Trial Title:
Phase II Study of PD-1 Antibody Combined with Radiotherapy in Recurrent or Metastatic Adrenal Cortical Carcinoma
NCT ID:
NCT06587802
Condition:
Adrenocortical Carcinoma
Conditions: Official terms:
Carcinoma
Adrenocortical Carcinoma
Conditions: Keywords:
Adrenocortical Carcinoma
radiotherapy
immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Triprolizumab
Description:
At the end of radiotherapy, 240mg of triplizumab was administered intravenously every
cycle (21 days)
Arm group label:
Experimental group
Intervention type:
Device
Intervention name:
rodiotherapy
Description:
SBRT radiotherapy (radiotherapy dose: 40Gy, 5 times, 8Gy each time, number of metastatic
radiotherapy: ≤5)
Arm group label:
Experimental group
Summary:
Adrenal cortical cancer is an extremely rare and highly aggressive malignancy with an
incidence of 0.7-2 per million people · year and a 5-year overall survival rate of
15-44%, among which the 5-year survival rate of stage IV cortical cancer is only 13% and
the prognosis is poor. Complete surgical resection is one of the most important ways to
cure cortical cancer, but the surgical trauma is large, the complications are high, the
postoperative recovery of patients is slow, and the tumor is difficult to achieve
complete resection, and the postoperative recurrence and metastasis rate of patients is
high, even for localized cortical cancer (stage I-III), the recurrence and metastasis
rate is still close to 60%.
Recurrent or metastatic cortical cancer is mainly treated with drugs. However, the
current first-line drug therapy is only 22.3% effective, the tumor progression-free time
is 5.6 months, and the serious adverse reaction rate is as high as 58.1%.
The effective rate of second-line treatment with chemotherapy and targeted drugs was less
than 10%, and the tumor progression-free time was only 2.8 months.
The Phase II study of PD-1 monoclonal antibody in the treatment of cortical cancer showed
that the treatment effective rate was 23%, and the tumor progression-free survival time
was 2.1 months, which was comparable to the first-line regimen, and has been approved by
the guidelines for advanced cortical cancer.
Radiation therapy has high efficiency and local control rate, small side effects, and can
inhibit tumor growth, relieve local pressure and pain. However, it only has a good effect
on the irradiated site, and it is difficult to inhibit the progression of
non-radiotherapy lesions and the generation of other new lesions.
The synergistic effect of immunotherapy combined with radiation therapy for metastatic
stoves has been confirmed in many solid tumors such as kidney cancer, which can improve
the local control rate of solid tumors and prolong the time of tumor progressive-free.
In the early stage, this research team applied PD-1 monoclonal antibody combined with
radiotherapy to treat recurrent or metastatic adrenal cortical cancer in many cases after
receiving first-line drug therapy regimen, which not only achieved local control of the
radiotherapy focus, but also inhibited the progression of other metastases, and achieved
longer disease control effect.
Detailed description:
Adrenocortical Carcinoma (ACC) is an extremely rare and highly aggressive malignant tumor
with an incidence of 0.7-2 per million people and poor prognosis. The 5-year overall
survival rate is 15-44%, and the 5-year survival rate of stage IV ACC is only 13%.
Surgical complete resection (R0) is one of the most important ways to cure ACC. However,
even for localized ACC (stage I-III), there is still a recurrence and metastasis rate of
nearly 60%, due to reasons including surgical failure to achieve R0 resection, tumor
rupture, and postoperative hematologic and lymphatic metastasis. Recurrent or metastatic
ACC is mainly treated with systemic drugs, mitotan monotherapy or mitotan combined with
cisplatin based chemotherapy (mitotan ± etoposide, adriamycin and cisplatin: EDP-M
protocol is currently the first-line protocol for advanced ACC, but the objective
response rate (ORR) of EDP-M is only 22.3%, the progression-free survival (PFS) is 5.6
months, and the grade 3-4 adverse reactions are as high as 58.1%. Treatment options for
patients with recurrent or metastatic ACC after first-line treatment progress are more
limited and less effective. The ORR of second-line chemotherapy for advanced ACC was less
than 10%. Targeted drugs such as Sunitinib for second-line treatment of advanced ACC had
an ORR of 0, and PFS was only 2.8 months. Five clinical studies have been conducted to
investigate the efficacy of immunotherapy for adrenal cortical cancer. The results of a
phase II study on the treatment of ACC with PD-1 monoclonal antibody showed that ORR
could reach 23%, which is the regimen with the highest objective response rate at
present. Therefore, the guidelines recommend PD-1 monoclonal antibody for advanced ACC,
but the PFS of PD-1 monoclonal antibody is only 2.1 months. Therefore, how to prolong PFS
with high ORR is a difficult problem in the treatment of advanced ACC.
