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Clinical Trial VICCGI13114

Title

A Two Part, Phase 1, Multi-center, Open-label Study of DKN-01 in Combination with Weekly Paclitaxel; Arm A: A Dose-Escalation Study in Patients with Relapsed or Refractory Esophageal Cancer or Gastro-esophageal Junction Tumors; Arm B: An Expansion Cohort in Patients with Relapsed or Refractory Esophageal Cancer or Gastro-esophageal Junction Tumors

Principal Investigator(s)

Emily Chan

Details

  • Protocol No. VICCGI13114
  • Open Date: 08/04/2014
  • Staging: Phase I
  • Age Group: Adults
  • Scope: National
  • Objective: To characterize the safety and tolerability of DKN-01 in combination with weekly paclitaxel in patients with refractory/recurrent esophageal or gastro-esophageal junction cancer
  • Disease Sites: Phase I; Esophageal; Gastric/Gastroesophageal
  • Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: DKN-01; Paclitaxel
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT02013154
  • Secondary Protocol No: DEK-Dkk1-P102

Description

This study is being done to see how safe an investigational drug combined with the standard of care is and how well it will work to help people with refractory/recurrent esophageal or gastro-esophageal junction cancer. Patients aking part in this study may help to answer the following research question(s): how much DKN-01 should be given together with paclitaxel to patients; how DKN-01 and paclitaxel work together;

Eligibility

Ages Eligible for Study:30 Years and older
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No

Criteria

Inclusion Criteria:
• In advanced esophageal malignancies:
• Participants with histologically confirmed recurrent or metastatic esophageal or gastro-esophageal junction squamous cell or adenocarcinoma whose tumors express Dkk-1 by immunohistochemistry (IHC)
• Participants must be refractory or intolerant to at least one prior standard therapy(ies) for metastatic or locally advanced disease
1. If prior therapy consisted of palliative chemoradiation therapy it will be considered one line of therapy
2. Prior treatment with paclitaxel as part of a definitive therapy regimen is acceptable provided the patient is not intolerant of paclitaxel
• Must have one or more tumors measurable on radiographic imaging as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
• Must be ambulatory
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. A performance status of 2 on the ECOG scale may be entered upon the review and approval of the medical monitor
• Have an estimated life expectancy of at least 3 months, in the judgment of the investigator
• Disease-free of active second/secondary or prior malignancies for equal to or over 2 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
• Acceptable liver function of:
1. Bilirubin less than or equal to (≤) 1.5 times upper limit of normal (ULN)
2. Aspartate aminotransferase (AST)(SGOT), alanine aminotransferase (ALT)(SGPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
• Acceptable renal function:
a. Creatinine normal for age; if serum creatinine is abnormal for age the patient must have a calculated creatinine clearance greater than or equal to (≥) 50 mL/min using the Cockcroft and Gault Method.
• Acceptable hematologic status of:
1. Granulocyte ≥ 1500 cells/mm3
2. Hemoglobin ≥ 9 g/dL (transfusion permitted within 30 days of study entry)
3. Platelet count ≥ 100,000 (plt/mm3)
• Acceptable coagulation status:
1. Prothrombin time/partial thromboplastin time (PT/PTT) ≤ 1.2 x ULN (unless receiving anticoagulation therapy, if receiving anticoagulation therapy, eligibility will be based upon the international normalised ratio(INR) as follows):
2. INR ≤ 1.6 (unless receiving anticoagulation therapy). If receiving anticoagulant: INR ≤ 3.0 and no active bleeding, (i.e., no bleeding within 14 days prior to first dose of study therapy)
• For men and women of child-producing potential, the use of effective contraceptive methods during the study and for 6 months following the last dose of study drug Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) during the study, and must agree to use adequate contraception prior to study entry and for 6 months after their last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Exclusion Criteria:
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6months, unstable arrhythmia
• Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study
• Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy
• Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
• History of major organ transplant (for example: heart, lungs, liver and kidney)
• History of autologous or allogenic bone marrow transplant
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Pregnant or nursing women
• History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant. Degenerative changes of the hip joint are not exclusionary. Screening of asymptomatic participants is not required.
• Symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Radiation must have been completed at least 14 days prior to study entry. Screening of asymptomatic participants without a history of CNS metastases is not required
• Clinically significant peripheral neuropathy at the time of study entry
• Known osteoblastic bony metastasis. Screening of asymptomatic participants without a history of metastatic bony lesions is not required
• Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days for nitrosoureas or mitomycin C)
• Treatment with low dose chemotherapy concurrent with radiation within 14 days prior to study entry
• Treatment with radiation therapy within 14 days prior to study entry
• Participants who are currently receiving any other investigational agent or have received an investigational agent within last 30 days of study entry or 5 half-lives, whichever is longer
• Previously treated with an anti-Dkk-1 therapy
• Participants who have a history of hypersensitivity reactions to TAXOL® or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil)
• Significant allergy to a pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the participant