Trial Title:
Study of Bemcentinib Plus Pacritinib In Patients With Advanced Lung Adenocarcinoma
NCT ID:
NCT06516887
Condition:
Advanced Lung Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Adenocarcinoma of Lung
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Phase 1b of the study will be conducted to establish the maximum tolerable dose, after
pharmacokinetic samples from the first 10 subjects have been collected they will commence
Cycle 1, Day 1 treatment. Phase 2 will then be enrolled in a single arm comparison study
where some patients will be selected to undergo biopsy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
bemcentinib
Description:
Bemcentinib has been investigated in a phase I/II clinical trials for solid tumors. Phase
I and II clinical studies of BGB324 are ongoing in non-small cell carcinoma, in which
combinations with other agents such as Phase I study of docetaxel (NCT02922777),
erlotinib (NCT02424617), and pembrolizumab (NCT03184571) are also being investigated. In
a phase I dose escalation study of bemcentinib in combination with docetaxel study,
patients with treatment naïve, advanced lung adenocarcinoma receive docetaxel 75 mg/m2
given IV every 21 days in combination with bemcentinib. Bemcentinib dose will be
escalated in a standard 3+3 fashion until a maximum tolerated dose is determined.
Arm group label:
Pharmacokinetic Phase 1b (PK) Study Cohort
Arm group label:
Phase II Cohort
Intervention type:
Drug
Intervention name:
pacritinib
Description:
For use in clinical studies as an oral agent, pacritinib is supplied as size #0 hard
gelatin capsules with gray bodies and scarlet caps. Capsules contain 100 mg pacritinib
(free base) and the following inactive ingredients: microcrystalline cellulose NF,
polyethylene glycol 8000 NF, and magnesium stearate NF. The capsule gelatin is bovine
derived. Pharmacies at investigational sites will receive subject-specific bottles
containing 120 capsules packaged in 200 mL high-density polyethylene bottles with
child-resistant closures.
Arm group label:
Pharmacokinetic Phase 1b (PK) Study Cohort
Arm group label:
Phase II Cohort
Summary:
This is a Phase Ib/II, open-label, single institution dose-escalation, safety,
pharmacokinetics, pharmacodynamic and efficacy study.
Detailed description:
Specific Aim 1. Determine the safety, tolerability and maximum tolerated dose (MTD) of
pacritinib in combination with bemcentinib in patients with advanced lung adenocarcinoma.
We propose a prospective, open-label, phase Ib trial to evaluate safety, tolerability and
MTD of pacritinib (JAK2 inhibitor) in combination with bemcentinib (AXL inhibitor) in
patients with treatment refractory lung adenocarcinoma. The primary objectives of the
phase Ib study are to determine the maximum tolerated dose (MTD),
pharmacokinetics/pharmacodynamics (PK/PD), dose-limiting toxicities (DLTs) and efficacy
of oral pacritinib in combination with bemcentinib. This phase Ib part of the study will
use a Bayesian Optimal Interval (BOIN)70 design to determine MTD. This Bayesian
dose-finding approach combines the ease of implementation of the traditional "3+3" design
with the improved performance of more complex model-based designs in terms of accurately
identifying the MTD. Compared to the modified probability toxicity interval design, it
has a substantially lower risk of overdosing patients and generally has a higher
probability of correctly selecting the MTD. In the phase Ib part of the study, subjects
with advanced lung adenocarcinoma will be treated with pacritinib in combination with
bemcentinib at increasing doses until MTD for combination treatment has been established.
Six dose levels of combination treatments will be considered.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with histologically-or cytologically confirmed diagnosis of locally
advanced and/or metastatic lung adenocarcinoma (Stage IV/AJCC Edition 8) (any PD-L1
status) without actionable driver mutations, who has failed at least one line of
systemic treatment. Patients with locally advanced and/or metastatic lung
adenocarcinoma with driver mutation who have failed standard targeted therapies can
also be enrolled on this study.
2. Be refractory to, or intolerant of, an established therapy known to provide clinical
benefit for their condition. Patients can be eligible for study if they have failed
at least one line of treatment.
3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as
assessed by the investigator. Evaluable disease in phase 1 is allowed.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
(AppendixH)
5. Life expectancy of at least 3 months
6. Be ≥18 years of age
7. Negative pregnancy test (if female of childbearing potential)
8. Adequate liver function:
- Total bilirubin <1.5x upper limit of normal (ULN) (<3xULN for subjects
with liver metastases)
- Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT),
alkaline phosphatase <2.5 x ULN.
- If liver metastases are present, then AST and ALT <5 x ULN is allowed.
9. Adequate renal function with calculated creatinine clearance ≥30 mL/min by
Cockcroft-Gault Formula.
10. Adequate hematologic status:
- Absolute neutrophil count ≥1500 cells/mm3
- Platelet count ≥100,000 (plt/mm3)
- Hemoglobin ≥9 g/dL
11. Have no clinically significant abnormalities on urinalysis
12. Have acceptable coagulation status:
- Prothrombin time (PT) ≤ 1.5 x ULN
- Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
13. Be non-fertile or agree to use an adequate method of contraception. Sexually active
patients and their partners must use an highly effective method of contraception
(hormonal or barrier method of birth control; or abstinence) prior to study entry
and for the duration of study participation and for at least 90 days after the last
study drug dose. Female patients using hormonal contraceptive agent should use at
least one additional non-hormonal method of contraception (e.g., IUD, condom,
abstinence). Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
14. Have read and signed the IRB-approved informed consent form prior to any study
related procedure. If a patient is re-screened for the clinical trial or a protocol
amendment alters the care of an ongoing patient, a new informed consent form must be
signed.
