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

NCT02205463 | Withdrawn Phase 1 DMC

• 1 other identifier: s14-01171
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Esophageal Cancer; Stomach Cancer

Keywords

Esophagus; Gastroesophageal Junction; Stomach; Gastric; Cancer; HER2; Metastatic; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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).

  28 Days

Secondary Outcomes (5)

• Progression-Free Survival

  3 Years

• Objective Response Rate

  3 Years

• Duration of Response

  3 Years

• Clinical Benefit Rate

  3 Years

• Pharmacokinetics of KD019

  Multiple

Study Arms (1)

KD019

EXPERIMENTAL

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.

Drug: KD019

Interventions

KD019 DRUG

KD019

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of adenocarcinoma of stomach, GEJ or esophagus (central confirmation is not required). Primary tumor or metastatic lesion must be HER2+ documented as HER2 gene amplification by FISH as positive (HER2:CEP17 ratio of ≥2.0) or IHC 3+.
• Metastatic or unresectable adenocarcinoma of stomach, GEJ, or esophagus that is evaluable or that is measurable for response as per RECIST 1.1 criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan.
• Adult subjects greater than 18 years of age
• Patients who received postoperative adjuvant therapy with a single-agent fluoropyrimidine and radiation are eligible.
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
• Adequate organ and bone marrow functions defined as follows:
• oAbsolute neutrophil count \>1,500 cells/ul
• Platelets \>100,000/ul
• Hemoglobin \>9.0g/dl
• INR \< or equal to 1.5 or INR \< or equal to 3 if patient is on warfarin
• Serum creatinine \< or equal to 1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CRCL) \> or equal to 60ml/min
• Serum electrolytes within the normal range (per institution standard) during screening.
• Total bilirubin less than or equal to 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< or equal to 3 times ULN
• Albumin \> or equal to 3g/dL

You may not qualify if:

• Prior treatment chemotherapy or HER2-directed therapy for metastatic gastric, GEJ or esophageal adenocarcinoma chemotherapy.
• Prior peri-operative therapy with a platinum-containing regimen.
• Angina secondary to fluoropyrimidine therapy in the adjuvant setting
• Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable/evaluable disease.
• Major surgery within 4 weeks prior to the first dose of KD019
• Left ventricular ejection fraction (EF) \<50% at baseline as measured by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Treatment with chronic immunosuppressants (e.g. cyclosporine following transplantation)
• Current known active infection with HIV, hepatitis B or C viruses
• Uncontrolled systemic disease
• Brain metastases that are:
• Untreated or
• Progressive or
• Have required any type of therapy (including radiation, surgery, steroids or anticonvulsant therapy) to control symptoms from brain metastases within 60 days prior to the first study treatment
• Leptomeningeal
• Hemorrhagic

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Neoplasms; Neoplasm Metastasis; Adenocarcinoma

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Jennifer Wu, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: July 31, 2014
• Study Start: December 1, 2014
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: August 1, 2014

Record last verified: 2014-07

Locations

US (1)