Efficacy and Safety of HGXJT in Bone Metastatic NSCLC Patients

Official title

Efficacy and Safety of Bone-protecting and Mass-dispersesing Decoction (HuGuXiaoJiTang, HGXJT) Combining With ICIs in Bone Metastatic NSCLC Patients

Overview

This is a double-blind, randomized controlled study evaluating the efficacy and safety of HGXJT in combination with ICI-based standard treatment in lung cancer patients with bone metastases. Enrolled participates will randomly receive HGXJT or placebo during the first 4-6 cycles of ICI-based standard treatment.

Interventions

• Drug ICI
  PD-1 inhibitors selected by clinicians based on patients' condition
• Drug Chemotherapy
  AP regimen（Pemetrexed 500mg/m2+carboplatin AUC=5,q3w） for non-squamous cancer patientsor or TP regimen（Paclitaxel 175mg/m2+carboplatin AUC=5, or albumin paclitaxel 100mg/m2+carboplatin AUC=5,q3w）for Squamous cancer patients.
• Drug Placebo
  The particle size and color are similar to the HGXJT, and the smell and taste are close to the HGXJT, and the bacteria test is qualified
• Drug Bone-protecting and Mass-dispersesing Decoction
  Chinese Herbal Formula,also named as HGXJT

Primary outcome measures

• (Disease control rate assessed by investigators) DCR (CR+PR+SD) [Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.]

Secondary outcome measures (3)

• Progression-free survival (PFS) [Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.]
• Overall survival (OS) [Time frame: From date of randomization to the date of withdraw or date of death from any cause, whichever occurs first, assessed up to 120 months.]
• ORR(Objective response rate) [Time frame: From date of randomization until the date of death or date of withdraw, whichever came first, assessed up to 120 months]

Eligibility criteria

Inclusion criteria

• Patients with non-small cell lung cancer diagnosed by histopathology or cytopathology.
• Presence of bone metastases.
• EGFR/ALK gene wild type.
• No prior treatment with PD-1 inhibitors (combination or monotherapy)
• Those who have not received prior antitumor therapy or have not received further antitumor therapy after failure of first-line antitumor therapy.
• PS score (ECOG) ≤ 2 points
• Normal hepatic and renal function.

Normal hepatic function: total serum bilirubin level ≤ 1.5 times of the upper limit of normal value(ULN), serum serum aspartate aminotransferase(AST) \& alanine aminotransferase(ALT) ≤ 2.5 times ULN

Normal renal function: serum creatinine ≤ 1.5 mg/dl (133 μmol/L) and/or creatinine clearance ≥ 60 ml/min.

• Presence of at least one assessable lesion.
• Signed informed consent, patient willing to accept this regimen, able to adhere to the medication, and good compliance.

Exclusion criteria

• Unable to complete the baseline assessment form
• Combination of other serious illnesses, including uncontrolled active infection, severe electrolyte disturbances, and significant bleeding tendencies.
• Pregnant or lactating women.
• Combined autoimmune diseases, hematologic disorders, or long-term use of hormones or immunosuppressive drugs.
• Combination of other uncontrolled tumors.
• Combination of severe brain or mental illness that affects the patient's ability to self-report.
• Combined organ transplant history (including bone marrow autotransplantation and peripheral stem cell transplantation).
• Those who are legally incompetent and whose medical or ethical reasons affect the continuation of the research.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Guangdong Provincial Hospital of Traditional Chinese Medicine — Guangzhou

Publications

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Proto C, Lo Russo G, Corrao G, Ganzinelli M, Facchinetti F, Minari R, Tiseo M, Garassino MC. Treatment in EGFR-mutated non-small cell lung cancer: how to block the receptor and overcome resistance mechanisms. Tumori. 2017 Jul 31;103(4):325-337. doi: 10.5301/tj.5000663. Epub 2017 Jul 1. PMID 28708233
• Zhong WZ, Zhou Q, Wu YL. The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer. Oncotarget. 2017 Aug 17;8(41):71358-71370. doi: 10.18632/oncotarget.20311. eCollection 2017 Sep 19. PMID 29050366
• Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-Line Nivolumab PMID 28636851
• Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Sma PMID 29658856
• Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Felip E, Goldman JW, Scalzo C, Jensen E, Kush DA, Hui R. Five-Year Overall Survival for Patients With Advanced Non-Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019 Oct 1;37(28):2518-2527. PMID 31154919
• Remon J, Passiglia F, Ahn MJ, Barlesi F, Forde PM, Garon EB, Gettinger S, Goldberg SB, Herbst RS, Horn L, Kubota K, Lu S, Mezquita L, Paz-Ares L, Popat S, Schalper KA, Skoulidis F, Reck M, Adjei AA, Scagliotti GV. Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations. J Thorac Oncol. 2020 Jun;15(6):914-947. doi: 10.1016/ PMID 32179179
• Chen Xian, Zhang Haibo, Liu Yihong, et al. Study on the correlation between the efficacy and NTX level of bone metastasis cancer pain treated with Bone Protecting and Anti-accumulation Formula combined with zoledronic acid and the evidence of kidney deficiency in Chinese medicine. New Chinese Medicine, 2017, 49(10): 117-120.

Identifiers

NCT: NCT05378334 · 2021KT0613

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