A Phase I Study of Ceritinib (LDK378), a Novel ALK Inhibitor, in Combination With Gemcitabine-Based Chemotherapy in Patients With Advanced Solid Tumors

Status: Completed
Location: See location...
Intervention Type: Drug, Other
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This phase I trial studies the side effects and best dose of ceritinib and combination chemotherapy in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Ceritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ceritinib and more than one drug (combination chemotherapy) may be a better treatment for solid tumors or pancreatic cancer.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Arm 1: histologically or cytologically confirmed solid tumors that are advanced that gemcitabine-based treatment is considered a clinically appropriate option

• Arm 2: histologically or cytologically confirmed adenocarcinoma of the pancreas that is locally advanced or metastatic

• Arm 3: histologically or cytologically confirmed solid tumors that are advanced that gemcitabine plus cisplatin treatment is considered a clinically appropriate option

• Arms 1E, 2E and 3E: solid tumor that demonstrate anaplastic lymphoma kinase (ALK) positivity; ALK positivity can be assessed using the assays below, and documentation of ALK positivity using one of the tests below is required

‣ Fluorescence in situ hybridization (FISH) test for ALK positivity using the Food and Drug Administration (FDA)-approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); OR

⁃ Harboring a confirmed ALK positivity, as determined by positivity to the Ventana immunohistochemistry (IHC) assay

• Arms 1E: previously treated with and progressed on gemcitabine-containing therapy

• Arms 1, 2, 3: patients should have clinically measurable or evaluable malignant disease

• Arms 1E, 2E, 3E: patients with at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 that have not been previously irradiated

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1

• Life expectancy \>= 3 months

• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (system international \[SI\] units 1.5 x 10\^9/L)

• Platelets \>= 100,000 cells/mm\^3 (SI units 100 x 10\^9/L)

• Hemoglobin \>= 9 g/dL (SI units 90 g/L) (in the absence of transfusion within 24 hours prior to dosing)

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 3 x upper limit of normal (ULN); in patients with known hepatic involvement, AST and ALT =\< 5 x ULN are allowed

• Total bilirubin =\< 1.5 x ULN

• Calculated or measured creatinine clearance (CrCL) \>= 60 mL/min using modified Cockcroft and Gault formula

• Serum lipase =\< 2 x ULN

• Serum amylase =\< 2 x ULN

• International normalized ratio (INR) =\< 1.5; (anticoagulation is allowed if target INR =\< 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight \[LMW\] heparin for \> 2 weeks at the first dose of study agent)

• If urinalysis shows proteinuria, 24 hour urine collection is to be performed and the 24 hour urine protein is to be \< 2 grams to be eligible

• Willing and able to comply with scheduled visits, treatment plan and laboratory tests

• Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures

• Patient must consent to the use of their archival tumor tissue for protocol use if available

Locations
United States
New York
Roswell Park Cancer Institute
Buffalo
Time Frame
Start Date: 2015-01-08
Completion Date: 2019-02-12
Participants
Target number of participants: 38
Treatments
Experimental: Arm 1 (ceritinib MTD then with gemcitabine alone)
Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine hydrochloride-based therapy is clinically appropriate receive ceritinib PO (QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors who previously progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Related Therapeutic Areas
Sponsors
Leads: Roswell Park Cancer Institute
Collaborators: Novartis

This content was sourced from clinicaltrials.gov