Phase II Study of Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients with Advanced or Metastatic Cholangiocarcinoma

Phase 1

• Conditions: Advanced or metastatic cholangiocarcinoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-002066-24-AT
• Lead Sponsor: The All Ireland Cooperative Oncology Research Group (ICORG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-20
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Patients must have a histologically-confirmed diagnosis of cholangiocarcinoma American Joint Committee on Cancer (AJCC) Stage II, III, or IV CCA (intra-hepatic, extra-hepatic and perihilar) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed histology are not allowed.
2. Must have radiographically measurable disease (RECIST Version 1.1) in at least one site not previously treated with radiation, chemoembolization, radioembolization, or other local ablative procedures (i.e. must have at least one measurable target lesion, either within the liver or in a measurable metastatic site); a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a Radiologist, is acceptable. Appropriate imaging should have been completed = 4 weeks prior to registration.
3. May have received prior radiation, chemoembolization, radioembolization, or other local ablative therapies, or hepatic resection if completed = 4 weeks prior to registration AND if patient has recovered to = grade 1 toxicity.
NOTE: Measurable disease (as required above) must still be present.
4. May have received prior radiation for bone or brain metastases if patient is now asymptomatic and has completed all radiation and steroid therapy (if applicable) = 2 weeks prior to registration.
5. Age = 18 years.
6. Child-Pugh score of A or B with = 7 points (Appendix I of protocol).
7. ECOG performance status of 0-1 (Appendix II) of protocol).
8. Ability to understand and willingness to sign IRB-approved informed consent.
9. Willing to provide archived tissue, if available, from a previous diagnostic biopsy.
10. Must be able to tolerate CT and/or MRI with contrast.
11. Adequate organ function as measured by the following criteria, obtained = 2 weeks prior to registration:
• Absolute Neutrophil Count (ANC) = 1500/mm3
• Hemoglobin ?9.0 g/dL
• Platelets ?100,000/mm3
• Serum Creatinine = 1.5x Upper Limit Normal (ULN)
• Creatinine Clearance = 50 mL/min
• Albumin = 2.8 g/dL
• Total Bilirubin = 1.5 mg/dL or = 1.5x ULN
• AST/ALT = 2.5x ULN (= 5x ULN in patients with liver metastases)
• INR <1.5x the ULN [INR = 1.5 is allowed if anticoagulation is used. Patient must be on a stable dose of anticoagulant (i.e. Coumadin) for = 2 weeks at time of randomization.]

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

1. Women must not be pregnant or breastfeeding since nab-paclitaxel and/or gemcitabine may harm the fetus or child. All females of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 2 weeks prior to registration.
2. Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 3 months following completion of study therapy. Method of contraception must be documented.
NOTE: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
3. Must not have received prior systemic cytotoxic chemotherapy or targeted therapy for this cancer.
NOTE: Prior systemic cytotoxic therapy for other diagnoses is permitted if the last dose was >6 months prior, any prior toxicity has recovered to = grade 1, and treatment was not discontinued for toxicity.
4. Must not be receiving treatment with other investigational agents and must not have received any other investigational agent’s = 4 weeks prior to registration.
5. Must not have a pre-existing >grade 2 peripheral neuropathy.
6. Must not be receiving immunosuppressive medications, including systemic corticosteroids, aside from the following exceptions: used for adrenal replacement, appetite stimulation, acute therapy for asthma or bronchitis exacerbation (= 2 weeks), or anti-emesis.
7. No known Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) seropositivity. The risk for potential toxicities secondary to Hepatitis B, Hepatitis C or HIV (e.g., increased risk for fatal opportunistic infection) may confound the toxicity profile of the chemotherapy regimen. Testing is not required in absence of clinical suspicion.
8. Must not have undergone liver transplantation.
9. Must not have symptomatic brain or bone metastases (Section 3.4 for additional requirements).
10. Must not have serious non-healing wound, ulcer, bone fracture, or abscess.
11. Must not have undergone a major surgical procedure <4 weeks prior to registration.
12. Must not have possible histories of pneumonitis or pneumonitis risk factors (Section 5.3.5).
13. Must not have an active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.
NOTE: Patients with history of malignancy are not considered to have a currently active” malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse.
14. Must have no ongoing or active, uncontrolled infections (afebrile for = 48 hours off antibiotics).
15. Must have no evidence of significant, uncontrolled concomitant diseases including, but not limited to: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction within preceding 12 months, uncontrolled peripheral vascular disease, cerebrovascular accident within preceding 12 months, pulmonary disease impairing functional status or requiring oxygen, connective tissue disease including lupus.
16. Must not have any history of allergic reaction(s) attributed to compounds of similar composition to nab-paclitaxel or gemcitabine.
17. Must not require prohibited medications with the potential for serious interactions with protocol therapy, and wh

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified