PraG With RANKL Inhibitor for the Treatment of Advanced Multiple Metastatic Solid Tumors

NCT05435768 | Unknown

• 1 other identifier: JD-LK-2022-035-01
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The PraG treatment model has synergistic effects with RANKL inhibitor therapy, and the combination of the two treatments provides a survival benefit for patients with multiple bone metastatic solid tumors who have failed first-line systemic therapy. Phase I clinical trial is planned to determine the safety of PraG treatment mode combined with RANKL inhibitor desomumab and the optimal treatment sequence and mode. Further phase II clinical trial was conducted to confirm the efficacy of PraG treatment combined with desomumab. The mechanism of combination therapy was analyzed and biomolecular markers for potential efficacy prediction were screened by detection of lymphocyte subsets, cytokines and metabolomics in peripheral blood.

Conditions

Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Does limiting toxicity（CTC 5.0）

  phase 1 (1 year)

• DCR

  CR+PR+SD(RECIST 1.1)

  phase 2 (18 months)

Secondary Outcomes (5)

• objective response rate

  after 12-weeks treatment

• progression-free survival

  after 12-weeks treatment

• overall survival

  after 12-weeks treatment

• incidence of skeletal related events

  phase 1/2 (30 months)

• toxic response

  phase 2 (18 months)

Study Arms (2)

Group A :RANKL inhibitor subsequently HFRT+GM-CSF+PD-1 inhibitor

Group A(6 patients):patients were subcutaneously injected with 120mg desomumab, and on the second day after injection, the metastatic lesions were treated with hypofractioniated radiotherapy (8Gy×3F or 5Gy×3F), and subcutaneously injected with GM-CSF(200 μg/d) for 7 days, followed by IL-2 (2 million IU/d) for 7 days,and a 200mg PD-1 inhibitor administered within one week after completion of radiotherapy. The course was repeated every 28 days for 2-4 cycles.After combination therapy, maintenance therapy with PD-1inhibitor and desomumab was administered until disease progression or unacceptable toxicity.

Drug: Denosumab

Group B:HFRT+GM-CSF+PD-1 inhibitor subsequently RANKL inhibitor

Group B(6 patients):patients were treated with hypofractioniated radiotherapy (8Gy×3F or 5Gy×3F), and subcutaneously injected with GM-CSF(200 μg/d) for 7 days, followed by IL-2 (2 million IU/d) for 7 days.On the second day after radiotherapy, 200mg pd-1 inhibitor was administered. After treatment, 120mg desomumab was subcutaneously injected. The course was repeated every 28 days for 2-4 cycles.After combination therapy, maintenance therapy with PD-1inhibitor and desomumab was administered until disease progression or unacceptable toxicity.

Drug: Denosumab

Interventions

Denosumab DRUG

Denosumab 120mg was subcutaneously administered one day before the commencement of radiotherapy or after the PraG treatment every 28 days

Group A :RANKL inhibitor subsequently HFRT+GM-CSF+PD-1 inhibitor; Group B:HFRT+GM-CSF+PD-1 inhibitor subsequently RANKL inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Advanced solid tumors with multiple bone metastases

You may qualify if:

• Aged≥18 years
• The patients must conform to the advanced solid cancer with multiple metastases(may be accompanied by metastasis of other organs),progression after first-line systemic therapy and have clear pathological diagnosis report
• The hematopoietic function and general condition of the patients were acceptable(white blood cells \>2.5×10\^9/L,lymphocyte\>0.5 times of normal lower limit，Platelets\>50×10\^9/L）
• There was no history of serious hematopoietic function, abnormal heart, lung, liver, kidney function and immune deficiency
• One week before enrollment,absolute value of T lymphocytes≥0.5 times of normal lower limit，neutrophil ≥ 1.0×109/L，AST and ALT ≤3.0 times normal upper limit(Liver cancer/liver metastasis patients ≤5.0 times normal upper limit);creatinine ≤ 3.0 times normal upper limit;serum calcium≥2.0mmol/L
• Patients's activity status was assessed by Eastern Cooperative Oncology Group(ECOG) score of 0-3,and life expectancy of more than 3 months
• Abide by the plan during the study period
• Sign written consent

You may not qualify if:

• Pregnant or lactating women
• Patinets diagnosed with other malignant disease in the past five years,except for cured skin cancer and cervical carcinoma in situ
• The clinical severity of uncontrolled epilepsy,central nervous system disease or mental disorder may hinder the signing of informed consent or affect the patient's compliance with medication
• Sever(i.e. active)heart disease,such an symptomatic coronary heart disease,New York Heart Association(NYHA) class Ⅱ or more severe congestive heart failure or severe arrhythmia requiring drug intervention,or a history of myocardial infraction in the last 12 months；
• Organ transplantation require immunosuppressive therapy
• Major active infections are known,or other serious uncontrolled concomitant diseases;endocrine or metabolic disorders,or other serious uncontrolled concomitant diseases;
• The baseline blood routine did not meet the following criteria:hemoglobin≥90g/L;absolute neutrophil count(ANC)≥1.5×109/L;platelet≥50×109/L;ALT,AST≤2.5 times normal upper limit value;ALP≤2.5 times normal upper limit value; serum total bilirubin\<1.5 times normal upper limit value;Serum creatinine \<3 times normal upper limit value;serum albumin≥30g/L;
• Anaphylaxis to any research drug ingredients
• Patients with a history of immunodeficiency,including HIV postive or with other acquired or congenital immunodeficiency disorders,or with a history of organ transplantation,or with other immune-related diseases requiring long-term oral hormone therapy
• In the period of acute and chronic tuberculosis infection (T-spot test positive,chest X-ray suspicious tuberculosis focus patients)
• Researchers considered that it was not suitable for other situations in the group

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead

Study Sites (1)

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

Location

Related Publications (1)

• Kong Y, Ma Y, Zhao X, Pan J, Xu Z, Zhang L. Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers. Front Oncol. 2021 Mar 30;11:638873. doi: 10.3389/fonc.2021.638873. eCollection 2021.

  PMID: 33859942 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yuehong Kong, Dr

CONTACT

13375183257; kkyuehong@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2022
• First Posted: June 28, 2022
• Study Start: August 16, 2022
• Primary Completion: August 15, 2024
• Study Completion: August 15, 2025
• Last Updated: August 18, 2022

Record last verified: 2022-08

Locations

CN (1)