Trial Title:
Anlotinib Plus Benmelstobart and AG in First-line Treatment of Advanced Metastatic Pancreatic Cancer (ALTER-PA-001)
NCT ID:
NCT06621095
Condition:
Pancreatic Cancer
First-line
Metastatic Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
Conditions: Keywords:
Metastatic Pancreatic Cancer
First-line
Immunotherapy
Angiogenesis inhibitors
Anlotinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
anlotinib + benmelstobart + nab-paclitaxel + gemcitabine
Description:
1. Before 8 cycles, anlotinib 8mg, po.qd, d1-14; benmelstobart: 1200mg, I.V., D1, Q3W;
nab-paclitaxel: 125mg/m2, I.V., D1, D8, Q3W; gemcitabine: 1000/m2, ivgtt for more
than 30min, D1, D8, Q3W. The above schemes are repeated every three weeks.
2. After 8 cycles, the regimen is changed to anlotinib 8mg, po.qd, d1-14;
benmelstobart: 1200mg, I.V., D1, Q3W; gemcitabine: 1000/m2, ivgtt for more than
30min, D1, D8, Q3W. The regimen is repeated every 3 weeks until the disease
progresses or unacceptable toxicity.
Arm group label:
anlotinib + benmelstobart + nab-paclitaxel + gemcitabine
Intervention type:
Drug
Intervention name:
nab-paclitaxel + gemcitabine
Description:
1. Before 8 cycles, nab-paclitaxel: 125mg/m2, I.V., D1, D8, Q3W; gemcitabine: 1000/m2,
ivgtt for more than 30min, D1, D8, Q3W. The above schemes are repeated every three
weeks.
2. After 8 cycles, the regimen is changed to gemcitabine: 1000/m2, ivgtt for more than
30min, D1, D8, Q3W. The regimen is repeated every 3 weeks until the disease
progresses or unacceptable toxicity.
Arm group label:
nab-paclitaxel + gemcitabine
Summary:
This study is designed to explore the efficacy and safety of anlotinib combined with
benmelstobart and AG (nab-paclitaxel and gemcitabine) as first-line treatment compared
with AG (nab-paclitaxel and gemcitabine) in metastatic pancreatic cancer.
Detailed description:
This is an open-label, multicenter, randomized controlled clinical trial. We plan to
recruit 104 subjects and randomly assign them in a 2:1 ratio to either the experimental
group receiving Anlotinib plus Benmelstobart plus Gemcitabine and Nab-Paclitaxel, or the
control group receiving Gemcitabine and Nab-Paclitaxel as initial treatment. Each cycle
of the aforementioned drugs will last three weeks, with tumor efficacy assessments
conducted at the end of cycles 2, 4, 6, and 8. After 8 cycles of treatment, patients in
the experimental group who achieve complete response (CR), partial response (PR), or
stable disease (SD) will continue with maintenance therapy using Anlotinib plus
Benmelstobart plus Gemcitabine. Similarly, after 8 cycles of treatment, patients in the
control group who achieve CR, PR, or SD will continue with maintenance therapy using
Gemcitabine monotherapy. Efficacy will be evaluated every 3 cycles (9 weeks) during the
maintenance phase until disease progression or intolerability. This study aims to
evaluate the efficacy and safety of the combination of Anlotinib and Benmelstobart with
Gemcitabine and Nab-Paclitaxel in treating metastatic pancreatic cancer, providing a new
treatment option for first-line therapy in patients with advanced metastatic pancreatic
cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 18-75 years old (including 18 and 75 years old);
- Histologically or cytologically confirmed diagnosis of metastatic pancreatic cancer;
- No prior systemic therapy for metastatic pancreatic cancer (allowable circumstances
for inclusion include recurrence more than 6 months after neoadjuvant
(chemo)radiotherapy plus radical surgery, or recurrence more than 6 months after the
completion of adjuvant (chemo)radiotherapy or radical concurrent chemoradiotherapy);
- At least one measurable lesion according to RECIST v1.1 criteria (any previous
radiotherapy-treated lesion that has not progressed cannot be selected as the target
lesion);
- Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
- Life expectancy ≥ 3 months;
- Adequate organ and bone marrow function, meeting the following criteria (within 7
days before enrollment):
1. Hematology:
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L Platelet count (PLT) ≥ 90 x
10^9/L Hemoglobin (HB) ≥ 90 g/L
2. Biochemistry:
Without liver metastasis: Serum total bilirubin (TBIL) ≤ 1.5x the upper limit
of normal (ULN); with liver metastasis: TBIL ≤ 2.5 x ULN.
Without liver metastasis: Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤ 3 x ULN; with liver metastasis: ALT and AST ≤ 5 x ULN.
Serum creatinine ≤ 1.5 x ULN and creatinine clearance rate ≥ 60 mL/min
(calculated by the Cockcroft-Gault formula).
3. Adequate coagulation function, defined as an international normalized ratio
(INR) or a partial thromboplastin time (APTT) ≤ 1.5 x ULN.
