Trial Title:
Camrelizumab Plus Fluzoparib for TP-53 Mutated Endometrial Cancer
NCT ID:
NCT06413992
Condition:
Endometrial Carcinoma
TP53 Mutation
Recurrent or Metastatic
Conditions: Official terms:
Endometrial Neoplasms
Paclitaxel
Carboplatin
Fluzoparib
Conditions: Keywords:
TP53-mutated, Endometrial Carcinoma,Camrelizumab, Fluzoparib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fluzoparib
Description:
During the maintenance phase of treatment. Oral administration of Fluzoparib capsules at
a dose of 150mg（N=78 participants）, once in the morning and once in the evening until
disease progression, intolerable toxicity, death, or up to a maximum of 2 years.
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Intervention type:
Drug
Intervention name:
Camrelizumab
Description:
During the maintenance phase of treatment. Camrelizumab, 200 mg administered
intravenously every 3 weeks until disease progression, intolerable toxicity, death, or up
to 2 years.
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Arm group label:
Camrelizumab without Fluzoparib as maintainance therapy
Intervention type:
Drug
Intervention name:
paclitaxel (albumin bound)
Description:
Paclitaxel (albumin-bound) for injection, 260 mg/m^2 administered intravenously in 3-week
cycles for 6 cycles.
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Arm group label:
Camrelizumab without Fluzoparib as maintainance therapy
Intervention type:
Drug
Intervention name:
Carboplatin injection
Description:
AUC=5 Intravenous dosing is administered every 3 weeks for a total of 6 treatment cycles.
Specific dosing cycles may be determined by the investigator
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Arm group label:
Camrelizumab without Fluzoparib as maintainance therapy
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
AUC=5 Intravenous dosing is administered every 3 weeks for a total of 6 treatment cycles.
Specific dosing cycles may be determined by the investigator
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Arm group label:
Camrelizumab without Fluzoparib as maintainance therapy
Intervention type:
Radiation
Intervention name:
External irradiation
Description:
Non-essential, decision to combine is made by the principal investigator based on the
patient's condition.
Arm group label:
Camrelizumab with Fluzoparib as maintainance therapy
Arm group label:
Camrelizumab without Fluzoparib as maintainance therapy
Summary:
This study is an open-label Phase II randomized controlled trial designed to evaluate the
safety and efficacy of camrelizumab plus fluzoparib maintenance therapy in patients with
recurrent or metastatic TP-53 mutated Endometrial Cancer. The study will also explore the
prevalence of homologous recombination reficiency in Chinese patients with TP-53 mutated
endometrial cancer and its therapeutic significance.
Detailed description:
The treatment of recurrent or metastatic endometrial carcinoma (R/M-EC) has entered the
era of molecular marker oriented precision therapy. Meanwhile, several large multicenter
Phase III RCT studies have been conducted, such as NRG-GY018, RUBY, DUO-E and AtTEnd, and
suggested that chemotherapy combined with immunotherapy could significantly improve the
prognosis of R/M-EC. Unfortunately, the efficacy of ICBs in Asian R/M-EC population is
not obvious, with small size.
On the other hand, up to 63% of patients with R/M-EC have TP-53 gene mutations (TP53mut).
And the efficacy of chemotherapy combined with immunotherapy in thse patients is
controversial. In the RUBY study, TC combined with Dostarlimab reduced the risk of death
in patients with TP53mut-R/M-EC by 59 percent. However, in the DUO-E study, chemotherapy
combined with Durvalumab failed to improve serous -EC in 154 patients (approximately 92%
TP53mut). Therefore, how to optimize the strategy of chemotherapy combined with
immunotherapy in TP53mut-R/M-EC is urgently needed.
Considering TP53mut-EC patients with tumor local T-lymph Cell infiltration and PD-L1
expression were significantly higher than those of TP-53 gene wild type (TP53wt)
patients. It was also suggested that ICB and PARPi had a good synergistic effect. The
DUO-E study revealed the combination of Durvalumab and Olaparib maintenance therapy
significantly improves the prognosis of serous EC.
Therefore, as an investigator-initiated open-label Phase II randomized controlled study,
the study will include 117 patients with TP53mut-R/M-EC, and randomly divided 2:1 into
experimental group and control group to evaluate the safety and efficacy of camrelizumab
plus fluzoparib maintenance therapy in patients with recurrent or metastatic TP-53
mutated Endometrial Cancer. The study will also explore the prevalence of homologous
recombination reficiency in Chinese patients with TP-53 mutated endometrial cancer and
its therapeutic significance.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥18
- Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG): 0-2. Expected
survival ≥ 6 months.