For recurrent or metastatic ACC, surgical palliative resection of metastasis can reduce
tumor or alleviate symptoms. However, due to large surgical trauma, high complications,
slow postoperative recovery of patients, difficult R0 resection of tumors, and high
postoperative recurrence and metastasis rate of patients, it is still controversial
whether palliative surgery for advanced ACC can bring survival benefits to patients. The
guidelines also recommend that radiotherapy can be used for advanced ACC, with high ORR
and local control rate, small side effects, inhibiting tumor growth, relieving local
pressure and pain. However, radiotherapy is a local treatment that only has a good effect
on the irradiated site, and it is difficult to inhibit the progression of
non-radiotherapy lesions and the emergence of other new lesions. Therefore, the effect of
radiotherapy alone on the overall disease control of patients with advanced ACC
recurrence or metastasis is still unsatisfactory.
The synergistic effect of immunotherapy combined with radiotherapy for metastatic stoves
has been demonstrated in many solid tumors such as kidney cancer. The ORR of advanced
renal clear cell carcinoma treated with PD-1 monoclonal antibody alone was only 36.5%,
the median PFS time was 7.1 months, and the 2-year PFS rate was 22.3%, while the ORR of
advanced renal clear cell carcinoma treated with PD-1 monoclonal antibody combined with
radiotherapy was 63%, PFS was 15.6 months, and the 2-year PFS rate was 45%. Therefore,
immunotherapy combined with radiotherapy can improve the local control rate and prolong
the PFS time of metastatic renal carcinoma. The ORR of PD-1 monoclonal antibody
monotherapy for advanced ACC was 23% and PFS was 2.1 months. Although the ORR was similar
to that of EDP-M first-line regimen, the PFS was shorter. Therefore, it is of great
clinical significance to explore whether PD-1 monoclonal antibody combined with
radiotherapy for advanced ACC can obtain higher ORR and longer PFS.
In the early stage, this research team applied PD-1 monoclonal antibody combined with
SBRT to treat recurrent or metastatic adrenal cortical cancer in multiple cases of
recurrent or metastatic ACC after treatment with first-line EDP-M protocol, which not
only achieved local control of radiotherapy lesions, but also inhibited the progression
of other metastasies, and achieved longer disease control effect (ORR: 4/7, PFS: July).
On the basis of previous practice, our team plans to further conduct prospective
exploratory clinical research on the efficacy and safety of PD-1 monoclonal antibody
combined with radiotherapy in the treatment of recurrent or metastatic adrenal cortical
carcinoma, so as to provide more safe and effective treatment options for this rare
tumor.
Main purpose:
To observe and evaluate the progression-free survival time of PD-1 monoclonal antibody
combined with radiotherapy in the treatment of recurrent or metastatic adrenal cortical
carcinoma
Secondary purpose:
To observe and evaluate the secondary efficacy indexes and safety of PD-1 monoclonal
antibody combined with radiotherapy in the treatment of recurrent or metastatic adrenal
cortical carcinoma
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients voluntarily participated in this study and signed informed consent;
- Patients ≥18 years old;
- ECOG score ≤2 points; Expected survival ≥6 months;
- Pathological diagnosis of adrenal cortical carcinoma;
- Inability or unwillingness to surgically resect recurrent or metastatic adrenal
cortical cancer;
- Adrenal cortical cancer has recurred or metastasized after receiving mitotan
monotherapy, chemotherapy, or first-line regimens based on mitotan combined with
cisplatin chemotherapy and has progressed, unable to tolerate or unwilling to accept
the regimens;
- Have at least one measurable lesion (RECIST1.1);
- The main organs function well, and the laboratory examination indicators meet:
- (1) Blood routine examination: Hemoglobin (HB) ≥90g/L(5.6mmol/L); Absolute
neutrophil count (ANC) ≥1.5×109/L; Total white blood cells ≥3.5×109/L;
- Platelet (PLT) ≥80×109/L; (2) Blood biochemical examination:
① Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN
(liver metastasis/bone metastasis ≤5× ULN; Tumor bone metastasis ≤5ULN);
② Serum total bilirubin (TBIL) ≤1.5×ULN;
- Serum creatinine Cr≤1.5×ULN or creatinine clearance ≥60ml/min; Blood urea
nitrogen (BUN)≤2.5× upper limit of normal value (ULN); ④ Albumin (ALB)≥30g/L;
(3) Blood coagulation test: Activated partial thromboplastin time (APTT),
International Normalized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
- Women of childbearing age must confirm their non-pregnant status before enrollment,
and all enrolled subjects (whether male or female) should take adequate
contraceptive measures during the whole treatment period and 4 weeks after the end
of treatment;
- The subjects were willing to return to the hospital for follow-up and had good
compliance.
