LP-300 + Chemotherapy for Lung Adenocarcinoma EGFR
(HARMONIC Trial)
Recruiting in Palo Alto (17 mi)
+25 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Lantern Pharma Inc.
Must not be taking: CYP2C19, P-gp substrates
Disqualifiers: Small cell, Squamous cell, Cardiac issues, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests a new drug, LP-300, combined with two existing chemotherapy drugs in never smokers with a specific type of lung cancer who did not respond to previous treatments. The goal is to see if this combination improves survival by making the chemotherapy more effective.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop all current medications, but it does mention a 'washout period' for tyrosine kinase inhibitors (TKIs) of at least 5 half-lives or 2 weeks, whichever is shorter. Also, you cannot take medications that are sensitive substrates of CYP2C19 or P-gp transporters.
What data supports the effectiveness of the drug combination LP-300, Carboplatin, and Pemetrexed for lung adenocarcinoma?
Research shows that Pemetrexed, when combined with Carboplatin, has demonstrated antitumor activity and mild toxicity in treating non-small cell lung cancer, which is a type of lung cancer similar to lung adenocarcinoma.
12345Is the combination of LP-300 and chemotherapy safe for humans?
Pemetrexed, a drug used in combination with carboplatin for lung cancer, has been shown to have mild side effects when patients take folic acid and vitamin B12 supplements. Common side effects include fatigue, nausea, and vomiting, but these are generally manageable.
36789What makes the LP-300 + Chemotherapy drug unique for lung adenocarcinoma?
The LP-300 + Chemotherapy treatment is unique because it combines LP-300, a novel agent, with carboplatin and pemetrexed, which are standard chemotherapy drugs. LP-300 is designed to enhance the effectiveness of chemotherapy by potentially reducing toxicity and improving outcomes, offering a new approach compared to traditional chemotherapy regimens.
810111213Eligibility Criteria
This trial is for never smokers over 18 with advanced lung adenocarcinoma, including those who've had TKI treatment but now show disease progression or can't tolerate TKIs. Participants must have stable CNS metastases, adequate organ function, and no recent serious cardiovascular events. They should not be HIV or hepatitis positive and must agree to use contraception.Inclusion Criteria
Have you been diagnosed with Stage 3 or Stage 4 non-small cell lung cancer?
Has your disease progressed despite treatment?
Have you ever been a smoker?
+18 more
Exclusion Criteria
Have you ever been a smoker?
I do not have any active infections, lung issues, uncontrolled high blood pressure, diabetes, seizures, or other serious health problems.
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
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Lead-in
6 patients are enrolled and treated with LP-300 in combination with carboplatin and pemetrexed to assess safety
3 weeks
1 visit (in-person) per cycle
Treatment
Patients are randomized to receive either the investigational arm of LP-300 with carboplatin and pemetrexed or the standard of care arm of carboplatin and pemetrexed. Treatment occurs on Day 1 of a 21-day cycle for 4 to 6 cycles.
12-18 weeks
1 visit (in-person) per cycle
Maintenance
Patients may enter a pemetrexed maintenance phase after the initial treatment cycles
Variable
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the effectiveness of LP-300 combined with carboplatin and pemetrexed chemotherapy in improving survival without cancer progression compared to just chemotherapy alone. It's an open-label phase II trial involving 90 patients across multiple U.S. centers.
2Treatment groups
Experimental Treatment
Active Control
Group I: LP-300 in Combination with Pemetrexed and CarboplatinExperimental Treatment3 Interventions
LP-300 (investigational drug) + Pemetrexed and Carboplatin (standard of care chemotherapies)
Dosing occurs on Day 1 of a 21-day cycle.
Group II: Pemetrexed and Carboplatin (Standard of Care)Active Control2 Interventions
Pemetrexed and Carboplatin Only (standard of care chemotherapies)
Dosing occurs on Day 1 of a 21-day cycle.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NextGen OncologyBeverly Hills, CA
Inova Cancer InstituteFalls Church, VA
Texas OncologyDallas, TX
Comprehensive Cancer CenterFountain Valley, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Lantern Pharma Inc.Lead Sponsor
References
Role of pemetrexed in non-small cell lung cancer. [2022]Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells.
Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]The objective of this study was to evaluate the efficacy and safety of pemetrexed plus cisplatin/carboplatin in locally advanced or metastatic non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy.
Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. [2015]Pemetrexed is a multitargeted antifolate initially approved as a single agent for the second-line treatment of locally advanced or metastatic non-small cell lung cancer and more recently in the first-line setting combined with cisplatin. The combination of pemetrexed with carboplatin has been tested in several phase II clinical trials showing interesting antitumour activity with mild toxicity. Supplementation with folic acid and vitamin B12 during treatment with pemetrexed is recommended to reduce potential haematological and gastrointestinal adverse events.
Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. [2023]Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial.
Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%-23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy, respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%-44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in NSCLC has a response rate of less than 25%. The major toxicity associated with pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate nutritional supplement. Additional studies with pemetrexed in combination with other agents are needed for the treatment of NSCLC patients.
FDA drug approval summaries: pemetrexed (Alimta). [2022]The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]The novel multitargeted antimetabolite pemetrexed (Alimta), recently approved by the US Food and Drug Administration for the treatment of mesothelioma when combined with cisplatin, is also active in first- and second-line non-small-cell lung cancer (NSCLC). In a phase III trial comparing single-agent pemetrexed vs docetaxel (Taxotere) as second-line therapy in advanced NSCLC, survival was shown to be comparable between these agents, but side effects were significantly less frequent and severe for patients who received pemetrexed. In the frontline setting, phase II studies have shown significant activity and a very favorable toxicity profile of the combination of pemetrexed with a platinum agent. Pemetrexed has been well tolerated at systemic doses as a radiosensitizer when given as concurrent chest radiation, and a phase I study is under way to assess its tolerability in combination with carboplatin (Paraplatin) in this setting. Pemetrexed is an important addition to the armamentarium of medicines used to treat thoracic malignancies, and merits study in combination with other drugs having novel mechanisms of action.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). [2015]The objective of this study was the retrospective evaluation of tolerability and activity of pemetrexed with carboplatin (AC) or cisplatin (AP) as neoadjuvant chemotherapy in a consecutive series of patients with malignant pleural mesothelioma (MPM).
Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]Chemotherapeutic intervention in advanced and metastatic non-small-cell lung cancer (NSCLC) has changed over the past 2 decades. The improvements offered by cisplatin (Platinol)-based regimens, though significant in terms of survival and quality of life, were modest at best. Carboplatin (Paraplatin), which possesses a toxicity profile favorable to that of its parent analogue cisplatin, yielded survival rates superior to that of the cisplatin-combination chemotherapy arms in a large randomized study of patients with metastatic non-small-cell lung cancer. With the introduction of taxanes in the early 1990s, paclitaxel (Taxol) demonstrated single-agent activity of 21% to 24%, with a 40% 1-year survival rate in metastatic disease. The next generation of phase I/II studies evaluated the efficacy of paclitaxel in combination with carboplatin. Results with this regimen have shown substantial promise, and 1-year survival rates as high as 54% have been reported. Full doses of both agents have been combined without any additional toxicity, and there appears to be a dose-response effect with paclitaxel. The combination of paclitaxel and carboplatin has been incorporated as the investigational arm of all the ongoing multicenter and cooperative group studies. While the results from these randomized studies are awaited, this combination has become the most widely used regimen in community practice for patients with non-small-cell lung cancer. It is also being evaluated for treatment at earlier disease stages, in the setting of minimal tumor burden, and in combined-modality regimens.
Carboplatin and paclitaxel for previously treated patients with non-small-cell lung cancer. [2019]The chemotherapy regimen of paclitaxel and carboplatin produces an objective response in 30%-60% of patients with non-small-cell lung cancer (NSCLC). In a prospective study, we administered paclitaxel 200 mg/m2 (by 1-3-hr infusion) and carboplatin at an area under the plasma concentration curve (AUC) of 5 (by the Calvert formula) every 3 weeks to 21 patients who had previously received predominantly platinum-based chemotherapy for NSCLC. We observed no objective responses. Patients received a median of 2 cycles before disease progression. Three of 5 patients who had received only single-agent treatment with a relatively inactive agent may have had modest clinical benefit. We conclude that the paclitaxel/carboplatin regimen has minimal activity in previously treated patients with NSCLC.
A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. [2022]Paclitaxel-carboplatin is used as the standard regimen for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was designed to compare gemcitabine + carboplatin or gemcitabine + paclitaxel to the standard regimen.
Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]Based on their good activity and minimal toxicity in non-small cell lung cancer and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51 patients treated, the overall response rate was 27.5% (14 partial responses). Seventeen patients had stable disease, while 16 patients experienced disease progression after two cycles of treatment. Apart from myelosuppression, toxicity has been modest, with fewer than 5% of patients experiencing grade 3 or greater nonhematologic toxicity. Objective response and survival rates were modestly improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135 mg/m2). These data suggest that paclitaxel plus carboplatin warrants further study in metastatic non-small cell lung cancer.