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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03989336
• Other study ID #: CHN-PLAGH-BT-040
• Status: Completed
• Phase: Phase 2
• Start date: December 23, 2020
• Est. completion date: December 10, 2023

Study information

• Verified date: February 2024
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: December 10, 2023
• Est. primary completion date: May 22, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Female.

3. = 18 years old.

4. Life expectancy of at least 6 months.

5. Eastern Cooperative Oncology Group performance status 0-2.

6. 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.

7. Subjects must have received at least two frontline therapies, at least one of which is platinum-containing.

8. Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.

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.

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Manganese Chloride
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
• nab-paclitaxel
Administered intravenously, 180-220mg/m2 on day 2 in a 3-week cycle (day 1 without Manganese priming)
• Platinum chemotherapy
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)
• Sintilimab
Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming)

Locations

Country	Name	City	State
China	Biotherapeutic Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24 months
Primary	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	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
Secondary	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.	12 months
Secondary	Overall survival (OS)	OS time was measured from the study entry to the date of death.	24 months
Secondary	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