Trial Title:
Exploratory Study on the Safety and Efficacy of Disitamab Vedotin in Combination with Anlotinib Hydrochloride for the Treatment of HER-2-expressing Recurrent Platinum-resistant Ovarian Cancer.
NCT ID:
NCT06660511
Condition:
Ovarian Cancer Recurrent
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Recurrence
Disitamab vedotin
Conditions: Keywords:
Ovarian Cancer Recurrent
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin in Combination With Anlotinib Hydrochloride
Description:
The dose of Disitamab Vedotin(RC48) is 2.0 mg/kg iv q2w d1; The dose of Anlotinib
Hydrochloride Capsules is 10mg po qd (recommended to be taken before meals and at the
same time every day), taken orally continuously for 2 weeks and stopped for 1 week, with
a treatment cycle of 21 days.
Main research endpoint: Objective response rate (ORR)
Secondary study endpoint:
1. Progression free survival (PFS)
2. Overall survival (OS)
3. Disease Control Rate (DCR)
4. Objective Duration of Response (DoR)
Arm group label:
Experimental
Other name:
RC48 combined with Anlotinib Hydrochloride
Other name:
RC48 combined with AL3818
Other name:
RC48 combined with Anlotinib
Summary:
Ovarian cancer is one of the three major malignant tumors of the female reproductive
system. Even if newly diagnosed ovarian cancer patients undergo ideal tumor cell
reduction surgery and postoperative chemotherapy, 70% to 80% of ovarian cancer patients
still experience recurrence. According to the length of PFI (platinum free interval),
recurrent ovarian cancer (ROC) can be classified into platinum resistant ROC (<6 months)
and platinum sensitive ROC (>6 months). There is currently no optimal treatment plan for
platinum resistant ovarian cancer (PROC), and the prognosis for patients is poor. The
guidelines recommend non platinum monotherapy chemotherapy for patients with PROC, but
non platinum monotherapy has a low objective response rate (ORR) (<20%), progression free
survival (PFS) (<4 months), and overall survival (OS,<12 months), with significant
adverse reactions and affecting quality of life. Therefore, PROC patients urgently need
new and better treatment options.
Antibody conjugated drugs (ADCs) have made breakthrough therapeutic progress in multiple
tumor types, and currently ADCs have been approved by the FDA for the treatment of
cervical cancer and ovarian cancer. HER2 (Human Epidermal Growth Factor Receptor 2) is a
member of the epidermal growth factor receptor (EGFR) family, also known as the tyrosine
protein kinase receptor. Research has shown that HER2 expression is associated with poor
prognosis in ovarian cancer, and patients with HER2 positive expression have a worse
prognosis. Vidiximab (RC48) is a novel HER2 antibody conjugate drug that received
Breakthrough Therapy Design from the US Food and Drug Administration (FDA) in April 2020.
Preclinical studies of ovarian cancer have shown that vediximab exhibits effective
cytotoxicity against HER2 expressing ovarian tumor cell lines. Meanwhile, the
registration study of RC48 for gynecological tumors is underway, and its latest data was
reported at the 2024 European Congress of Gynecological Oncology (ESGO), which showed
that in patients with recurrent or metastatic cervical cancer, the ORR of RC48
monotherapy was 36.4%, the median PFS was 4.37 months, and the 1-year OS was 66%.
Compared to other chemotherapy drugs, it also has significant advantages in terms of
toxic side effects, with severity mostly ranging from grade 1-2. Symptomatic treatment
can achieve complete recovery or relief.
Anti angiogenic drugs, including anti vascular endothelial growth factor (VEGF)
antibodies and multi-target tyrosine kinase inhibitors (TKIs), are considered potential
targets for treating platinum resistant/refractory ovarian diseases . Anlotinib is a
novel oral multi-target tyrosine kinase inhibitor (TKIs) . Monotherapy for PROC has
achieved initial efficacy, with an ORR of 31.2%, a median PFS of 5.3 months, and a
12-month OS rate of 90.9%. In terms of safety, most of the toxic side effects are grade
1-2.
Good progress has been made in preclinical and clinical trials of ADC in combination with
other anti-cancer drugs, including chemotherapy, molecular targeted drugs, anti
angiogenic drugs, and immunotherapy. Among them, anti angiogenic drugs may promote the
penetration and exposure of ADC to tumor cells, playing a mutually reinforcing role.
Research on the combination of RC48 and anlotinib is also actively underway in other
tumor types.
