Study of Oral Ceritinib in Patients With ALK and ROS1 Activated Gastrointestinal Malignancies

NCT02638909 | Terminated Phase 2 DMC

• 1 other identifier: NOV-ALK-01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 6

Brief Summary

The available data indicate that Ceritinib has substantial anti-tumor activity in patients with anaplastic lymphoma kinase (ALK) and ROS1 rearranged non-small cell lung cancer (NSCLC). This trial will investigate the potential of Ceritinib in patients with advanced gastrointestinal malignancies with ALK and ROA1 rearrangement, and for whom there is no available therapeutic option.

Conditions

Colorectal Adenocarcinoma; Cholangiocarcinoma; Pancreatic Adenocarcinoma; Hepatocellular Adenocarcinoma; Gastric Adenocarcinoma; Esophageal Adenocarcinoma

Keywords

Gastrointestinal malignancies

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) of ceritinib, as defined as the percentage of patients who have achieved complete response, partial response, and stable disease at 2 months per RECIST 1.1) to ceritinib by investigator assessment

  2 months

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  20 months

• Objective tumor response based on computed tomography scans (or magnetic resonance imaging if patients are allergic to iodinated contrast) per RECIST 1.1 criteria

  2 months

Study Arms (1)

ceritinib

EXPERIMENTAL

Phase II, single-arm study of oral ceritinib in adult patients with ALK and ROS1 activated gastrointestinal malignancies

Drug: ceritinib

Interventions

ceritinib DRUG

Treatment with ceritinib will continue until patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anticancer therapy and/or dies.

Also known as: Zykadia

ceritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of inoperable colorectal adenocarcinoma, pancreatic, hepatocellular, cholangiocarcinoma, small bowel, gastric or esophageal adenocarcinoma that carries an activated ALK or ROS1 pathway
• Age 18 years or older at the time of informed consent.
• Patients must have received at least 1 line of cytotoxic chemotherapy
• Patients must have archival tissue sample available, collected either at the time of diagnosis or any time since.
• \- If archival tissue is unavailable, patient must be eligible and willing to undergo a fresh tissue biopsy
• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2 (CTCAE v 4.03) provided that concomitant medication is given prior to initiation of treatment with LDK378, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study. Additionally, patients with any grade of alopecia are allowed on treatment.
• Cohort Expansion Phase: Patient must have measurable lesions as defined by RECIST version 1.1 criteria.
• ECOG performance status 0-2
• Patients must have normal organ and marrow function as defined below: Bone marrow function defined as the following: An absolute neutrophil count ≥ (ANC) 1,500/mcl. Platelets ≥ 75,000/mcl. Hemoglobin ≥ 8 g/dl.
• Renal function defined as the following: Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN). Calculated or measured creatinine clearance (CrCL) ≥ 30 mL/min
• Hepatic function defined as the following: Serum total bilirubin \< 1.5 x ULN. AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 3.0 x ULN. Serum albumin ≥ 2.5 g/dl. If liver involvement, AST, ALT, and alkaline phosphatase ≤ 5.0 x ULN.
• Serum amylase ≤ 2 x ULN and serum lipase ≤ 1 x ULN
• Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L)
• Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:
• Potassium ≥ lower limit of normal (LLN)

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (4 weeks for radiotherapy to the lung fields and 6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
• Prior therapy with ceritinib or other ALK or ROS1 inhibitor agents
• Patients who are currently receiving treatment with warfarin sodium (Coumadin®) or any other coumarin-derivative anti-coagulants.
• Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms.
• Impairment of GI function or GI disease that may significantly alter the absorption of ceritinib
• History of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
• Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
• Cardiac conditions as follows:
• Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 6 months prior to first study drug administration.
• Class II-IV New York Heart Association (NYHA) congestive heart failure.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• QTc (Frederica) prolongation \> 470 msec.
• Subjects with valvular heart disease CTCAE (Version 4.0) Grade 2.
• Known left ventricular ejection fraction (LVEF) \< 50%.

Sponsors & Collaborators

• Criterium, Inc.: lead
• University of Colorado, Denver: collaborator
• Novartis: collaborator

Study Sites (6)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Laura & Isaac Permutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

The Ohio State University, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Adenocarcinoma Of Esophagus

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Christopher Lieu, MD

  Criterium Inc., d.b.a. Academic GI Cancer Consortium (AGICC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 23, 2015
• Study Start: December 1, 2015
• Primary Completion: March 29, 2018
• Study Completion: March 29, 2018
• Last Updated: April 2, 2018

Record last verified: 2018-03

Locations

US (6)