chest Hospital

OTHER

Sponsor Role lead

Responsible Party

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Xiaolong Fu

Director, Department of Radiation Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

Facility Contacts

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Xiaolong Fu, PhD

Role: primary

References

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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.

Reference Type RESULT
PMID: 26095785 (View on PubMed)

Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8.

Reference Type RESULT
PMID: 26951040 (View on PubMed)

Stamell EF, Wolchok JD, Gnjatic S, Lee NY, Brownell I. The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):293-5. doi: 10.1016/j.ijrobp.2012.03.017. Epub 2012 May 5.

Reference Type RESULT
PMID: 22560555 (View on PubMed)

Daly ME, Monjazeb AM, Kelly K. Clinical Trials Integrating Immunotherapy and Radiation for Non-Small-Cell Lung Cancer. J Thorac Oncol. 2015 Dec;10(12):1685-93. doi: 10.1097/JTO.0000000000000686.

Reference Type RESULT
PMID: 26484629 (View on PubMed)

Abuodeh Y, Venkat P, Kim S. Systematic review of case reports on the abscopal effect. Curr Probl Cancer. 2016 Jan-Feb;40(1):25-37. doi: 10.1016/j.currproblcancer.2015.10.001. Epub 2015 Oct 9.

Reference Type RESULT
PMID: 26582738 (View on PubMed)

Other Identifiers

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SCHLC007

Identifier Type: -

Identifier Source: org_study_id