15. Patients enrolled in the Expansion Cohort must be willing to consider pre-study and
on-study biopsies, if safe and medically feasible, as determined by a
board-certified interventional radiologist. Four to eight core samples will be
requested at each biopsy timepoint.
16. Patients must be able to swallow and tolerate oral medications.
Exclusion Criteria:
1. History of the following cardiac conditions:
1. An acute ischemic cardiac event (e.g., myocardial infarction) or
hospitalization for unstable angina within 3 months prior to first dose.
2. Abnormal left ventricular ejection fraction on echocardiography (less than the
lower limit of normal for a subject of that age at the treating institution or
Grade 2 severity according to the New York Heart Association as defined by
symptoms at less than ordinary levels of activity. Echo will only be considered
for symptomatic patients with heart disease and concerns for heart failure. The
Echo would be ordered by PI as standard of care.
3. Uncontrolled cardiac disease, including unstable angina, uncontrolled
hypertension (i.e., sustained systolic BP >160 mmHg or diastolic BP >90
mmHg), or need to change medication due to lack of disease control within 12
weeks prior to the provision of consent.
4. History or presence of bradycardia (≤55 bpm) or history of symptomatic
bradycardia, left bundle branch block, cardiac pacemaker or significant atrial
tachyarrhythmias as defined by the need for treatment.
5. Presence of any factors that increase the risk for QTc prolongation, e.g.,
resistant, or inadequately treated heart failure, presence of hypokalemia or
hypomagnesemia not corrected by, or not responding to, replacement therapy or
inadequately treated hypothyroidism as defined by the thyroid-stimulating
hormone not within the expected range of the institution.
6. Family history of long QTc syndrome or ventricular arrhythmias; personal
history of long QTc syndrome or previous drug induced QTc prolongation of at
least Grade 3 (QTc >500 ms). (Appendix I)
2. Have a corrected QT interval (QTcF, Fridericia's method) of >450 msec in men and
>470 msec in women.
3. Have a seizure disorder requiring anticonvulsants.
4. Presence of symptomatic central nervous system metastatic disease that requires
local therapy such as radiotherapy, surgery, or increasing dose of steroids within 2
weeks prior to Day 1 treatment.
5. Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior to
Day 1
6. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy.
7. Are pregnant or nursing.
8. Received treatment with radiation therapy, chemotherapy, or investigational therapy
within 28 days or 5 half-lives, whichever occurs first, prior to study entry.
9. Are unwilling or unable to comply with procedures required in this protocol.
10. Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis C.
Patients with history of chronic hepatitis that is not active are eligible.
11. Have a serious nonmalignant disease (e.g., hydronephrosis, liver failure (Child Pugh
class B or C), or other conditions) that could compromise protocol objectives in the
opinion of the clinical investigators.
12. Uncontrolled diarrhea (grade ≥ 2).
13. Recent bleeding (grade ≥2 within the past 3 months unless precipitated by another
event (e.g., trauma, surgery).
14. Use of anticoagulant or anti-platelet agents within the prior 14 days other than
baby aspirin.
15. Use of strong CYP3A4 inducers or inhibitors within 5 half-lives prior to cycle 1 day
1 treatment. Patients enrolled in PK study should not be taking a moderate/severe
CYP3A4 inhibitor or inducer.
16. Are currently receiving any other investigational agent.
17. Have exhibited allergic reactions to a similar structural compound or formulation as
pacritinib or bemcentinib.
18. Patients with severe lactose intolerance, hereditary galactose intolerance,
LAPP-lactase deficiency and/or glucose-galactose malabsorption at the discretion of
the PI>.
19. Have undergone significant surgery to the gastrointestinal tract that could impair
absorption or that could result in short bowel syndrome with diarrhea due to
malabsorption.
20. Have a history of severe adverse reaction (e.g., hypersensitivity reaction,
anaphylaxis) to sulfonamides.
21. Patients who are currently taking H2-receptor agonists (e.g., cimetidine,
ranitidine) or proton pump inhibitors (e.g., omeprazole) must be able to discontinue
their use at least seven days prior to the first dose of study treatment and
throughout the period they are receiving study treatment. Patients who are unable to
do so will be deemed ineligible.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Texas Health Science Center at San Antonio
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Contact:
Last name:
Epp Goodwin
Phone:
210-450-5798
Email:
goodwin@uthscsa.edu
Investigator:
Last name:
John Sarantopoulos, MD
Email:
Principal Investigator
Investigator:
Last name:
Josephine Taverna, MD
Email:
Sub-Investigator
Start date:
September 1, 2024
Completion date:
September 1, 2027
Lead sponsor:
Agency:
The University of Texas Health Science Center at San Antonio
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
The University of Texas Health Science Center at San Antonio
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06516887
