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An Open-label, Phase I/II Study of Manganese Plus Radiotherapy in Patients With Metastatic Solid Tumors or Lymphoma

Primary Purpose

Solid Tumor, Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Manganese Chloride

Radiotherapy

Chemo-immunotherapy

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring metastatic, radiotherapy, manganese, abscopal response

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must have histologically proven metastatic solid tumors or lymphoma.
Subjects must have at least two distinct measurable sites of disease (≥1 cm).
≥ 18 years old.
Life expectancy of at least 6 months.
Eastern Cooperative Oncology Group performance status 0-2.
Subjects must have stable or progressing disease to the ongoing systemic therapy.
Multiple lines of previous chemo-immunotherapy were permitted.
Patients with known brain metastases were included in the trial but brain lesions were not eligible as target or non-target lesions.
Adequate organ function.
Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria:

Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
Prior organ allograft.
Women who are pregnant or breastfeeding.
Women with a positive pregnancy test on enrollment or prior to investigational product administration.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Subjects with previous or concurrent other malignancies.

Sites / Locations

Biotherapeutic Department of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Manganese plus Radiotherapy

Arm Description

Subject received standard-of-care radiotherapy or stereotactic body radiation therapy (SBRT) to one metastatic site. Manganese inhalation began 1 week after the start of radiotherapy and lasted up to 6 months. The same systemic therapy before the enrollment will be maintained.

Outcomes

Primary Outcome Measures

Proportion of subjects with an abscopal response

An abscopal response was defi ned as a decrease in the longest diameter of at least 30% in any measurable (≥1 cm) non-irradiated lesion from baseline.

Number of subjects with treatment-related adverse events (AEs)

Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.

Secondary Outcome Measures

Disease control rate (DCR)

DCR is defined as the proportion of subjects who achieved a stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Progression-free survival (PFS)

PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1.

Overall survival (OS)

OS time was measured from the study entry to the date of death.

Number of participants with laboratory test abnormalities

The laboratory tests of serum cytokines and chemokines will be performed on day 1 and 3 of each cycle, and the abnormality will be determined by the investigator.

Full Information

NCT ID

NCT04873440

First Posted

April 30, 2021

Last Updated

May 4, 2021

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04873440

Brief Title

An Open-label, Phase I/II Study of Manganese Plus Radiotherapy in Patients With Metastatic Solid Tumors or Lymphoma

Official Title

A Phase I/II, Open-label Study to Evaluate the Abscopal Response and Safety of Manganese and Standard-of-care Radiotherapy/ SBRT in Subjects With Metastatic Solid Tumors or Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

May 6, 2021 (Anticipated)

Primary Completion Date

May 31, 2022 (Anticipated)

Study Completion Date

May 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Radiotherapy is a regular care for metastatic solid tumors or lymphoma, and it can induce immunogenic death of tumor cells and a stronger immune response. Sometimes, tumor regression would be observed at sites distant to an irradiated field because of the radiotherapy-induced anticancer immune responses, so-called abscopal response. Manganese has been confirmed to activate innate immune and function as anticancer immunoadjuvant in pre-clinical studies. This study is designed to assess the abscopal response and safety of combined therapy of manganese and radiotherapy in patients with metastatic solid tumors or lymphoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumor, Lymphoma

Keywords

metastatic, radiotherapy, manganese, abscopal response

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Manganese plus Radiotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Manganese Chloride

Other Intervention Name(s)

Mn2+

Intervention Description

Administered by inhalation at 0.4mg/kg/d twice a week

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

Measurable lesions were targeted for radiotherapy at the discretion of the treating physician.Standard-of-care radiotherapy or SBRT were both allowed.

Intervention Type

Drug

Intervention Name(s)

Chemo-immunotherapy

Intervention Description

The same chemotherapy and/or anti-PD-1 therapy before thei patients' enrolment were allowed. Whether and which should be given depends on the treatment regimen before enrollment.

Primary Outcome Measure Information:

Title

Proportion of subjects with an abscopal response

Description

An abscopal response was defi ned as a decrease in the longest diameter of at least 30% in any measurable (≥1 cm) non-irradiated lesion from baseline.

Time Frame

6 months

Title

Number of subjects with treatment-related adverse events (AEs)

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Disease control rate (DCR)

Description

Time Frame

12 months

Title

Progression-free survival (PFS)

Description

PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1.

Time Frame

24 months

Title

Overall survival (OS)

Description

OS time was measured from the study entry to the date of death.

Time Frame

24 months

Title

Number of participants with laboratory test abnormalities

Description

The laboratory tests of serum cytokines and chemokines will be performed on day 1 and 3 of each cycle, and the abnormality will be determined by the investigator.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must have histologically proven metastatic solid tumors or lymphoma. Subjects must have at least two distinct measurable sites of disease (≥1 cm). ≥ 18 years old. Life expectancy of at least 6 months. Eastern Cooperative Oncology Group performance status 0-2. Subjects must have stable or progressing disease to the ongoing systemic therapy. Multiple lines of previous chemo-immunotherapy were permitted. Patients with known brain metastases were included in the trial but brain lesions were not eligible as target or non-target lesions. Adequate organ function. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug. Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug. Exclusion Criteria: Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications. Serious uncontrolled medical disorders or active infections, pulmonary infection especially. Prior organ allograft. Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to investigational product administration. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. Subjects with previous or concurrent other malignancies.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Weidong Han, M.D.

Phone

+861066937463

hanwdrsw69@yahoo.com

Facility Information:

Facility Name

Biotherapeutic Department of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact: