A Study of the Pan-immunotherapy in Patients With Relapsed/Refractory Ovarian Cancer

NCT03989336 | Completed Phase 2 DMC

• 1 other identifier: CHN-PLAGH-BT-040
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Disease control rate (DCR)

  12 months

• Progression-free survival (PFS)

  12 months

• Overall survival (OS)

  24 months

• Number of participants with laboratory test abnormalities

  12 months

Study Arms (2)

Manganese primed Sintilimab plus nPP chemotherapy

EXPERIMENTAL

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.

Drug: Manganese Chloride; Drug: nab-paclitaxel; Drug: Platinum chemotherapy; Drug: Sintilimab

Sintilimab plus nPP chemotherapy

ACTIVE COMPARATOR

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.

Drug: nab-paclitaxel; Drug: Platinum chemotherapy; Drug: Sintilimab

Interventions

Manganese Chloride DRUG

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

Manganese primed Sintilimab plus nPP chemotherapy

nab-paclitaxel DRUG

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

Also known as: Paclitaxel For Injection (Albumin Bound)

Manganese primed Sintilimab plus nPP chemotherapy; Sintilimab plus nPP chemotherapy

Platinum chemotherapy DRUG

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)

Manganese primed Sintilimab plus nPP chemotherapy; Sintilimab plus nPP chemotherapy

Sintilimab DRUG

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

Also known as: anti-PD-1 antibody; PD-1 inhibitor

Manganese primed Sintilimab plus nPP chemotherapy; Sintilimab plus nPP chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence

Interventions

manganese chloride; 130-nm albumin-bound paclitaxel; Paclitaxel; Injections; sintilimab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Drug Administration Routes; Drug Therapy; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 15, 2019
• First Posted: June 18, 2019
• Study Start: December 23, 2020
• Primary Completion: May 22, 2022
• Study Completion: December 10, 2023
• Last Updated: July 15, 2024

Record last verified: 2024-07

Locations

CN (1)