Safety and Efficacy of Toripalimab in HER2- Metastatic Breast Cancer Patients Treated With Metronomic Vinorelbine

NCT04389073 | Unknown Phase 2

• 1 other identifier: NCC2167
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators hypothesize that the administration of Toripalimab (anti-PD-1 antibody, JS001) combined to metronomic Vinorelbine may be an interesting therapeutic option for female patients with HER2- metastatic breast cancer. The approach suggested here is to deplete and active the immune response of these patients. The combination of Toripalimab and Vinorelbine would provide a higher gain in anti-tumor response in these patients than in those with chemotherapy alone. The investigators proposal is to conduct a multicentric, single arm, Phase II trial in HER2- patients with metastatic breast cancer, aiming to evaluate the clinical activity of the combination therapy Toripalimab + metronomic Vinorelbine. Patients will receive Vinorelbine (40 mg/day, tiw, per os) and Toripalimab (240 mg every 3 weeks, intravenously \[IV\]). The adverse events of the two drugs are well known.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  CBR, defined as the percentage of Complete Response (CR), (Partial Response) PR or Stable Disease (SD) . Response will be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1.

  6 weeks of treatment

Secondary Outcomes (4)

• Overall response Rate (ORR)

  6 weeks of treatment

• Progression-Free Survival (PFS)

  15 months

• Overall Survival (OS)

  15 months

• Adverse events reporting

  15 months

Study Arms (5)

Arm 1 (PD-1+NVB)

EXPERIMENTAL

The treatments received are: * Vinorelbine (40 mg/day, tiw, per os) * Toripalimab (240 mg every 3 weeks, intravenously \[IV\]).

Drug: Vinorelbine 40mg; Biological: Toripalimab 240mg

Arm 2 (PD-1+NVB+Bev)

EXPERIMENTAL

The treatments received are: * Vinorelbine (40 mg/day, tiw, per os) * Toripalimab (240 mg every 3 weeks, intravenously \[IV\]) * Bevacizumab (5 mg/kg every 3 weeks, intravenously \[IV\]).

Drug: Vinorelbine 40mg; Biological: Toripalimab 240mg; Biological: Bevacizumab 5 mg/kg

Arm 3 (PD-1+NVB+DDP)

EXPERIMENTAL

* Vinorelbine (40 mg/day, tiw, per os) * Toripalimab (240 mg every 3 weeks, intravenously \[IV\]) * Cisplatin (50mg/m2 every 3 weeks, intravenously \[IV\]).

Drug: Vinorelbine 40mg; Biological: Toripalimab 240mg; Drug: Cisplatin

Arm 4 (PD-1+VEX)

EXPERIMENTAL

* Vinorelbine (40 mg/day, tiw, per os) * Toripalimab (240 mg every 3 weeks, intravenously \[IV\]) * Cyclophosphamide (50 mg/day, qd, per os) * Capecitabine (500 mg, tid, per os)

Drug: Vinorelbine 40mg; Biological: Toripalimab 240mg; Drug: Cyclophosphamide 50 mg; Drug: Capecitabine 500Mg Oral Tablet

Arm 5 (NVB)

ACTIVE COMPARATOR

• Vinorelbine (40 mg/day, tiw, per os)

Drug: Vinorelbine 40mg

Interventions

Vinorelbine 40mg DRUG

Two tablets per day, three times a week. Vinorelbine will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Arm 1 (PD-1+NVB); Arm 2 (PD-1+NVB+Bev); Arm 3 (PD-1+NVB+DDP); Arm 4 (PD-1+VEX); Arm 5 (NVB)

Toripalimab 240mg BIOLOGICAL

Toripalimab 240 MG IV infusion every 3 weeks. Toripalimab will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Also known as: JS001

Arm 1 (PD-1+NVB); Arm 2 (PD-1+NVB+Bev); Arm 3 (PD-1+NVB+DDP); Arm 4 (PD-1+VEX)

Bevacizumab 5 mg/kg BIOLOGICAL

Bevacizumab 5 mg/kg IV infusion every 3 weeks. Bevacizumab will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Arm 2 (PD-1+NVB+Bev)

Cyclophosphamide 50 mg DRUG

50 mg per day. Cyclophosphamide will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Arm 4 (PD-1+VEX)

Capecitabine 500Mg Oral Tablet DRUG

500mg three times a day. Capecitabine will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Arm 4 (PD-1+VEX)

Cisplatin DRUG

Cisplatin 50mg/m2 IV infusion every 3 weeks. Cisplatin will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Arm 3 (PD-1+NVB+DDP)

Eligibility Criteria

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

You may qualify if:

• Female patients with life expectancy ≥ 3 months, age ≥ 18 years at the time
• informed consent is signed.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 as assessed within 21 days prior to first dosage.
• Subjects with HER2 negative metastasis breast cancer, source documented, defined as per American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines.
• Subjects previously treated with no more than one prior line of standard chemotherapy
• Subjects with measurable metastatic disease defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines.
• Subjects may previously exposed to anthracyclines (e.g. doxorubicin, epirubicin) and/or taxanes (e.g., paclitaxel, docetaxel) including:
• has been pretreated in the adjuvant or neoadjuvant setting with anthracyclines and/or taxanes before breast cancer relapsing;
• has experienced treatment failure while receiving or after completing anthracycline- and/or taxane- based chemotherapy;
• not suitable for the choice of anthracycline- and/or taxane- based chemotherapy as first-line treatment in the judgment of investigator.
• Prior radiotherapy must have completed before randomization, with full recovery from acute radiation side effects. An interval of less than 4 weeks after radiotherapy was not allowed.Concurrent limited field radiation therapy (RT) is allowed. At least one measurable lesion must be completely outside the radiation portal in accordance with RECIST 1.1 guidelines;
• At least 30 days from major surgery before randomization, with full recovery;
• Adequate bone marrow function as evidenced by the following:
• Absolute Neutrophil Count (ANC) ≥ 1500/mm2;
• Platelets ≥ 100,000/mm2;

You may not qualify if:

• History of, or current active cancer other than breast cancer, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years.
• Patients with medical conditions that the only manifestation is hydrothorax, ascites, bone lesions or other un-measurable diseases.
• Subjects with visceral crisis in the judgment of investigator. Visceral crisis is defined as severe organ dysfunction as assessed by signs and symptoms, laboratory studies, and rapid progression of disease. Visceral crisis is not the mere presence of disease of visceral metastases, but implies important visceral compromise leading to a clinical indication for a more rapidly efficacious therapy, particularly since chemotherapy option at progression will probably not be possible.
• Malabsorption syndrome or disease significantly affecting gastro-intestinal function or major resection of the stomach or proximal small bowel that could affect absorption of Oral NVB.
• Subjects with dysphagia, or inability to swallow the tablets.
• Subjects with symptoms suggesting central nervous system (CNS) involvement or leptomeningeal metastases, any suspicious sins or symptoms of CNS involvement or leptomeningeal metastases should be excluded by CT or MRI scans.
• Other serious illness or medical conditions by the investigator during screening:
• Clinically significant cardiac disease;
• Unstable diabetes;
• Uncontrolled hypercalcemia;
• Clinically significant active infections (current or in the last two weeks).
• Previous organ allograft.
• Current peripheral neuropathy ≥grade 2 according to NCI version 4.0 criteria.
• Concomitant hormonal therapy for MBC.
• Ongoing anti-coagulation therapy.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead
• Beijing Huanxing Cancer Hospital: collaborator

Study Sites (2)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Huanxing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Related Publications (1)

• Mo H, Yu Y, Sun X, Ge H, Yu L, Guan X, Zhai J, Zhu A, Wei Y, Wang J, Yan X, Qian H, Xu B, Ma F. Metronomic chemotherapy plus anti-PD-1 in metastatic breast cancer: a Bayesian adaptive randomized phase 2 trial. Nat Med. 2024 Sep;30(9):2528-2539. doi: 10.1038/s41591-024-03088-2. Epub 2024 Jul 5.

  PMID: 38969879 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine; toripalimab; Bevacizumab; Cyclophosphamide; Capecitabine; Tablets; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dosage Forms; Pharmaceutical Preparations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Fei Ma

CONTACT

86-10-87788060; drmafei@126.com

Hongnan Mo

CONTACT

86-10-87788120

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 15, 2020
• Study Start: April 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: February 25, 2022

Record last verified: 2022-02

Locations

CN (2)