In summary, this study creatively conducted exploratory research in clinical PROC
patients based on the different expression levels of the molecular target HER2, and
adopted targeted medication according to the molecular target. At the same time, in terms
of combination therapy, low toxicity and high efficiency, different toxic side reaction
spectra, different mechanisms of action, and synergistic effects of dual anti-tumor drugs
were selected for combination therapy. Based on the above evidence, an exploratory study
was conducted on the safety and efficacy of vediximab combined with anlotinib in the
treatment of HER-2 expressing recurrent platinum resistant ovarian cancer, aiming to
explore the efficacy of vediximab combined with anlotinib in PROC patients, in order to
further improve the remission rate and quality of life of patients while prolonging their
survival.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The subjects voluntarily joined this study, signed an informed consent form, and
showed good compliance;
2. Age ≥ 18 years old when signing the informed consent form;
3. Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
diagnosed by organizational or cellular pathology;
4. The subjects can provide tumor primary or metastatic site specimens for HER2
detection (paraffin blocks, paraffin embedded sections, or fresh tissue sections are
all acceptable), and the immunohistochemical (IHC) test results show HER2
expression: IHC 1+, 2+, or 3+; 4) ECOG PS: 0-1 point;
5. Expected survival period>12 weeks;
6. Adequate heart, bone marrow, liver, and kidney function (based on normal values at
the research center);
7. At least one measurable lesion defined in RECIST version 1.1;
8. Women of childbearing age must meet one of the following conditions:
- Surgical sterilization has been performed; ② Menopausal individuals who have
stopped menstruating for at least one year; ③ Having the ability to conceive
requires meeting the following conditions:; The serum pregnancy test result
before the first medication is negative and must be a non lactating subject;
During the entire study period, it was agreed to use a recognized method of
contraception (such as oral contraception, injection contraception, or
implanted barrier contraception, spermicides and condoms, or intrauterine
devices), and the contraceptive method remained unchanged throughout the study
period.
Exclusion criteria：
1. Previously received ADC drugs for HER2 treatment or similar TKI small molecule anti
angiogenic drugs such as anlotinib hydrochloride;
2. Subjects with primary platinum refractory diseases;
3. Patients with untreated central nervous system metastases (including new and
progressive brain metastases), a history of leptomeningeal metastases or malignant
meningitis;
4. Individuals with symptoms and signs of intestinal obstruction and requiring
parenteral nutrition and fluid replacement;
5. Patients with any signs of bleeding or history of bleeding, regardless of the
severity: patients who have experienced any bleeding or bleeding events ≥ CTCAE
grade 3 within the 4 weeks prior to the first dose; Or there may be unhealed wounds,
fractures, active ulcers in the stomach and duodenum, ulcerative colitis and other
digestive diseases.
6. Within 6 months, there have been incidents of arterial/venous thrombosis, such as
cerebrovascular accidents (including temporary ischemic attacks, cerebral
hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
(Individuals with a tendency towards thrombosis or undergoing anticoagulant therapy
are allowed to use prophylactic anticoagulant therapy)
7. Serious cardiovascular and cerebrovascular diseases or discomfort, including but not
limited to the following diseases:
- Diagnosed history of heart failure or systolic dysfunction (LVEF<50%)
- High risk uncontrolled arrhythmia
- Angina pectoris, acute myocardial infarction
- Clinically significant heart valve disease
- Poor control of hypertension (systolic blood pressure>180 mmHg and/or diastolic
blood pressure>100 mmHg)
8. The toxicity caused by previous anti-tumor treatments has not yet recovered to CTCAE
(version 5.0) grade 0-1 (excluding 2nd degree hair loss);
9. Individuals who have undergone major surgery within 4 weeks prior to their first
medication and have not fully recovered, or are expected to undergo surgical
treatment;
10. Patients with other malignant tumors within 3 years prior to the first use of
medication, excluding papillary thyroid carcinoma, basal cell or squamous cell
carcinoma that have been adequately treated and have no evidence of disease
recurrence, as well as other in situ cancers that have been adequately treated and
have no evidence of disease recurrence (including but not limited to cervical
primary cancer, ductal carcinoma in situ of the breast, etc.);
11. Imaging (CT or MRI) shows that the tumor has invaded important blood vessels or is
highly likely to invade important blood vessels and cause fatal massive bleeding
during subsequent studies, as determined by the researcher;
12. Patients with clinical symptoms of pleural effusion, pericardial effusion, or
ascites who require repeated puncture and drainage, or those who have received
treatment within the previous month for the purpose of drainage;
13. Individuals with a known history of allergies to the components of this medication
regimen;
14. Pregnant and lactating female patients;
15. Suffering from serious accompanying diseases or other comorbidities that may
interfere with planned treatment, or any other circumstances that the researcher
deems unsuitable for the patient to participate in this study
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Xiangya Second Hospital of Central South University
Address:
City:
Changsha
Country:
China
Status:
Recruiting
Start date:
October 15, 2024
Completion date:
October 15, 2025
Lead sponsor:
Agency:
Second Xiangya Hospital of Central South University
Agency class:
Other
Source:
Second Xiangya Hospital of Central South University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06660511
