Clinical trial NCT06396637: PD-1 Antibody and Sapropterin Dihydrochloride in Patients With PDAC
Official title: The Efficacy and Safety of PD-1 Antibody Combined With Sapropterin Dihydrochloride in Patients With Advanced Pancreatic Cancer Who Failed to Standard Treatment.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma Metastatic
Keywords: Pancreatic adenocarcinoma
PD-1 inhibitor
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Innovent Biologics (Suzhou) Co. Ltd.
First posted: 2024-05-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: PD-1 Antibody combined with Sapropterin Dihydrochloride
Primary purpose: TREATMENT

Brief summary: The prognosis for pancreatic cancer remains dismal, with current guidelines favoring FOLFIRINOX or AG (consisting of Gemcitabine and Abraxane) as the primary chemotherapeutic option. However, research has indicated limited benefits for patients with pancreatic cancer undergoing immunotherapy using Anti-PD-1 antibodies. In this context, researchers aim to investigate the therapeutic potential of Sapropterin Dihydrochloride combined with PD-1 antibody in patients with metastatic pancreatic cancer who failed to standard treatment.

Detailed description: There is no standard treatment for patients with metastatic pancreatic cancer who failed to FOLFIRINOX or AG (consisting of Gemcitabine and Abraxane). Patients with metastatic pancreatic cancer who are unable to tolerate or have failed to respond to standard chemotherapy will be enrolled in this clinical trial. They will be administered a combination treatment of Sapropterin Dihydrochloride and PD-1 antibody. The primary endpoints of this study are objective response rate and safety. The secondary endpoints will encompass overall survival, progression-free survival, and quality of life. The study aims to enroll a total of 20 participants.

Eligibility criteria: Inclusion Criteria:

* Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).
* Recurrent disease or metastatic disease evaluated by abdominal contrast-enhanced CT, MRI, and chest CT. PET/CT or other imaging examinations would be used if necessary.
* Fail or could not tolerate standard chemotherapy.
* ECOG score 0 or 1.
* Have measurable target lesion.
* Serum total bilirubin level is less than 1.5 x ULN. ALT and AST are less than 2 x ULN. Hemoglobin≥9g/dL, platelet≥75×10\*9/L, white blood count ≥3.0×10\*9/L, neutrophil ≥1.5×10\*9/L. Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate \> 60 mL/min.
* Signed informed consent.

Exclusion Criteria:

* History of participation of other clinical trials within 4 weeks
* Known or suspected allergy to Sintilimab or tetrahydrobiopterin.
* Female patients during pregnancy or lactation.
* Patients who lack the ability to provide informed consent due to psychological, family, social, or other factors.
* Patients with a history of other malignant tumors besides pancreatic cancer before enrollment, except for non-melanoma skin cancer, carcinoma in situ of the cervix, or cured early-stage prostate cancer.
* Patients with severe cardiac, pulmonary, hepatic, or renal dysfunction, hematopoietic system diseases, cachexia, or other conditions that are intolerable to radiotherapy, chemotherapy, or surgery.
* Patients with autoimmune diseases, a history of autoimmune diseases (such as colitis, hepatitis, hyperthyroidism, including but not limited to these diseases or syndromes), as well as a history of immune deficiency, including HIV-positive test results, or other acquired or congenital immune deficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation.
* Patients who require systemic corticosteroid therapy (\> 10 mg/day prednisone equivalent dose) or other immunosuppressive drugs within 14 days before the first administration or during the study. However, the following situations are allowed for enrollment: In the absence of active autoimmune diseases, patients are allowed to use topical or inhaled steroids, or adrenal hormone replacement therapy at a dose ≤ 10 mg/day prednisone equivalent dose.
* Patients with a history of interstitial lung disease or non-infectious pneumonia.
* Patients with active pulmonary tuberculosis infection detected through medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment, or patients with a history of active pulmonary tuberculosis infection more than 1 year ago but without proper treatment.
* Subjects with active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10\*4 copies/mL), hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the lower limit of detection of the analytical method).

Primary outcomes:
measure: Objective response rate
timeFrame: Every 6 weeks (2 cycles) from first treatment to disease progression or totally 2 years Based on irRECIST
measure: Adverse events by NCI-CTCAE v5.0
timeFrame: Every 3 weeks from first treatment to disease progression or totally 2 years Based on irRECIST
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to approximately 2 year
measure: Progression-Free Survival (PFS)
timeFrame: up to approximately 1 year
measure: EORTC QLQ-C30 survey
timeFrame: up to approximately 2 year
measure: EORTC-QLQ-PAN26 survey
timeFrame: up to approximately 2 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer center of Sun Yat-sen University
state: Guangdong
Study officials:
References: