Overview

This trial is active, not recruiting.

Conditions malignant solid tumor, metastatic epha2 positive cancer
Treatments 89zr-ds-8895a, ds-8895a
Phase phase 1
Sponsor Ludwig Institute for Cancer Research
Collaborator Daiichi Sankyo Co., Ltd.
Start date September 2014
End date December 2016
Trial size 9 participants
Trial identifier NCT02252211, LUD2014-002

Summary

The purpose of this study is to find a more effective way of treating solid tumors. This study will test the safety, bio-distribution, and tumor uptake of a new treatment for cancer called DS-8895a in patients with advanced solid tumors.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
89zr-ds-8895a
Cohort Number: 1; No. Pts: 3-6; Day 1 89Zr-DS8895a dose: 0.2 mg/kg Cohort Number 2; No. Pts.: 3-6; Day 1 89Zr-DS8895a dose: 0.2 mg/kg Cohort Number 3; No. Pts.: 3-6; Day 1 89Zr-DS8895a dose: 0.2 mg/kg Cohort Number 4; No. Pts.: 3-6; Day 1 89Zr-DS8895a dose: 0.2 mg/kg
ds-8895a
Cohort Number: 1; No. Pts: 3-6; DS-8895a dose rest of cycle: 1 mg/kg Cohort Number 2; No. Pts.: 3-6; DS-8895a dose rest of cycle: 3 mg/kg Cohort Number 3; No. Pts.: 3-6; DS-8895a dose rest of cycle: 10mg/kg Cohort Number 4; No. Pts.: 3-6; DS-8895a dose rest of cycle: 20 mg/kg Patients will receive an initial 89Zr trace labelled infusion of DS-8895a. DS-8895a will then be infused on Day 8, and second weekly infusions of DS-8895a, for a further two infusions, will subsequently occur. The day 36 infusion of DS-8895a will also be trace labelled with 89Zr, with subsequent PET imaging and pharmacokinetic sampling. Four dose levels (1, 3, 10 and 20mg/kg) will be evaluated, with 3-6 patients entered at each dose level.

Primary Outcomes

Measure
To determine the safety of DS-8895a in patients with advanced or metastatic EphA2 positive cancers
time frame: 28 Days

Secondary Outcomes

Measure
To determine the biodistribution and tumor uptake of 89Zr- DS-8895a.
time frame: 60 days
To describe anti-tumor response.
time frame: 60 days
To determine the pharmacokinetics of 89Zr- DS-8895a.
time frame: 60 Days
Pharmacodynamic response following DS-8895a infusion in patients with advanced or metastatic EphA2 positive cancers.
time frame: 60 Days

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Advanced or metastatic EphA2 positive cancer (based on IHC of archived or fresh tumor tissue) 2. Patients must have malignant tumor which is refractory to standard treatment 3. At least one reference tumor > 1cm in size for assessment of tumor uptake of 89Zr-DS-8895a. 4. Expected survival of at least 3 months. 5. ECOG Performance Status ≤ 1 6. Within the last 1 week prior to first study drug administration, laboratory parameters for vital functions should be in the normal range. Out of range values that are not clinically significant will be permitted, except for the following laboratory parameters, which must be within the ranges specified: Lab Parameter Range 1. Neutrophils 1.5 x 109/L 2. Platelets 90 x 109/L 3. INR ≤ 1.5 4. Serum AST and ALT ≤2.5 x ULN; (≤5 x ULN if liver metastases) 5. Serum bilirubin ≤ 1.5 x ULN 7. Calculated creatinine clearance ≥55mL/min 8. Age ≥ 18 years 9. Able and willing to give valid written informed consent Exclusion Criteria: 1. Active central nervous system metastases. Definitively treated metastases are allowed if stable for 6 weeks off therapy. 2. Known immunodeficiency or HIV positivity. 3. Serious illnesses e.g. serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would interfere with the ability of the patient to fulfill the study requirements. 4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to first study drug administration, that in the opinion of the investigator has >10% risk of relapse within 12 months 5. Significant allergic reaction to prior antibody infusions. 6. Chemotherapy, radiotherapy or investigational agent within 4 weeks prior to first study drug administration. 7. Regular corticosteroid, NSAID (other than paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to first drug administration (intermittent dosing permitted if less than 4 doses within a 3 day period). 8. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. 9. Lack of availability for clinical follow-up assessments. 10. Pregnancy or breastfeeding. 11. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Additional Information

Official title A Phase I Safety and Bioimaging Trial of DS-8895a in Patients With Advanced or Metastatic EphA2 Positive Cancers
Principal investigator Andrew Scott, MD
Description This is a dose escalation, non-randomized, open label, single site study of DS-8895a in patients with advanced or metastatic EphA2 positive cancers. Patients will receive an initial 89Zr trace labelled infusion of DS-8895a, followed by safety assessments, PET imaging and pharmacokinetic sampling over a one week period. DS-8895a will then be infused on Day 8, and second weekly infusions of DS-8895a, for a further two infusions, will subsequently occur. The day 36 infusion of DS-8895a will also be trace labelled with 89Zr, with subsequent PET imaging and pharmacokinetic sampling. Four dose levels (1, 3, 10 and 20mg/kg) will be evaluated, with 3-6 patients entered at each dose level. Those patients who respond or have stable disease on RECIST at Day 50 restaging may continue on biweekly treatment of DS-8895a until disease progression, with restaging CT scans every 6 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Ludwig Institute for Cancer Research.