- Women of childbearing age need to take effective contraceptive measures.
Exclusion Criteria:
- Previously received treatment with vascular endothelial growth factor receptor
(VEGFR) inhibitors or immune checkpoint inhibitors;
- Received other systemic antitumor treatments within 4 weeks prior to enrollment,
including chemotherapy, signal transduction inhibitors, hormone therapy, biological
immunotherapy, targeted therapy, photodynamic therapy, and traditional Chinese
medicine with clear antitumor indications;
- Have other untreated or concurrent malignancies (excluding cervical carcinoma in
situ, well-controlled basal cell or squamous cell carcinoma of the skin, or
malignancy that has been treated and has shown no signs or evidence of recurrence
for more than 3 years, and patients who do not require systemic therapy at the time
of signing informed consent);
- Presence of central nervous system (CNS) metastases or brain metastases before
enrollment;
- Underwent any surgery (excluding biopsy), invasive treatment or operation without
complete healing of surgical incisions within 4 weeks before enrollment (excluding
venous catheter placement and puncture drainage);
- Received radiotherapy within 4 weeks before enrollment (allowable if at least 2
weeks have passed since palliative radiotherapy for bone lesions was completed
before starting study medication);
- Previously received any organ transplantation;
- Clinically symptomatic ascites, pleural effusion, or pericardial effusion requiring
puncture or drainage, or received drainage of effusions within 14 days before the
first dose;
- International normalized ratio (INR) > 1.5 or partial thromboplastin time (APTT) >
1.5 x ULN;
- Clinically significant electrolyte abnormalities as determined by the investigator;
- Presence of active gastrointestinal diseases like active gastric and duodenal
ulcers, ulcerative colitis, or unremoved tumors with active bleeding, or other
conditions judged by the investigator to possibly cause gastrointestinal bleeding or
perforation;
- Evidence or history of significant bleeding tendency or episodes within 3 months
before enrollment (bleeding >30 mL, hematemesis, melena, or hematochezia),
hemoptysis (> 5 mL of fresh blood within 4 weeks), or thromboembolic events such as
stroke and/or transient ischemic attack within 12 months;
- Any severe and/or uncontrollable disease, including:
1. History or presence of interstitial lung disease, pneumoconiosis, radiation
pneumonitis, drug-related pneumonitis, severely impaired lung function, or
other conditions that may interfere with the detection and management of
suspected drug-related pulmonary toxicity.
2. Clinically significant history of liver diseases, including active hepatitis
(Hepatitis B reference: HBsAg positive with HBV DNA > 1 x 10^4 copies/mL or >
2000 IU/mL; Hepatitis C reference: HCV antibody positive with HCV RNA > 1 x
10^3 copies/mL), or other hepatitis, clinically significant moderate to severe
hepatic cirrhosis; Note: Participants with eligible Hepatitis B or C must
receive continuous antiviral treatment to prevent viral reactivation.
3. Human immunodeficiency virus (HIV) antibody positivity.
4. Uncontrolled hypertension (defined as systolic blood pressure ≥ 140 mmHg and/or
diastolic blood pressure ≥ 90 mmHg not controlled by medications);
5. Poorly controlled cardiovascular clinical symptoms or diseases, including but
not limited to acute myocardial infarction, malignant arrhythmias (including
QTc > 450 ms for males and > 470 ms for females), ≥ Grade II congestive heart
failure (New York Heart Association (NYHA) classification), or clinically
significant abnormal myocardial enzyme levels as determined by the
investigator;
6. Active or uncontrollable severe infections (≥ NCI-CTC AE Grade 2 infections);
7. Poorly controlled diabetes (fasting blood glucose (FBG) > 10 mmol/L);
8. Proteinuria ≥ ++ on urinalysis and confirmed 24-hour urinary protein > 1.0 g;
9. History or presence of autoimmune diseases, including but not limited to
Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis,
Wegener's granulomatosis, Graves' disease, rheumatoid arthritis, hypophysitis,
uveitis, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis,
autoimmune vasculitis, or autoimmune neuropathies (e.g., Guillain-Barre
syndrome). Exceptions include stable hypothyroidism requiring hormone
replacement therapy (including hypothyroidism due to autoimmune thyroid
disease), psoriasis or vitiligo not requiring systemic treatment;
- Pregnant or breastfeeding women;
- Known history of allergy to investigational drug components;
- Participation in other clinical trials and treatment with investigational drugs
within 4 weeks before enrollment;
- Any disease or condition that affects drug absorption or the inability of
participants to take oral medications;
- Any other conditions judged by the investigator to be unsuitable for enrollment,
including diseases, metabolic disorders, abnormal physical examination, laboratory
result abnormalities, or any other conditions affecting the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Renji hospital
Address:
City:
Shanghai
Zip:
200127
Country:
China
Start date:
October 30, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
RenJi Hospital
Agency class:
Other
Collaborator:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
RenJi Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06621095