- Patients with newly diagnosed International Federation of Gynecology and Obstetrics
(FIGO) 2009 stage III-IV endometrial cancer or recurrent endometrial cancer after ≤
1 line of platinum-based chemotherapy (including neoadjuvant, adjuvant, and
concurrent chemotherapy). For patients who have failed platinum-based chemotherapy,
a platinum-free interval of ≥ 12 months is required.
- No restriction on pathological type, abnormal p53 expression indicated by
immunohistochemistry, and confirmation of TP53 gene mutation by Sanger sequencing or
next-generation sequencing (NGS).
- No prior treatment with immune checkpoint blockade (ICB) or poly (ADP-ribose)
polymerase inhibitor (PARPi).
- Discontinuation of previous radiation therapy, chemotherapy, or hormone therapy for
at least 4 weeks.
- Adequate organ function as follows (no use of drugs containing blood components or
corrective treatment with hematopoietic growth factors in the 7 days prior to
randomization): Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤
2.5 times the upper limit of normal (≤ 5 times for patients with liver metastasis)
and total bilirubin ≤ 1.5 times the upper limit of normal; serum creatinine ≤ 1.5
times the upper limit of normal; platelets ≥ 90,000 cells/mm3, hemoglobin ≥ 90 g/L,
and neutrophils ≥ 1,500/mm3.
- Thyroid function prior to randomization: Thyroid-stimulating hormone (TSH) level ≤ 1
times the upper limit of normal, or if TSH is not within the normal range, free T4 ≤
1 times the upper limit of normal.
- Peripheral neuropathy grade < 2 (Common Terminology Criteria for Adverse Events,
CTCAE 5.0) before treatment.
- Signed informed consent and ability to provide tumor tissue samples from initial
diagnosis/recurrence for homologous recombination deficiency (HRD) testing.
- Willingness to comply with clinic visits and follow-up.
Exclusion Criteria:
- Currently participating in another clinical trial or within 4 weeks since completing
another clinical trial.
- Known allergy to any components of the investigational drug.
- Previous treatment with immune checkpoint inhibitors, including but not limited to
other anti-PD-1 and anti-PD-L1 antibodies.
- Patients requiring the use of immunosuppressive medications.
- Previous treatment with poly (ADP-ribose) polymerase inhibitors (PARPi).
- Patients requiring systemic or absorbable topical corticosteroids at an
immunosuppressive dose, or patients who have used prednisone or equivalent drugs at
a dose >10 mg/day in the two weeks prior to taking the study drug.
- Patients with any active autoimmune disease or a history of autoimmune diseases,
including but not limited to active hepatitis, pneumonia, uveitis, colitis
(inflammatory bowel disease), pituitary inflammation, vasculitis, nephritis,
hyperthyroidism, and hypothyroidism, excluding resolved childhood asthma/atopic
diseases and vitiligo. Patients with intermittent use of bronchodilators or other
medical interventions for asthma should also be excluded.
- Patients in the active infectious phase requiring antimicrobial treatment (e.g.,
antibiotics, antiviral drugs, antifungal drugs).
- History of immunodeficiency, including human immunodeficiency virus (HIV)
seropositivity or other acquired or congenital immunodeficiency diseases.
- Uncontrolled clinically significant cardiac symptoms or diseases within the past
year, including but not limited to New York Heart Association (NYHA) class II or
higher heart failure, unstable angina, myocardial infarction within the past year,
atrial fibrillation, clinically significant supraventricular or ventricular
arrhythmias requiring treatment or intervention, PR interval >250 ms, or QTc ≥470
ms.
- Arterial or venous thrombosis within the past 6 months.
- Poorly controlled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic
blood pressure ≥90 mmHg) despite antihypertensive medication, proteinuria ≥(++) and
24-hour total urinary protein >1.0 g.
- Coagulation abnormalities (international normalized ratio [INR] >2.0, prothrombin
time [PT] >16s), bleeding tendency, or receiving thrombolytic or anticoagulant
therapy.
- Patients with other malignant tumors within the past 5 years, excluding basal cell
carcinoma of the skin and squamous cell carcinoma of the skin.
- Vaccination with live vaccines within 4 weeks prior to the first administration of
the investigational drug. Note: Administration of inactivated seasonal influenza
vaccines is allowed.
- History of substance abuse with psychotropic drugs and unable to quit, or patients
with psychiatric disorders.
- The investigator believes that any other medical, psychiatric, or social factors may
affect the rights, safety, ability to sign informed consent, patient's completion of
the study, or interpretation of study results.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital, Chinese Academy of Medical Sciences
Address:
City:
Beijing
Zip:
100021
Country:
China
Status:
Recruiting
Contact:
Last name:
SHUANGZHENG JIA
Start date:
May 10, 2024
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06413992
