KD019 and Trastuzumab in Patients With Esophagus, Gastroesophageal Junction and Stomach Cancer
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|ClinicalTrials.gov Identifier: NCT02205463|
Recruitment Status : Withdrawn (IND application withdrawn)
First Posted : July 31, 2014
Last Update Posted : August 1, 2014
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer Stomach Cancer||Drug: KD019||Phase 1|
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
To assess the safety, tolerability, maximum tolerated dose (MTD), recommended phase II dosing (RP2D) of KD019 in combination of trastuzumab and mFOLFOX-6
- 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.
- To evaluate tumor biopsy specimens pre- and post- treatment with KD019 and trastuzumab for changes in target receptors and correlate with response
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||December 2014|
|Estimated Primary Completion Date :||July 2017|
|Estimated Study Completion Date :||July 2017|
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.
- Maximum Tolerated Dose (MTD) [ Time Frame: 28 Days ]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 [ Time Frame: 3 Years ]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.
- Objective Response Rate [ Time Frame: 3 Years ]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.
- Duration of Response [ Time Frame: 3 Years ]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 [ Time Frame: 3 Years ]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).
- Pharmacokinetics of KD019 [ Time Frame: Multiple ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205463
|United States, New York|
|NYU Langone Medical Center|
|New York, New York, United States, 10016|
|Principal Investigator:||Jennifer Wu, MD||NYU Langone Medical Center|