SHS_492335 GOLP CAGI 16099

A Phase II, Multicenter, Single-Arm Study of Oral Ceritinib in Adult Patients With ALK-Activated Gastrointestinal Malignancies

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

Select Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of inoperable colorectal adenocarcinoma, pancreatic, hepatocellular, cholangiocarcinoma, small bowel, gastric or esophageal adenocarcinoma that carries an activated ALK pathway.
Age 18 years or older at the time of informed consent.
Received at least 1 line of cytotoxic chemotherapy.
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.
Recovered from all toxicities related to prior anticancer therapies to grade ≤ 2 (CTCAE v 4.03).
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 in protocol.
Adequate renal function as defined in protocol.
Adequate hepatic function as defined in the protocol.
Serum amylase ≤ 2 x ULN and serum lipase ≤ 1 x ULN
Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L)
Patient must have various normal laboratory values as defined in protocol.

Select Exclusion Criteria:

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.
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 inhibitor agents.
Currently receiving treatment with warfarin sodium (Coumadin) or any other coumarin-derivative anti-coagulants. Anti-coagulants not derived from warfarin are allowed
Symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry.
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.
Known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease.
Certain cardiac conditions as defined in the protocol.
Uncontrolled hypertension with or without anti-hypertensive medication.
Receiving certain medications that meet one of the following criteria outlined in the protocol and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation (details in protocol).
Unstable or increasing doses of corticosteroids.
Enzyme-inducing anti-convulsive agents.
Herbal supplements.
Uncontrolled intercurrent illness as listed in protocol.
Major surgical procedure, open biopsy, or significant traumatic injury less than 4 weeks from first dose of first study drug administration.
Known inability to swallow up to five LDK378 capsules daily.
Phase II
Philip Gold, M.D.
AGICC (Academic GI Cancer Consortium)
Andrew Bathan
  • Swedish Medical Center