Bemcentinib + Pacritinib for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: The University of Texas Health Science Center at San Antonio
Must not be taking: Anticonvulsants, Anticoagulants, CYP3A4 drugs, others
Disqualifiers: Cardiac conditions, CNS metastases, Infections, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a Phase Ib/II, open-label, single institution dose-escalation, safety, pharmacokinetics, pharmacodynamic and efficacy study.
Will I have to stop taking my current medications?
The trial requires that you stop taking H2-receptor agonists (like cimetidine or ranitidine) and proton pump inhibitors (like omeprazole) at least seven days before starting the study treatment and throughout the study. If you are taking strong CYP3A4 inducers or inhibitors, you must stop them at least 5 half-lives before starting the treatment.
How is the drug combination of Bemcentinib and Pacritinib unique for lung cancer treatment?
The combination of Bemcentinib and Pacritinib for lung cancer is unique because it involves two drugs that target specific pathways in cancer cells, potentially offering a novel approach compared to traditional chemotherapy regimens. Bemcentinib is known to inhibit AXL, a protein that helps cancer cells survive and spread, while Pacritinib targets JAK2, a protein involved in cell growth, which may provide a different mechanism of action compared to existing treatments.
12345Eligibility Criteria
Adults with advanced lung adenocarcinoma who've failed at least one systemic treatment can join. They must have measurable disease, good organ function, no serious heart conditions or infections, and be able to swallow pills. Women of childbearing potential need a negative pregnancy test and agree to use contraception.Inclusion Criteria
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator
Have no clinically significant abnormalities on urinalysis
Have acceptable coagulation status: Prothrombin time (PT) ≤ 1.5 x ULN, Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
+14 more
Exclusion Criteria
History of the following cardiac conditions: An acute ischemic cardiac event (e.g., myocardial infarction) or hospitalization for unstable angina within 3 months prior to first dose, Abnormal left ventricular ejection fraction on echocardiography, Uncontrolled cardiac disease, History or presence of bradycardia, Presence of any factors that increase the risk for QTc prolongation, Family history of long QTc syndrome or ventricular arrhythmias, Personal history of long QTc syndrome or previous drug induced QTc prolongation
I do not have any serious infections that need treatment with medication.
I can stop taking my acid reflux medication 7 days before starting the study treatment.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase Ib Treatment
Participants receive bemcentinib and pacritinib in combination to determine the maximum tolerated dose (MTD) using a Bayesian Optimal Interval (BOIN) design
4 weeks
Multiple visits for PK sampling on Days 1, 2, 7, 8, 14, and 22
Phase II Treatment
Participants receive the maximum tolerated dose of bemcentinib and pacritinib, with up to 15 participants undergoing a biopsy
Up to 48 months
Follow-up
Participants are monitored for progression-free survival and overall survival
Up to 48 months
Participant Groups
The trial is testing the combination of two drugs, Bemcentinib and Pacritinib, for treating advanced lung adenocarcinoma. It's an early-phase study assessing dosage safety, how the body processes the drugs (pharmacokinetics), their effects on cancer (pharmacodynamics), and effectiveness.
2Treatment groups
Experimental Treatment
Group I: Phase II CohortExperimental Treatment2 Interventions
Of these participants taking the Maximum tolerated dose, up to 15 will undergo a biopsy. Progression free survival will be the primary objective of this study phase.
Group II: Pharmacokinetic Phase 1b (PK) Study CohortExperimental Treatment2 Interventions
Patients will receive bemcentinib and pacritinib in combination from Days 1 to Day 28. PK samples will be collected on Day 1 (pre-dose, 4, 6h), pre-dose Day 2, Day 7 (pre-dose, 4h and 6h post-dose), pre-dose Day 8, pre-dose Day 14, and Day 22 (pre-dose and 6h post-dose) samples. The Day 22 sample will cover the steady state values for both compounds.
Six dose levels of combination treatments will be considered:
* Dose level -1: pacritinib 100 mg oral dose (p.o.) daily + bemcentinib 50 mg p.o. daily;
* Dose level 1: pacritinib 100 mg oral dose (p.o.) twice daily (BID) + bemcentinib 50 mg p.o. daily;
* Dose level 2: pacritinib 100 mg p.o. BID + bemcentinib 75 mg p.o. daily;
* Dose level 3: pacritinib 100 mg BID + bemcentinib 100 mg p.o. daily;
* Dose level 4: pacritinib 200 mg BID + bemcentinib 100 mg p.o. daily;
* Dose level 5: pacritinib 200 mg BID + bemcentinib 125 mg p.o. daily.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Texas Health Science Center at San AntonioSan Antonio, TX
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Who Is Running the Clinical Trial?
The University of Texas Health Science Center at San AntonioLead Sponsor
National Cancer Institute (NCI)Collaborator
References
[Efficacy of chemotherapy with carboplatin-paclitaxel plus bevacizumab for previously treated patients with advanced non-small cell carcinoma]. [2015]There have been few reports on the efficacy or safety of combination therapy with carboplatin-paclitaxel plus bevacizumab(TC+Bev)in previously treated patients with non-small cell lung carcinoma(NSCLC).
PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. [2022]PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment. [2021]Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens.
PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting. [2023]Regimens with bevacizumab (Bev) have high response rates. We previously showed the efficacy of Bev plus carboplatin (CBDCA)/nab-paclitaxel (nab-PTX) in the treatment of non-squamous (non-SQ) non-small lung cell cancer (NSCLC) with malignant pleural effusion in a phase II trial. However, few studies have reported the efficacy and safety of this regimen. Therefore, we conducted a retrospective analysis of the efficacy and safety of Bev plus CBDCA/nab-PTX for patients with NSCLC.