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An Open-label, Phase I/II Study of the Pan-immunotherapy in Patients With Relapsed/Refractory Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Manganese Chloride

nab-paclitaxel

Platinum chemotherapy

Sintilimab

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring relapsed, refractory, anti-PD-1 antibody, Manganese, chemotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must have histologically proven relapsed or refractory ovarian cancer (Refractory was defined as a lack of response to or progression during the frontline treatment; relapsed was defined as progression after the frontline treatment), including patients diagnosed with primary carcinoma of fallopian tube or peritoneum carcinoma.
Female.
≥ 18 years old.
Life expectancy of at least 6 months.
Eastern Cooperative Oncology Group performance status 0-2.
Radiographic imaging (CT/MRI/PET-CT) indicated recurrence or metastasis; or cancer cells in ascites are positive; or CA125 concentration in the peripheral blood is more than 2 times the upper limit of normal value.
Subjects must have received at least two frontline therapies, at least one of which is platinum-containing.
Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
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.

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 2

Arm Type

Experimental

Active Comparator

Arm Label

Manganese primed Sintilimab plus nPP chemotherapy

Sintilimab plus nPP chemotherapy

Arm Description

Subject received Manganese primed Sintilimab, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent.

Subject received Sintilimab, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent.

Outcomes

Primary Outcome Measures

Object response rate (ORR)

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

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

NCT03989336

First Posted

June 15, 2019

Last Updated

December 20, 2020

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03989336

Brief Title

An Open-label, Phase I/II Study of the Pan-immunotherapy in Patients With Relapsed/Refractory Ovarian Cancer

Official Title

A Phase I/II, Open-label, Two-arm, Single-center Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Relapsed/Refractory Ovarian Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 20, 2019 (Actual)

Primary Completion Date

May 31, 2021 (Anticipated)

Study Completion Date

October 30, 2022 (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

Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Platinum chemotherapy has been widely adopted as a standard treatment for advanced ovarian cancer, the response rates in patients with relapsed/refractory ovarian cancer is unacceptably low. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This two-arm, phase I/II study is designed to assess the safety and efficacy of combined therapy of anti-PD-1 antibody and chemotherapy with or without Manganese priming.

6. Conditions and Keywords

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

Ovarian Cancer

Keywords

relapsed, refractory, anti-PD-1 antibody, Manganese, chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Manganese primed Sintilimab plus nPP chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Sintilimab plus nPP chemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Manganese Chloride

Intervention Description

Administered by inhalation at 0.4mg/kg twice per week in the first 3-week cycle, and then inhaled 0.4mg/kg twice in the first week of each 3-week cycle thereafter

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

Paclitaxel For Injection (Albumin Bound)

Intervention Description

Administered intravenously, 180-220mg/m2 on day 2 in a 3-week cycle (day 1 without Manganese priming)

Intervention Type

Drug

Intervention Name(s)

Platinum chemotherapy

Intervention Description

Administered intravenously, Cisplatin (60-80mg/m2) or Carboplatin (area under the curve [AUC] 4-6 mg/mL per min) on day 2 in a 3-week cycle (day 1 without Manganese priming)

Intervention Type

Drug

Intervention Name(s)

Sintilimab

Other Intervention Name(s)

anti-PD-1 antibody; PD-1 inhibitor

Intervention Description

Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming)

Primary Outcome Measure Information:

Title

Object response rate (ORR)

Description

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

Time Frame

24 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

12 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

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must have histologically proven relapsed or refractory ovarian cancer (Refractory was defined as a lack of response to or progression during the frontline treatment; relapsed was defined as progression after the frontline treatment), including patients diagnosed with primary carcinoma of fallopian tube or peritoneum carcinoma. Female. ≥ 18 years old. Life expectancy of at least 6 months. Eastern Cooperative Oncology Group performance status 0-2. Radiographic imaging (CT/MRI/PET-CT) indicated recurrence or metastasis; or cancer cells in ascites are positive; or CA125 concentration in the peripheral blood is more than 2 times the upper limit of normal value. Subjects must have received at least two frontline therapies, at least one of which is platinum-containing. Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance. 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. 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

Phone

01066937463

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: