A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of A-337 in Patients with Advanced Solid Tumors

Phase 1

• Conditions: Cancer; Cancer - Lung - Non small cell; Cancer - Other cancer types

• Registration Number: ACTRN12617001181392
• Lead Sponsor: INC Research Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-11
• Study Completion: 2019-05-31
• Last Update Posted: 23 March 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. Histologically or cytologically confirmed advanced malignant solid tumor
that is refractory to, intolerant of, or for which no standard of therapy is available.
2. Advanced solid tumors that are known to widely express EpCAM, including
but not limited to colorectal cancer, gastric cancer, lung cancer, ovarian cancer and
prostate cancer.
3. At least one measurable tumor lesion as per RECIST criteria v1.1 defined as
having at least one dimension with a minimum size of 10 mm in the longest
diameter by CT or MRI scan for non-nodal lesions or > or equal to 15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 28
days prior to the first dose.
4. Adequate archival tumor tissue available or willingness to have a fresh
biopsy. A fresh pre-treatment biopsy is compulsory for the first six patients
enrolled at the expansion stage.
5. Age > or equal to 18 years
6. ECOG performance status < or equal to 2
7. Life expectancy of at least 3 months
8. Ability to understand the patient information and informed consent form.
9. Signed and dated written informed consent

Exclusion Criteria

1. Inadequate hematologic function, defined by: Neutrophil count < 1,500/mm3
(= 1.5 x 10^9/L), Platelet count < 100,000/mm3 (= 100 x 10^9/L), White blood
cells (WBC) < 1,500/mm3 (3 x10^9/L), Hemoglobin < 9.0 g/dL at Screening.
2. Abnormal renal or hepatic function as defined by:
• ALT and AST > 2 x ULN, in case of liver metastases 3 x ULN
• Total bilirubin > 1.5 x ULN
• Creatinine clearance < 50 ml/min calculated by the Cockroft-Gault formula
or modification of diet in renal disease (MDRD)
• Coagulation: International Normalized Ratio (INR) < or equal to 1.6 (unless receiving
anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a
stable dose (minimum duration 14 days). If receiving warfarin, the subject must
have an INR < or equal to 3.0 and no active bleeding (ie, no bleeding within 14 days prior to
first dose of study drug). Subjects on low molecular weight heparin will be allowed.
3. Decompensated liver cirrhosis.
4. Subject with known central nervous system (CNS) metastases, unless
metastases are treated and stable for at least 4 weeks and the subject has not been
taking systemic steroids < or equal to 10mg prednisone/day or equivalent. Patients with
leptomeningeal disease or cord compression are excluded.
5. Any concurrent disease, medical or social condition that could affect
compliance with the protocol or interpretation of results as judged by the
investigator. In particular, patients with the following conditions are not allowed to
enter the study:
• Active infection or known bacteremia
• Known infection with human immunodeficiency virus (HIV) or chronic
infection with hepatitis B virus or hepatitis C virus
• Severe dyspnea or pulmonary dysfunction or need for continuous supportive
oxygen inhalation
• Insufficient cardiac function defined as NYHA (New York Heart Association)
Grade 3 or 4.
• History of myocardial infarction or unstable angina within 6 months prior to
Day 1.
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Clinically significant cardiac arrhythmias, uncontrolled hypertension
SBP>180 mmHg and DBP>100 mmHg
• History of autoimmune disease including, not limited to celiac
disease, diabetes mellitus type 1, inflammatory bowel disease, multiple sclerosis,
psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
6. Treatment with immune modulators including, but not limited to,
cyclosporine and tacrolimus within 2 weeks prior to enrollment; systemic steroids
< or equal to 10 mg prednisone or equivalent per day are allowed as well as ophthalmic,
inhaled or nasal steroids..
7. Pregnant, nursing women or women of childbearing potential who are not
willing to use effective forms of contraception during participation in the study and
at least three months thereafter. Positive pregnancy test (HCG) within 3 days prior
to Day 1.
8. Male patients with partners of child-bearing potential who are not willing to
use effective contraception during the trial and for at least three months thereafter,
unless surgically sterile.
9. Any anti-cancer therapy, including chemotherapy, hormonal therapy,
biologic therapy, or radiotherapy within 4 weeks prior to initiation of study
treatment with the following exceptions:
• Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists
for prostate cancer
• Hormone-replacement therapy or oral contraceptives
• Palliative radiation to bone metastases > 2 weeks prior to

Study & Design

• Study Type: Interventional
• Study Design: Not specified