A Study to Evaluate the Safety and Tolerability of ETC-1922159 in Advanced Solid Tumours



Status:Recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:1/11/2018
Start Date:October 2015
End Date:August 2018
Contact:Veronica Diermayr, PhD
Email:vdiermayr@d3.a-star.edu.sg
Phone:6598171664

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A Phase 1A/B Study to Evaluate the Safety and Tolerability of ETC-1922159 in Advanced Solid Tumours

This is a Phase 1A/B study consisting of three parts. Part A is a non-randomised, open-label,
sequential evaluation of the safety, pharmacokinetics, maximum tolerated dose (MTD), and
recommended dose (RD) of ETC-1922159 in patients with advanced or metastatic, or unresectable
solid malignancies, for whom no approved treatment option or standard of care is available.
Dose escalation, with the goal of identifying the MTD and RD, will be guided by an ordinal
continual reassessment method (oCRM) model with a cohort size of one patient.

Part A extension is a non-randomised, non-comparative, open-label evaluation of the safety
and tolerability of ETC-1922159 together with the bone protective treatment (denosumab) in
patients with advanced or metastatic, or unresectable solid malignancies, for whom no
approved treatment option or standard of care is available.

Part B will be a non-randomised, non-comparative, open-label evaluation of the safety and
tolerability of the RD of ETC 1922159 in patients with advanced or metastatic, or
unresectable solid malignancies, for whom no approved treatment option or standard of care is
available, with a molecular phenotype that is expected to make them sensitive to PORCN
inhibitor treatment.

It is anticipated that the study will take approximately 42 months to complete (approximately
30 months for Part A and Part A extension, and approximately 12 months for Part B).


Inclusion Criteria:

- 18+ yrs (US), 21+ yrs (Singapore)

- Histologically/cytologically confirmed advanced/metastatic or unresectable solid
tumors, no treatment options

- Radiologically confirmed disease progression

- Evaluable/measurable disease by RECIST

- ECOG 0-2

- Life expectancy ≥3 mos

- Organ function:

- Absolute neutrophil count ≥1.0×109/L

- Platelets ≥100×109/L (w/o transfusions w/in 21 days)

- Hemoglobin ≥9 g/dL

- PT and PTT w/in ≤1.5× ULN

- INR ≤1.5× ULN

- Total bilirubin ≤1.5× ULN

- AST and/or ALT ≤2.5× ULN, <5× ULN w/liver metastases

- Creatinine clearance ≥60 mL/min

- Total Ca (corrected for serum albumin) w/in normal limits

- Mg ≥ lower limit of normal

- Normal urinalysis

- Pts w/ osteopenia (T-score of -1 to -2.5 at L/R total hip, L/R femoral neck or lumbar
spine [L1-L4]) eligible

- Neg pregnancy test

Part A extension only:

• Has a primary tumor or a metastatic site that is accessible for pre- and post-dose biopsy
without subjecting patient to high level of risk

Part B only:

- Tumor tissue available if biopsy consent not provided, if no archival tumor tissue
available and pt provides consent, pre-dose biopsy will be done

- Tumor tissue receptive to Wnt signalling in biopsy

Exclusion Criteria:

- Male w/partner(s) (childbearing) unwilling to use contraception

- Female of childbearing potential, unless birth control used on study and 12 wks
post-treatment.

- Pregnant/nursing female

- Current or anti-cancer therapy w/in 4 wks pre-study or w/Grade ≤1 side effects not
resolved w/in 4 wks pre-study

- Other IPs w/in 4 wks or 5 half-lives (whichever is longer) prior to study drug

- Malignancy not in remission or w/in last 3 yrs (exceptions: basal or skin squamous
cell carcinoma or in situ cervix cancer)

- CNS metastases, unless treated w/ surgery, whole brain radiation or stereotactic
radiosurgery, and stable disease ≥8 wks w/o steroid use for ≥4 wks prior to study drug

- Radiation w/in 4 wks, or limited field radiation w/in 2 wks, prior to study drug, or
w/unresolved Grade ≤1 side effects

- Radiation to spine/pelvis bone or chemoradiation to pelvic organs

- Surgical procedure w/in 4 wks of starting study drug. Or pt has surgery-related
complications to Grade ≤1

- Interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or
pulmonary hypersensitivity pneumonitis

- Bisphosphonate therapy (osteoporosis or symptomatic hypercalcaemia) or denosumab
(osteoporosis) prior to study drug

- Osteoporosis (T-score of <−2.5 at L/R total hip, L/R femoral neck, or lumbar spine
[L1-L4] by DEXA scan)

- Symptomatic vertebral fragility fractures or fragility fracture of hip, pelvis, wrist,
or other location (fragility fracture - any fracture w/out trauma or as a result of a
fall from ≤standing height)

- Moderate (25%-40% decrease vertebral ht.) or severe (>40% decrease vertebral ht.)
morphometric vertebral fractures

- β-CTX serum level >1000 pg/mL (morning after ≥10hrs fasting)

- Thyrotropin/25-hydroxyvitamin D levels < lower limit of normal

- Bone metastases

- Long QT or prolonged QTc (>460 ms)

- Thiazolidinedione peroxisome proliferator-activated receptor gamma agonist (e.g.
Actos® [pioglitazone] and Avandia® [rosiglitazone]) w/in 4 wks prior to study drug

- PO or IV glucocorticoid for ≥4 wks at daily dose eq. to ≥7.5 mg of PO prednisone w/in
12 wks prior to study drug dosing

- Hyperparathyroidism, Paget's disease or osteomalacia

- Bleeding disorder/coagulopathy

- Heparin, warfarin or similar anti-coagulants (except. low molecular weight heparin for
treatment/prophylaxis) currently or w/in 4 wks of study drug

- Heart failure, ischemic heart disease, uncontrolled hypertension, uncontrolled
diabetes mellitus, psychiatric condition, ongoing cardiac arrhythmia requiring
medication (Grade ≥2, by NCI CTCAE v. 4.03), or significant/unstable concurrent
medical illness by investigator opinion

- HIV or active bacterial, viral or fungal infections

- Gastric bypass

Part A extension and B only:

• Cannot start treatment with the bone protective treatment with denosumab SC

Part B only:

• APC, CTNNB1, WTX [FAM123], AXIN1 and GSK3B in tumor
We found this trial at
3
sites
Houston, Texas 77030
Principal Investigator: Vivek Subbiah, MD
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from
Houston, TX
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Aurora, Colorado 80045
Principal Investigator: Wells A. Messersmith, MD, F.A.C.P.
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mi
from
Aurora, CO
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Singapore,
Principal Investigator: David Tan Shao Peng
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mi
from
Singapore,
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