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Tree Topp

ClinicalTrials.gov Identifier

NCT03093870

Principal Investigator

Dr. Madappa Kundranda

Principal Investigator Phone

(602)256-6444

Principal Investigator Email

Madappa.Kundranda@bannerhealth.com

Additional Study Coordinators

Charlotte, North Carolina - Levine Cancer Institute, Carolinas Healthcare System 1021 Morehead Medical Dr.  Charlotte, NC  28204; (980) 442-2000 Contact: Study Coordinator - Melani Terry, (980)-442-2157, Melani.Terry@atriumhealth.org Dallas, Texas -  Texas Oncology, P.A., Texas Oncology Sammons Cancer Center 3410 Worth Street, Suite 730 , Dallas, TX   75246; (214)-370-1000; www.texasoncology.com. Contact: Study Coordinator -Catinna Mallett, (214)-370-1949, Catinna.Mallett@usoncology.com Detroit, Michigan - Karmanos Cancer Institute/Wayne State University, Karmanos Cancer Center 4100 John R MM00RA Detroit, MI 48201; 1-800-527-6266; www.karmanos.org Contact: info@karmanos.org Gilbert, Arizona - Banner MD Anderson Cancer Center 2946 E. Banner Gateway Dr., Ste. 450, Gilbert, AZ 85234; (480) 256-6444 Contact: Dr. Madappa Kundranda, (602)256-6444; Madappa.Kundranda@bannerhealth.com. Study Coordinator - Jana Bergelin; (480)256-5168; Jana.Bergelin@bannerhealth.com Las Vegas, Nevada – CCCN 3730 So. Eastern Ave, Suite 202, Las Vegas, NV 89169; (702) 952-3400 Contact: Principal Investigator – Dr. Fadi Braiteh, (702)952-3400; fadi.braiteh@usoncology.com Study Coordinator – Melissa Vicuna, (702)968-3880; CCCN.Referrals@usoncology.com

Study Overview

The study drug, varlitinib, is an investigational anti-tumor product, delivered in the form of tablets. The study drug has been administered as a single and combination treatment to patients with metastatic gastric cancer, gastro-esophageal tumors, breast cancer, and biliary tract cancer (BTC). Laboratory studies and animal research suggest that the study drug stops cancer cells from growing by affecting different kinds of proteins in cancer cells. In particular, laboratory studies suggest that the study drug may be effective in targeting and inhibiting (preventing) the pathways of certain proteins in cells called “HER” (human epidermal growth factor receptor). The “HER” protein is important in types of cancer such as cholangiocarcinoma (BTC), gastric cancer, breast cancer, and others. Varlitinib has shown activity in BTC. In this study, patients will receive study drug plus capecitabine, or placebo plus capecitabine. Inclusion allows all forms of BTC and there is no biomarker-based patient selection.

Enrollment Information

Actively Recruiting

Study Start Date

20170704

Study End Date

20191231

Study Purpose

Both Part 1 & Part 2 assess the efficacy and safety of Varlitinib with Capecitabine in BTC

Inclusion Criteria

Are of or older than the legal age in the respective countries at the time when written informed consent is obtained Have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma (CCA), gallbladder cancer and carcinoma of Ampulla of Vater. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma. Have received and failed one and only one prior line of systemic treatment for advanced or metastatic disease with radiologic evidence of disease progression. This prior line of systemic treatment must also contain gemcitabine Have received at least 6 doses of gemcitabine containing treatment in first line (Adjuvant therapy is not regarded as 1st line therapy) Have radiographically measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by Independent Central Review (ICR) (For Part 1) Have no evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below or equal to 1.5 × upper level of normal (ULN) Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Are able to understand and willing to sign the informed consent form Have adequate organ and hematological function: Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelet count ≥ 100 × 109/L Renal functions, as follows: Estimated glomerular filtration rate or creatinine clearance > 50 mL/min/1.73m2 Hepatic function, as follows: Albumin ≥ 3 g/dL Total bilirubin ≤ 1.5 × ULN Aspartate aminotransferase and alanine aminotransferase ≤ 5 × ULN

Exclusion Criteria

Are currently on or have received anti-cancer therapy within the past 3 weeks before receiving the first dose of study medication Are currently on or have received radiation or local treatment within the past 3 weeks for the target lesion(s) before receiving the first dose of study medication Have evidence of multiple (≥ 2) peritoneal metastases or ascites at baseline as assessed by ICR (For Part 1). (Ascites which can be attributed by non-malignant causes is not excluded.) Have had major surgical procedures within 14 days prior to first dose of study medication Have a known metastatic brain lesion(s), including asymptomatic and well controlled lesion(s) Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications which in the opinion of the Investigator could jeopardize the validity of the study results Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements Have any history of other malignancy unless in remission for more than 1 year (non-melanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary) Are female patients who are pregnant or breast feeding Have been previously treated with varlitinib or have been previously treated with capecitabine as first line therapy for advanced or metastatic disease. For patients who have previously received capecitabine as a radiosensitizer or as part of their adjuvant therapy and their disease has relapsed for more than 6 months after their last dose of capecitabine adjuvant therapy, their capecitabine therapy will not be considered as a line of systemic chemotherapy for metastatic/advanced disease, and thus they can participate in the study Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication Have unresolved or unstable serious toxicity (≥ common terminology criteria for adverse events 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior cancer treatment Have a known positive test for human immunodeficiency virus, hepatitis C (treatment naïve or after treatment without sustained virologic response), or hepatitis B infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL Have a known history of drug addiction within last 1 year which, in the opinion of the Investigator, could increase the risk of non-compliance to investigational product Need continuous treatment with proton pump inhibitors during the study period Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or have a history of interstitial lung disease or current interstitial lung disease REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT Doctor’s visit Blood test Urine analysis CT or MRI scan

Potential Side Effects

fatigue (tiredness) diarrhea nausea anorexia (loss of appetite) skin rashes vomiting dry skin increased liver enzymes - ALT / AST (indicating possible liver inflammation or damage)

Financial Assistance Available

No