Metastatic Solid TumorPRaG 2XNCT05435768
PraG With RANKL Inhibitor for the Treatment of Advanced Multiple Metastatic Solid Tumors
An observational study of Metastatic Solid Tumor, run by Second Affiliated Hospital of Soochow University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumor
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- How many people
- 51 participants
- Where
- 1 siteChina
- Study dates
- 16 Aug 2022to 15 Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Advanced solid tumors with multiple bone metastases
Who may be able to join
- 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
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site
The Second Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004
Yuehong Kong, Dr
Liyuan Zhang, Dr
About this study
Official title: PhaseⅠ-Ⅱ Clinical Study of Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF(PraG) With RANKL Inhibitor for the Treatment of Advanced Multiple Metastatic Solid Tumors
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.
Read the detailed description
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.
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.
The phase II study followed the treatment modality of the cohort with higher safety and efficacy assessments in the Phase I study and additional 39 patients were added.The primary endpoint is disease control rate. Secondary endpoints were objective response rate (ORR), median progression-free survival (PFS), overall survival (OS), and incidence of adverse events
- Conditions
- Metastatic Solid Tumor
- Being tested
- Denosumab
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Denosumab 120mg was subcutaneously administered one day before the commencement of radiotherapy or after the PraG treatment every 28 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does limiting toxicity（CTC 5.0）
Measured: phase 1 (1 year)
DCR
CR+PR+SD(RECIST 1.1)
Measured: phase 2 (18 months)
Secondary outcomes (5)
objective response rate
Measured: after 12-weeks treatment
progression-free survival
Measured: after 12-weeks treatment
overall survival
Measured: after 12-weeks treatment
incidence of skeletal related events
Measured: phase 1/2 (30 months)
toxic response
Measured: phase 2 (18 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2022
- Study start16 Aug 2022 (estimated)
- Primary completion15 Aug 2024 (estimated)
- Study completion15 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital of Soochow University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05435768
- Sponsor's protocol ID
- JD-LK-2022-035-01
- Acronym
- PRaG 2X
- Status last verified
- Aug 2022
- First submitted
- 12 Jun 2022
- Last updated
- 18 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33859942
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PhaseⅠ-Ⅱ Clinical Study of Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF(PraG) With RANKL Inhibitor for the Treatment of Advanced Multiple Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT05435768
- Acronym / sponsor ID
- PRaG 2X / JD-LK-2022-035-01
- Conditions
- Metastatic Solid Tumor
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 16 Aug 2022 (estimated)
- Primary completion
- 15 Aug 2024 (estimated)
- Study completion
- 15 Aug 2025 (estimated)
- First posted
- 28 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
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.
The phase II study followed the treatment modality of the cohort with higher safety and efficacy assessments in the Phase I study and additional 39 patients were added.The primary endpoint is disease control rate. Secondary endpoints were objective response rate (ORR), median progression-free survival (PFS), overall survival (OS), and incidence of adverse events
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A :RANKL inhibitor subsequently HFRT+GM-CSF+PD-1 inhibitor | – | Drug: DenosumabGroup 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. |
| Group B:HFRT+GM-CSF+PD-1 inhibitor subsequently RANKL inhibitor | – | Drug: DenosumabGroup 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Advanced solid tumors with multiple bone metastases
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabDenosumab 120mg was subcutaneously administered one day before the commencement of radiotherapy or after the PraG treatment every 28 days | Drug | Group A :RANKL inhibitor subsequently HFRT+GM-CSF+PD-1 inhibitor, Group B:HFRT+GM-CSF+PD-1 inhibitor subsequently RANKL inhibitor |
Primary outcome
Does limiting toxicity（CTC 5.0）
Time frame: phase 1 (1 year)
DCR
Time frame: phase 2 (18 months)
CR+PR+SD(RECIST 1.1)
5 secondary outcomes
objective response rate
Time frame: after 12-weeks treatment
progression-free survival
Time frame: after 12-weeks treatment
overall survival
Time frame: after 12-weeks treatment
incidence of skeletal related events
Time frame: phase 1/2 (30 months)
toxic response
Time frame: phase 2 (18 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Results publication: PubMed 33859942Kong 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Solid Tumor, run by Second Affiliated Hospital of Soochow University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yuehong Kong, Dr (13375183257, kkyuehong@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does limiting toxicity（CTC 5.0） (time frame: phase 1 (1 year)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05435768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2022.