Ceritinib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors or Locally Advanced or Metastatic Pancreatic Cancer

Advanced Malignant Solid Neoplasm Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of ceritinib in combination with gemcitabine (gemcitabine hydrochloride) alone, gemcitabine/nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and gemcitabine/cisplatin in patients with advanced solid malignancies.

SECONDARY OBJECTIVES:

I. Characterize the safety profile of ceritinib in combination with gemcitabine based chemotherapy in advanced solid malignancies.

II. Determine the pharmacokinetic profile of ceritinib, gemcitabine, nab-paclitaxel, cisplatin and their metabolites when administered in combination in patients with advanced solid tumors.

III. Determine the preliminary efficacy of the study combinations.

TERTIARY OBJECTIVES:

I. Explore potential biomarkers of efficacy to the study combination.

OUTLINE: This is a dose-escalation study of ceritinib. Patients are assigned to 1 of 3 treatment arms.

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 orally (PO) once daily (QD) on days 1-28 and gemcitabine hydrochloride intravenously (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 anaplastic lymphoma kinase positive (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.

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.

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.

After completion of study treatment, patients are followed up for at least 4 weeks. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• ALK Positive
• Metastatic Pancreatic Adenocarcinoma
• Pancreatic Neoplasms
• Stage III Pancreatic Cancer
• Stage IV Pancreatic Cancer

• NCT number: NCT02227940
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Completed
• Phase: Phase 1
• Start date: January 8, 2015
• Completion date: February 12, 2019