Phase II Study of PD-1 Antibody Combined With Radiotherapy in Recurrent or Metastatic Adrenal Cortical Carcinoma

NCT06587802 | Recruiting Phase 2

• 1 other identifier: SL-B2024-545-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adrenocortical Carcinoma

Keywords

Adrenocortical Carcinoma; radiotherapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From study enrollment to the time of tumor progression, at least 3 year follow-up

Secondary Outcomes (4)

• Overall survival time

  From study enrollment to the end of treatment or death up to 4 years follow-up

• Duration of remission

  From complete or partial response of tumor to the end of tumor progression or death, at least 3 year follow-up

• Objective response rate

  From study enrollment to the end of complete response or partial response of tumor, at least 3 year follow-up

• Duration of remission

  From partial response or completed response of tumor to the end of tumor progression or death, at least 3 years follow-up

Study Arms (1)

Experimental group

EXPERIMENTAL

SBRT radiotherapy (radiotherapy dose: 40Gy, 5 times, 8Gy each time, number of metastatic radiotherapy: ≤5).At the end of radiotherapy, 240mg of triplizumab was administered intravenously every cycle (21 days)

Drug: Triprolizumab; Device: rodiotherapy

Interventions

Triprolizumab DRUG

At the end of radiotherapy, 240mg of triplizumab was administered intravenously every cycle (21 days)

Experimental group

rodiotherapy DEVICE

SBRT radiotherapy (radiotherapy dose: 40Gy, 5 times, 8Gy each time, number of metastatic radiotherapy: ≤5)

Experimental group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Adrenocortical Carcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Central Study Contacts

Shengjie Guo, doctor

CONTACT

+86 13416140919; guoshj@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of urology, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: September 19, 2024
• Study Start: March 14, 2025
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): March 14, 2027
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (1)