Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Patients with HER2+ metastatic or unresectable adenocarcinoma of the esophagus, gastroesophageal junction or stomach will receive trastuzumab and mFOLFOX-6 in combination with KD019 to evaluate the safety, toxicity and MTD of this regimen. There will be four dose cohorts for KD019. KD019 will be administered orally continuously daily on a 28 day cycle. Trastuzumab and mFOLFOX-6 will be administered as infusions every 2 weeks at standard doses without escalation. The sequence on the days when all agents are administered will be KD019 followed by trastuzumab and mFOLFOX-6.

KD019

Jennifer Wu, MD

This dose-escalation study is to determine the safety, maximum tolerated dose (MTD) and efficacy of KD019 in combination with trastuzumab and mFOLFOX-6.

This is an open-label, single-arm, dose-escalation phase Ib study to determine the safety, maximum tolerated dose (MTD) and efficacy of KD019, a multi kinase inhibitor of EGFR, HER2, Src and VEGFR2, in combination with trastuzumab and mFOLFOX-6 for patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic or unresectable adenocarcinoma of esophagus, gastroesophageal junction or stomach.

Patients with HER2+ metastatic or unresectable adenocarcinoma of the esophagus, gastroesophageal junction or stomach will receive trastuzumab and mFOLFOX-6 in combination with KD019 to evaluate the safety, toxicity and maximum tolerated dose of this regimen. There will be four dose cohorts for KD019. KD019 will be administered orally continuously daily on a 28 day cycle. Trastuzumab and mFOLFOX-6 will be administered as infusions every 2 weeks at standard doses without escalation. The sequence on the days when all agents are administered will be KD019 followed by trastuzumab and mFOLFOX-6.

Hypothesis A) KD019, a small molecule inhibitor of multiple receptor tyrosine kinases including EGFR, HER2, VEGFR-2 and Src, can be safely added, in an effective dose, to the every 2 week schedule of mFOLFOX-6 + trastuzumab for patients with metastatic or unresectable HER2+ adenocarcinoma of esophagus, GEJ or stomach

B) When added to mFOLFOX-6 + trastuzumab, KD019will increase response duration, progression free survival

Primary objective:

To assess the safety, tolerability, maximum tolerated dose (MTD), recommended phase II dosing (RP2D) of KD019 in combination of trastuzumab and mFOLFOX-6

Secondary objectives:

1. To characterize the pharmacokinetics (PK) parameters of KD019 administered once daily in combination with every 2 week mFOLFOX-6 and trastuzumab in subjects with metastatic or unresectable HER2+ adenocarcinoma of the esophagus, gastroesophageal junction (GEJ) and stomach.
2. To evaluate tumor biopsy specimens pre- and post- treatment with KD019 and trastuzumab for changes in target receptors and correlate with response

KD019 and Trastuzumab in Patients With Esophagus, Gastroesophageal Junction and Stomach Cancer

A Phase Ib Study of KD019 Plus Trastuzumab in Patients With HER2 Overexpressed or Amplified Metastatic or Unresectable Adenocarcinoma of Esophagus, Gastroesophageal Junction and Stomach

To determine maximum tolerated dose (MTD) and RP2D of KD019 in combination with trastuzumab and mFOLFOX-6 when given to patients with HER2+ metastatic or unresectable adenocarcinoma of the esophagus, GEJ or stomach (gastric).

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Tumor assessments will be performed using RECIST criteria (Version 1.1). Imaging scans may be done within 4 weeks prior to the first dose of study drug (baseline) and then every 12 weeks (±7 days) after the first dose of study drug until documented progression. Responses will be confirmed by repeat assessments between 28 and 35 days after the response criteria are first met.

Overall response rates are defined as partial response plus complete response. Tumor response will be based on Response evaluation Criteria in Solid Tumors (RECIST 1.1). Response rates will be estimated with exact 95% confidence intervals for each dose level. Kaplan Meier curves will be used to summarize progression free survival.

The duration of overall response is measured from the time measurement are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Tumor response will be based on Response evaluation Criteria in Solid Tumors (RECIST 1.1).

Clinical benefit rate is defined as complete response plus partial response plus stable disease \>16 weeks, and will be summarized descriptively. Tumor response will be based on Response evaluation Criteria in Solid Tumors (RECIST 1.1).

Patients will undergo pharmacokinetics at the following time points:

* Pre- 15 minutes pre-dosing: C1 D1, C1 D15 and then D1 only starting cycle 2 and thereafter Up to and including the cycle 6 visit.
* Post- at 1 hour, 2 hours, and 4-6 hours post dosing: C1 D1, C1 D15 and 4-6 hours post dosing only on D1 only starting cycle 2 .
* A PK sample will also be drawn if QTc(f) interval increases to an absolute value of \>500 msec. The concentration of KD019 in these samples will be used to confirm exposure to KD019 and to further characterize the plasma PK of KD019 in this subject population.
* 30 days post treatment visit.

NYU Langone Health

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Disease Progression

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Amino Acids

Erlotinib Hydrochloride

XL647

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

KD019 will be administered orally once daily at a dose of 300 mg. One dose reduction to 200 mg will be permitted.

Erlotinib will be administered orally once daily at a dose of 150 mg. One dose reduction to 100 mg daily will be permitted.

Erlotinib

This study involves treatment with KD019 or erlotinib in patients with Non-small cell lung cancer (NSCLC) who have progressed after first- or second- line chemotherapy. It is hypothesized that KD019 can prolong survival compared with erlotinib.

KD019 Versus Erlotinib in Subjects With Stage IIIB/IV Non Small Cell Lung Cancer With Progression After First- or Second-Line Chemotherapy

A Multi-Center, Phase 3, Double-Blind, Randomized, and Controlled Trial of KD019 vs Erlotinib in Subjects With Stage IIIB/IV Non-Small Cell Lung Cancer Who Have Progressed After First- or Second-Line Chemotherapy

For the purpose of data collection, all untoward events that occur after informed consent through 30 days after last dose of study treatment are to be recorded.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
KD019 and Trastuzumab in Patients With Esophagus, Gastroesophageal Junction and Stomach Cancer	NCT02205463	Esophageal Canc... Stomach Cancer	KD019	18 Years -	NYU Langone Health
KD019 and Trastuzumab in Patients With Esophagus, Gastroesophageal Junction and Stomach Cancer	NCT02205463	Esophageal Canc... Stomach Cancer	KD019	18 Years -	NYU Langone Health
KD019 Versus Erlotinib in Subjects With Stage IIIB/IV Non Small Cell Lung Cancer With Progression After First- or Second-Line Chemotherapy	NCT01487174	Carcinoma, Non-...	KD019 Erlotinib	18 Years -	Kadmon Corporation, LLC

Spots Global Cancer Trial Database for kd019

Every month we try and update this database with for kd019 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for kd019

Every month we try and update this database with for kd019 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for kd019 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.