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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Solid Tumor
• Intervention / Treatment: Drug: Manganese Chloride; Radiation: Radiotherapy; Drug: Chemo-immunotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weidong Han, M.D.; Phone Number: +861066937463; Email: hanwdrsw69@yahoo.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital
      • Contact: Weidong D Han, M.D.; Phone Number: +86-10-66937463; Email: hanwdrsw69@yahoo.com
      • Sub-Investigator: Fengxia Shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Manganese plus 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.

Drug: Manganese Chloride; Administered by inhalation at 0.4mg/kg/d twice a week; Other Names: Mn2+; Radiation: Radiotherapy; Measurable lesions were targeted for radiotherapy at the discretion of the treating physician.Standard-of-care radiotherapy or SBRT were both allowed.; Drug: Chemo-immunotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
Overall survival (OS)	OS time was measured from the study entry to the date of death.	24 months
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.	24 months
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.	12 months

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 6, 2021
• Primary Completion (Anticipated): May 31, 2022
• Study Completion (Anticipated): May 31, 2023

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: radiotherapy; metastatic; abscopal response; manganese
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Trace Elements; Micronutrients; Manganese
• Other Study ID Numbers: CHN-PLAGH-BT-063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No