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A Safety Study of the Pan-immunotherapy in Patients With Unresectable/Metastatic Solid Tumors or Lymphomas

Primary Purpose

Solid Tumor, Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Manganese Chloride

Anti-PD-1 antibody

Systemic therapy

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring anti-PD-1 antibody, Manganese, unresectable, metastatic

Eligibility Criteria

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

Inclusion Criteria:

Subjects must have histologically proven unresectable/ metastatic solid tumors or lymphomas.
≥ 18 years old.
Life expectancy of at least 6 months.
Eastern Cooperative Oncology Group performance status 0-2.
Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
Subjects must have received at least two frontline therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.
Subjects must be off prior therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
Adequate organ function.
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.

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.
T cell lymphomas or leukemia.
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.

Sites / Locations

Biotherapeutic Department of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Dose-Escalation, intranasally

Dose-Escalation, inhalation

Arm Description

With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached.

With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached.

Outcomes

Primary Outcome Measures

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.

Number of subjects with specific Manganese-related adverse events

Manganese-related AEs were considered to be that start or worsen after administration Manganese administration，improve after withdrawal, and even occur again after re-administration.

Secondary Outcome Measures

Preliminary efficacy evaluation

Objective response rate (ORR) and disease control rate (DCR) will be evaluated by investigators per the RECIST V1.1.

The q3w pharmacokinetic profile of Manganese

PK parameters such as Maximum concentration (Cmax) are assessed.

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

NCT03991559

First Posted

June 14, 2019

Last Updated

August 27, 2019

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03991559

Brief Title

A Safety Study of the Pan-immunotherapy in Patients With Unresectable/Metastatic Solid Tumors or Lymphomas

Official Title

A Phase I, Two-arm, Open-label, Single-center, Dose-escalation Study to Evaluate the Safety, Tolerability and Recommended Dose and Delivery Mode of the Pan-immunotherapy in Subjects With Unresectable/ Metastatic Solid Tumors or Lymphomas

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Unknown status

Study Start Date

November 1, 2018 (Actual)

Primary Completion Date

December 31, 2019 (Anticipated)

Study Completion Date

May 31, 2020 (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

Identification of T cell inhibitory signals, including PD-1/PD-L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I, 3 + 3 dose escalation study of a combined regimen of Manganese and anti-PD-1 antibody with or without chemotherapies in subjects with unresectable/ metastatic solid tumors or lymphomas. This study is designed to assess the safety, tolerability, pharmacokinetic profile (PK profile), mode of delivery and Recommended Phase 2 Dose (RP2D) of this regimen.

6. Conditions and Keywords

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

Solid Tumor, Lymphoma

Keywords

anti-PD-1 antibody, Manganese, unresectable, metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose-Escalation, intranasally

Arm Type

Active Comparator

Arm Description

With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached.

Arm Title

Dose-Escalation, inhalation

Arm Type

Active Comparator

Arm Description

With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached.

Intervention Type

Drug

Intervention Name(s)

Manganese Chloride

Intervention Description

Administered intranasally in Arm 1 (0.05, 0.1 or 0.2 mg/kg/d) and by inhalation in Arm 2 (0.1, 0.2 or 0.4mg/kg/d) once daily in a 3-week cycle

Intervention Type

Drug

Intervention Name(s)

Anti-PD-1 antibody

Other Intervention Name(s)

Anti-PD-1 monoclonal antibody, PD-1 inhibitor

Intervention Description

Administered intravenously, at 2-4mg/kg on day 3 in a 3-week cycle

Intervention Type

Combination Product

Intervention Name(s)

Systemic therapy

Intervention Description

Whether and which should be given depends on the treatment regimen before enrollment.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Approximately 6 months

Title

Number of subjects with specific Manganese-related adverse events

Description

Manganese-related AEs were considered to be that start or worsen after administration Manganese administration，improve after withdrawal, and even occur again after re-administration.

Time Frame

Approximately 6 months

Secondary Outcome Measure Information:

Title

Preliminary efficacy evaluation

Description

Objective response rate (ORR) and disease control rate (DCR) will be evaluated by investigators per the RECIST V1.1.

Time Frame

Approximately 6 months

Title

The q3w pharmacokinetic profile of Manganese

Description

PK parameters such as Maximum concentration (Cmax) are assessed.

Time Frame

Approximately 3 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

Approximately 3 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 unresectable/ metastatic solid tumors or lymphomas. ≥ 18 years old. Life expectancy of at least 6 months. Eastern Cooperative Oncology Group performance status 0-2. Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria. Subjects must have received at least two frontline therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma. Subjects must be off prior therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance. Adequate organ function. 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. 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. T cell lymphomas or leukemia. 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.

Central Contact Person:

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

Weidong Han, M.D.

Phone

+861066937463

hanwdrsw@sina.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: