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

Phase 1

• Conditions: Lymphoma; Solid Tumor
• Interventions: Drug: Manganese Chloride; Radiation: Radiotherapy; Drug: Chemo-immunotherapy

• Registration Number: NCT04873440
• Lead Sponsor: Chinese PLA General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-30
• Status Verified: 2021-05
• Study First Submitted QC: 2021-05-04
• Last Update Submitted: 2021-05-04
• Study First Posted: 2021-05-05
• Last Update Posted: 2021-05-05
• Study Start: 2021-05-06
• Primary Completion: 2022-05-31
• Study Completion: 2023-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Subjects must have histologically proven metastatic solid tumors or lymphoma.
2. Subjects must have at least two distinct measurable sites of disease (≥1 cm).
3. ≥ 18 years old.
4. Life expectancy of at least 6 months.
5. Eastern Cooperative Oncology Group performance status 0-2.
6. Subjects must have stable or progressing disease to the ongoing systemic therapy.
7. Multiple lines of previous chemo-immunotherapy were permitted.
8. Patients with known brain metastases were included in the trial but brain lesions were not eligible as target or non-target lesions.
9. Adequate organ function.
10. 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.
11. 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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Manganese plus Radiotherapy	Radiotherapy	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.
Manganese plus Radiotherapy	Chemo-immunotherapy	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.
Manganese plus Radiotherapy	Manganese Chloride	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.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with an abscopal response	6 months	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)	12 months	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

Name	Time	Method
Overall survival (OS)	24 months	OS time was measured from the study entry to the date of death.
Number of participants with laboratory test abnormalities	12 months	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.
Disease control rate (DCR)	12 months	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)	24 months	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.

Trial Locations

Locations (1)

Biotherapeutic Department of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China