Brief Title
A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma
Official Title
Phase II Trial of LP-300 in Combination With Carboplatin and Pemetrexed in Never Smoker Patients With Relapsed Advanced Primary Adenocarcinoma of the Lung After Treatment With Tyrosine Kinase Inhibitors (The HARMONIC Study)
Brief Summary
This study is being conducted to determine clinical advantages for LP-300 in combination with
carboplatin and pemetrexed in the never smoker patient population. The primary objectives of
this study are to determine progression-free survival (PFS) and overall survival (OS) in the
study-defined patient population when LP-300 is co-administered with the standard of care
chemotherapy drugs carboplatin and pemetrexed compared to carboplatin and pemetrexed alone.
This has been designed as a multicenter, open label, phase II trial with 90 patients to be
enrolled in the United States.
Detailed Description
Patients who are never smokers with lung adenocarcinoma and have relapsed after treatment
with tyrosine kinase inhibitors (TKIs) will be eligible for enrollment. The trial will
proceed in two stages. In the safety lead-in stage, 6 patients will be enrolled and treated
with the LP-300 co-administered in combination with carboplatin and pemetrexed. In the
absence of any safety signals in these patients, the second stage of the trial protocol will
begin. This second stage consists of randomizing patients in a 2:1 allocation ratio to one of
two arms: investigational arm of carboplatin, pemetrexed, and LP-300 or the standard of care
arm of carboplatin and pemetrexed. Treatment of both groups will be on Day 1 of a 21-day
cycle. A total of 6 treatment cycles are planned, with the possibility of patients going into
a pemetrexed maintenance phase afterwards.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-free survival (PFS)
Secondary Outcome
Objective response rate (ORR)
Condition
Adenocarcinoma of Lung
Intervention
LP-300
Study Arms / Comparison Groups
LP-300 in Combination with Pemetrexed and Carboplatin
Description: LP-300 (investigational drug) + Pemetrexed and Carboplatin (standard of care chemotherapies) Dosing occurs on Day 1 of a 21-day cycle.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
90
Start Date
August 12, 2022
Completion Date
May 2025
Primary Completion Date
November 2024
Eligibility Criteria
Inclusion Criteria:
1. Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III
or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung
with specific actionable genomic alterations (e.g., mesenchymal epithelial transition
(MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK), epidermal growth
factor receptor (EGFR), neurotrophic tyrosine receptor kinase (NTRK) fusions, etc.).
If pathological or radiological findings are inconclusive for a diagnosis of primary
adenocarcinoma of the lung, additional studies must be performed to confirm primary
lung versus metastatic adenocarcinoma. Patients with no known actionable genomic
alterations are ineligible to enroll in the study.
2. Locally advanced inoperable or metastatic lung cancer.
3. Patients must be never smokers, as defined by the United States Center for Disease
Control: a never smoker is an adult who has never smoked, or who has smoked less than
100 cigarettes (or equivalent in other tobacco product) in his or her lifetime.
4. Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs)
for non-small cell lung cancer but have experienced disease progression, unacceptable
TKI-related toxicities, or are unable to tolerate the further use of TKIs.
5. Prior radiation therapy is allowed, provided (1) that at least one area of measurable
tumor (by computed tomography (CT) scan with at least one target lesion) per Response
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been subject to
prior irradiation, and (2) that any such therapy is completed and any
radiation-induced sequelae are recovered at least 21 days before randomization.
6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1.
7. Patients who are at least 18 years of age.
8. Patients with documented stable central nervous system (CNS) metastases with no
cognitive deficits, or progressive sensory or motor deficits, or seizures during the
last 21 days prior to enrollment are eligible. Patients must have discontinued
anti-seizure medications and steroids at least 14 days prior to patient enrollment.
9. Patients must have fully recovered from any prior major surgical or diagnostic staging
procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at
least 30 days before enrollment.
10. Patients must have adequate bone marrow, adequate hepatic function, and baseline
creatinine levels documented by specific laboratory criteria within 21 days prior to
enrollment, including the following:
- White blood cell count ≥ 2 x 10*9/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
- Hemoglobin ≥ 10 g/dL
- Platelet count ≥ 100 x 10*9/L
- Total bilirubin < 1.5 x the upper limit of normal (ULN). For patients with
Gilbert's syndrome, total bilirubin < 2.5 x ULN
- Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤
2.5 x ULN
- Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x
ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L.
- Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gault
methodology (Cockcroft 1976)
- Magnesium ≥ 1.7 mg/dL
11. Female patients of child-bearing potential must have a negative pregnancy test and
must agree to use an acceptable contraceptive method during the study and for 12 weeks
after their last dose of study treatment. Male patients with partners of child-bearing
potential must also agree to use an adequate method of contraception for the duration
of the study and for 12 weeks after their last dose of study treatment.
Note: Medically acceptable contraceptives include: (1) surgical sterilization (such as
a tubal ligation, hysterectomy, or vasectomy), (2) approved hormonal contraceptives
(such as birth control pills, patches, implants or injections), (3) barrier methods
(such as a condom or diaphragm) used with a spermicide, (4) an intrauterine device
(IUD), or (5) avoiding sexual activity that could cause you or your partner to become
pregnant. Contraceptive measures and other medications sold for emergency use after
unprotected sex, are not acceptable methods for routine use. If a female patient
becomes pregnant, study therapy must be discontinued immediately.
12. Patients must have been disease-free at least two years for other malignancies,
excluding:
- Curatively-treated basal cell carcinoma,
- Ductal carcinoma in situ (DCIS) of the breast
- Non-melanomatous carcinoma of the skin, or
- Carcinoma in situ of the cervix.
13. Be willing to provide an archival tumor tissue sample, if available. The archival
sample must be from a tumor lesion that was not previously irradiated. Formalin-fixed,
paraffin embedded (FFPE) tissue blocks are preferred to slides. The sample must have
been obtained less than 36 months prior to consent.
14. Provide signed, written, Institutional Review Board (IRB) approved informed consent
prior to any screening procedures.
Exclusion Criteria:
1. Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma,
or any form of mixed (e.g., small cell and adenocarcinoma or squamous and
adenocarcinoma) histopathological diagnosis of primary lung cancer.
2. Patients with metastatic adenocarcinoma arising from any primary site other than the
lung.
3. Patients who have received any prior investigational agents except for investigational
TKI drugs. The investigational TKI drug washout period is ≥ 5 half-lives or 2 weeks,
whichever is shorter.
4. Patients who have received any form of prior systemic chemotherapies or hormonal
therapies for non-small cell lung cancer (excluding dexamethasone or corticosteroids)
or who have received any prior immunotherapies.
5. Patients taking medications that are sensitive substrates of CYP2C19 or P-gp
transporters
6. Patients with recent onset (within 6 months of randomization) of congestive heart
failure (New York Heart Association Classification Class II or greater), angina
pectoris, unstable angina pectoris, serious uncontrolled cardiac arrhythmias,
myocardial infarction, stroke, or transient ischemic attacks.
7. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of > 470
msec
8. Patients with unstable CNS metastases (characterized by progressive sensory/motor
impairment, cognitive/speech impairment, or seizure activity) within 21 days before
enrollment.
9. Patients who do not have at least one (1) measurable disease site that has not been
previously irradiated.
10. Patients who are known to be positive for human immunodeficiency virus (HIV),
hepatitis B virus surface antigen (HbsAg) or hepatitis C virus (HCV).
11. Patients with active infections, active interstitial lung disease, uncontrolled high
blood pressure, uncontrolled diabetes mellitus, uncontrolled seizures (not due to CNS
metastases) within the last 6 months, or other serious underlying medical condition.
12. Patients with documented hypersensitivity to any of the study medications or
supportive agents that may be used.
13. Patients who are pregnant or are breastfeeding.
14. Patients who have undergone blood transfusions within 10 days before randomization.
15. Any other medical intervention or other condition which, in the opinion of the
Principal Investigator, could compromise adherence to study requirements or confound
the interpretation of study results.
16. Patients who have a life expectancy of less than 3 months.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 972-277-1136, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05456256
Organization ID
LTRN300-2LC01-OR21
Responsible Party
Sponsor
Study Sponsor
Lantern Pharma Inc.
Study Sponsor
, ,
Verification Date
February 2023