A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, open-label, randomized, phase 2/3 trial of the bispecific antibody CTX-009 plus paclitaxel versus paclitaxel in patients with previously treated, unresectable advanced or metastatic biliary tract cancers.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Compass Therapeutics
• Treatments: Paclitaxel

Criteria

Inclusion Criteria

1. 18 years of age or older

2. Histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma)

3. Patients who experienced progressive disease or relapse after receiving first-line therapy with a regimen that included gemcitabine in combination with a platinum agent. Patients who received two or more systemic anticancer therapies are excluded from enrollment.

4. At least one lesion measurable as defined by RECIST v1.1

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

6. Predicted life expectancy of at least 12 weeks

7. No evidence of ongoing infection and adequate biliary excretion or patients whose adequate biliary excretion can be confirmed with the following procedures:

1. Patients who underwent endoscopic retrograde biliary drainage (ERBD) at least 1 week before the investigational drug treatment

2. Patients who underwent percutaneous transhepatic biliary drainage (PTBD) at least 4 weeks before the investigational drug treatment

3. Patients free of any signs of active or suspected uncontrolled infection after a drainage procedure

4. Patients free of any risk of hemorrhage and with incision completely healed

8. Adequate bone marrow, hepatic, and renal function within 14 days of randomization as described below. (Patient must be free of granulocyte colony-stimulating factor (G-CSF) treatment and blood transfusion within 14 days prior to the lab test):

1. Absolute neutrophil count (ANC) ≥ 1,500/mm3

2. Hemoglobin ≥ 9.0 g/dL

3. Platelet count ≥ 100,000/mm3

4. White Blood Cell ≥ 3,000/mm3

5. Total bilirubin ≤ 1.5 X Upper Limit of Normal (ULN)

6. Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ≤ 3.0 X ULN (≤5 x ULN in case of hepatic metastasis)

7. Serum Creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault

8. Urine protein ≤ 1+ by Dipstick (Only when urinalysis shows a protein dipstick result of > 1 positive (+), the total protein volume (<1.0 g/24hr) can be confirmed with a 24-hour urine test.)

9. Serum amylase and lipase level ≤ 1.5 X ULN

10. Serum Albumin ≥ 3.0 g/dL

9. Female patients who are women of childbearing potential (WCBP) must have a negative pregnancy test (serum-human chorionic gonadotropin (hCG) or urine-hCG performed at the Investigator's discretion) within 14 days of randomization

10. Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commit to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment.

11. Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before any protocol-directed screening procedures are performed

Exclusion Criteria

1. From the time point of screening,

1. Less than 4 weeks have elapsed since patients had a surgery or major procedure

2. Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy

2. Prior to the initial treatment of study drug,

1. Less than 2 weeks have elapsed since patients had chemotherapy or hormone therapy (However, patients cannot participate when nitrosoureas or mitomycin was administered within 6 weeks)

2. Less than 4 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment

3. Less than 6 weeks since cryotherapy, radiofrequency ablation, anhydrous alcohol therapy, or photodynamic therapy

3. A history of the following cardiovascular diseases in past 5 years:

1. Congestive heart failure (CHF) that corresponds to Class II or a higher class (or less than 50% of left ventricular ejection fraction (LVEF)) under New York Heart Association (NYHA) classification

2. Uncontrolled hypertension (Systolic/Diastolic Blood Pressure (SBP/DBP) >140/90 mmHg) (e.g., patient with SBP/DBP >140/90 mmHg despite the best care including anti-hypertensive medications)

3. Patients with any history of hypertensive crisis or pre-existing hypertensive encephalopathy

4. Pulmonary hypertension

5. Myocardial infarction

6. Uncontrolled arrhythmia

7. Unstable angina

8. Patients with any significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to the initial treatment of the investigational product

4. History of hypersensitivity reactions to any components of the investigational product or other drugs of the same class (humanized/human monoclonal antibody drugs) or paclitaxel

5. Patients with contraindications to paclitaxel therapy

6. Patients with persistent, clinically significant toxicities (excluding hair loss) from previous anticancer treatment that corresponds to Grade 2 or a higher grade under NCI-CTCAE v5.0

7. Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis can participate provided that systemic corticosteroid treatment was discontinued at least 4 weeks prior to screening and that the patient is radiologically and neurologically stable or improving)

8. A history of the following hemorrhage-related or gastroenterological disease:

1. Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor in great arteries

2. History of clinically significant gastroenterological disease, such as peptic ulcer, GI bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms, and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease (IBD)

9. Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant drugs (warfarin, heparin, etc.) within 2 weeks prior to screening, or is expected to need those drugs during the clinical study

10. Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted):

1. NSAIDs: Up to 3 consecutive days' use is permitted.

2. Corticosteroids: Topical use of corticosteroids, such as topical intra-articular injection, intranasal administration, eye drops, inhaler, etc., or temporary systemic corticosteroid use for treatment and prevention of patient's contrast media allergy, paclitaxel pre-treatment, or adverse event, is permitted

11. Severe infection requiring systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases

12. Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Inactive hepatitis B carriers who tested HBsAg positive may enroll, provided that the patient's liver function values are normal. Also, patients with chronic HBV infection which has been controlled by the site's treatment guideline may enroll. HCV patients showing sustained viral response or patients with immunity to HBV infection may enroll.

13. Patients with other severe diseases or uncontrolled illnesses that warrant the exclusion from the study (permitted only if medically controlled) including but not limited to:

1. Pre-existing condition of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to screening

2. Major, unhealed injury, active ulcer, or untreated fracture

3. Pre-existing conditions of cerebrovascular incident (ischemic or hemorrhagic stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months prior to screening.

4. Moderate to severe ascites and/or pleural effusion. However, enrollment is permitted for patients with ascitic fluid as long as paracentesis is not required to improve the condition.

5. Interstitial lung disease or pulmonary fibrosis

14. Patients expected to require anticancer treatment other than the investigational product during the clinical study

15. Pregnant or lactating patients, or patients planning to become pregnant during the clinical study

16. A history of primary malignant tumor other than biliary tract cancer with the following exceptions:

1. At least 3 years have passed since complete remission of primary malignant tumor (Patients who had papillary thyroid carcinoma and underwent a radical resection may participate in the clinical study even if less than 3 years have elapsed).

2. At least 1 year has passed since complete resection of dermal basal cell carcinoma or successful treatment of cervical intraepithelial neoplasia

17. Clinically significant abnormal ECG findings or history determined as clinically significant by the Investigator

18. QT interval (Fridericia's formula) (QTcF) interval > 450msec at the time of screening

19. Patients who took a drug known to extend QT intervals within 14 days or within 5 times of half-life of drug, whichever is shorter, before the initial investigational product treatment.

20. Any condition (psychological, geographical, physical, etc.) that does not permit compliance with the protocol