Exclusion Criteria:
- Receiving anti-tumor monoclonal antibodies or other investigational drugs before
enrollment
- Previously received other anti-PD-1 monoclonal antibody therapy or other drug
therapy for PD-1 / PD-L1
- Radiotherapy has been used in the lesion area in the past
- The lesion invades the intestinal duct, and there are contraindications to
radiotherapy such as the risk of intestinal fistula caused by radiotherapy
- Known allergic reaction to the active ingredient of PD-1 monoclonal antibody or any
excipients
- Have a medical condition that interferes with oral medication, including but not
limited to difficulty swallowing, chronic diarrhea, or intestinal obstruction
- Uncontrolled heart disease, such as heart failure with NYHA rating ≥2, unstable
angina pectoris, history of myocardial infarction in the past year, and ventricular
or supraventricular arrhythmias requiring treatment
- Central nervous system metastasis with clinical symptoms, such as brain edema,
requiring hormonal intervention, or brain metastasis progression;
- Serious infections (CTCAE > Grade 2) occurred within 4 weeks prior to the first
use of the study drug, such as severe pneumonia, bacteremia, and infection
complications requiring hospitalization; Baseline chest imaging examination
indicating active lung inflammation, signs and symptoms of infection within 2 weeks
prior to first use of the study drug, or the need for oral or intravenous antibiotic
treatment (excluding prophylactic antibiotic use)
- Receive systemic sex hormone or other immunosuppressive therapy with an equivalent
dose greater than 10mg prednisone/day within 4 weeks of signing the informed
consent. Participants with a systemic sex hormone dose ≤10mg prednisone/day or
inhaled/topical corticosteroids could be enrolled
- chronic hepatitis B active stage or active hepatitis C patients. Screening period
hepatitis B surface antigen (HepatitsBSurfaceAntigen, HBsAg) or hepatitis b core
antibody (HBcAb HepatitsBcoreAntibody,) or hepatitis c virus (HepatitisCVirus, HCV)
antibody positive patients, Only through HepatitisBVirus (HBV) DNA detection (no
more than 104 copies /mL or 2000IU/mL) and HCVRNA detection (no more than the lower
limit of the assay) will he be included in the group test after the disease has been
controlled. Hepatitis B virus carriers, hepatitis B whose disease has been
controlled after drug treatment (no more than 104 copies /mL of DNA or 2000IU/mL),
and cured hepatitis C patients can be enrolled
- Significant vital organ dysfunction or uncontrollable comorbiditions, including but
not limited to uncontrolled hypertension, decompensated cirrhosis, active peptic
ulcer or bleeding disease
- History of interstitial lung disease or non-infectious pneumonia; Participants with
a history of drug-induced or radiation-induced non-infectious pneumonia without
symptoms were admitted
- Pregnant and lactating women and subjects of childbearing age who do not want to
take contraceptive measures
- Persons with mental illness, a history of alcohol or drug abuse, or inability to
obtain informed consent
- Other researchers have determined that participants are not suitable for this study,
such as serious diseases, including mental illness, serious abnormal test results,
and other social or family high-risk risk factors that require timely intervention
- refuse or can not sign the informed consent.
- Patients suspected of having other primary cancers; Patients with other primary
malignancies within the 5 years prior to the study period (other than adequately
treated cervical or skin cancer in situ, such as basal cell carcinoma, squamous cell
carcinoma, or non-melanoma skin cancer)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Country:
China
Contact:
Last name:
Shengjie Guo
Phone:
86+ 13416140919
Email:
guoshj@sysucc.org.cn
Start date:
September 30, 2024
Completion date:
September 30, 2028
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06587802
