Combination Therapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: UNC Lineberger Comprehensive Cancer Center
Disqualifiers: Organ transplant, others
Stay on Your Current Meds
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
Non-Small Cell Lung Cancer (NSCLC) is one of the deadliest types of cancer. In lung cancer patients with a tumor that can be removed by surgery, adjuvant chemotherapy increases survival. Neoadjuvant therapy may have advantages such as, it may be more tolerable prior to surgery, earlier treatment may be more efficacious, and it can provide an indication of treatment response. Neoadjuvant treatment can provide pre- and post-treatment specimens for correlative analysis to better understand mechanisms of action and resistance. This pilot study will investigate the effects of neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist, in subjects with NSCLC who are scheduled to undergo surgical resection as part of their standard of care. The purpose of this study is to study how well using a combination of durvalumab, platinum doublet chemotherapy (carboplatin/abraxane or carboplatin/pemetrexed), and abequolixron treats non-small cell lung cancer before surgery. Durvalumab (a type of immunotherapy) and platinum doublet chemotherapy are drugs that are individually approved for use during the treatment of cancer. FDA (Food and Drug Administration) has not approved the combined use of these drugs in treating non-small cell lung cancer. Abequolixron is not FDA approved for the treatment of cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving other chemotherapy, investigational products, or biologic or hormonal therapy for cancer treatment, except for those mentioned in the trial.
What data supports the effectiveness of the drug combination therapy for lung cancer?
Research shows that combinations including pemetrexed and carboplatin have demonstrated effectiveness in treating advanced non-small-cell lung cancer (NSCLC), as seen in studies like PointBreak and PRONOUNCE. These studies highlight the potential of these drugs in improving outcomes for patients with this type of lung cancer.12345
Is the combination therapy for lung cancer generally safe in humans?
The combination therapy involving carboplatin has been studied in various trials and is generally considered to have an acceptable safety profile, though it can cause side effects like thrombocytopenia (low platelet count) and leukopenia (low white blood cell count). Other side effects may include nausea and vomiting, but significant kidney, ear, or nerve damage was not observed in these studies.678910
How is the combination therapy of Carboplatin and Durvalumab unique for lung cancer treatment?
The combination of Carboplatin and Durvalumab (Imfinzi) for lung cancer is unique because it combines a chemotherapy drug (Carboplatin) with an immunotherapy drug (Durvalumab), which helps the immune system recognize and attack cancer cells. This approach is different from traditional chemotherapy alone, as it aims to enhance the body's natural defenses against cancer.19111213
Eligibility Criteria
This trial is for adults over 18 with non-small cell lung cancer that can be surgically removed. They must weigh more than 40 kg, have a good performance status (able to carry out daily activities), and not be on other cancer treatments except those in the study.Inclusion Criteria
I am fully active or can carry out light work.
My lung cancer is confirmed and surgery is recommended.
You weigh more than 40 kilograms.
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Exclusion Criteria
I am not on any cancer treatments except those allowed in this study or hormone therapy for non-cancer reasons.
Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
You have had an organ transplant from another person.
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Treatment Details
Interventions
- Abequolixron (Other)
- Abraxane (Chemotherapy)
- Carboplatin (Chemotherapy)
- Durvalumab (Checkpoint Inhibitor)
- Pemetrexed (Chemotherapy)
Trial OverviewThe study tests how well non-small cell lung cancer responds before surgery to durvalumab (immunotherapy) plus chemotherapy (carboplatin with abraxane or pemetrexed), and when combined with an experimental drug called abequolixron.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant therapyExperimental Treatment5 Interventions
Subjects with operable Non-Small Cell Lung Cancer received neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist.
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:
UNC Lineberger Comprehensive Cancer CenterChapel Hill, NC
Fox Chase Cancer CenterPhiladelphia, PA
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
UNC Lineberger Comprehensive Cancer CenterLead Sponsor
Rgenix, Inc.Industry Sponsor
AstraZenecaIndustry Sponsor
References
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.
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).
Carboplatin/pemetrexed/bevacizumab in the treatment of patients with advanced non-small-cell lung cancer: a single-institution experience. [2022]The purpose of this study was to determine the efficacy and tolerability of carboplatin, pemetrexed, and bevacizumab in patients with advanced, nonsquamous non-small-cell lung cancer (NSCLC).
Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). [2020]The aim of this study was to evaluate the activity and toxicity of pemetrexed and carboplatin combination as first-line chemotherapy in malignant pleural mesothelioma (MPM).
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).
Phase II study of carboplatin in patients with nonresected lung cancer. Japan Cooperative Oncology Group on Lung Cancer. [2019]A multicenter phase II trial of carboplatin, a new platinum analog of cisplatin, was carried out in bronchogenic carcinoma at 17 institutions throughout Japan. Of 139 patients enrolled in this trial, 10 were excluded from analysis as inevaluable and the remaining 129 were judged to be evaluable for response and toxic effects by the Extramural Review Committee. Patients were treated i.v. with either 300 or 400 mg/m2 carboplatin every 4 weeks. Responses and toxic effects were assessed at both dose levels. The overall response rate was 17.8% (23/129), with response rates of 28.4% (19/67) for small-cell disease, 7.1% (2/28) for squamous-cell carcinoma, and 6.9% (2/29) for adenocarcinoma. The most frequent toxic effects were thrombocytopenia and leukopenia, with a platelet count of less than 7 x 10(4) microliters recorded in 60 patients (46.5%) and a WBC count of less than 3,000/microliters recorded in 60 cases (46.5%). Vomiting occurred in 28 patients (21.7%). Renal, aural, and neurotoxicities were not seen. Hydration was not required. Carboplatin was demonstrated to be active against lung cancer, especially against small-cell lung cancer.
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.
Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. [2017]Cisplatin (NSC 119875) and carboplatin (NSC 241240) are platinum (II) analogues with very different spectra of toxicity. Cisplatin dose is limited by nausea and vomiting, renal dysfunction, and dose-related peripheral neuropathy, whereas carboplatin is myelosuppressive. There are also clinical and laboratory data that suggest that these drugs may not be completely cross-resistant. Therefore, the following phase I trial of combination therapy with cisplatin and carboplatin was undertaken. Since carboplatin toxicity is enhanced in the presence of renal impairment, carboplatin excretion was also evaluated in selected patients at the maximum tolerated dose. Thirty-three patients received 50 mg/m2 cisplatin and doses of carboplatin between 160 mg/m2 and 400 mg/m2. Sequential 20-minute infusions of carboplatin and then cisplatin were able to be administered at the standard doses of carboplatin (320 and 400 mg/m2) with thrombocytopenia to the degree expected if carboplatin alone had been given. However, 280 mg/m2 carboplatin followed by 25 mg/m2 cisplatin/d X 3 caused unexpectedly severe thrombocytopenia in seven of eight patients (median platelet nadir 45,000/microL; range, 12 to 321,000/microL; nadir was less than 90,000 in seven of eight patients). In three patients treated with 280 mg/m2 carboplatin plus 25 mg/m2/d X 3 cisplatin, pharmacokinetics of carboplatin were compared during consecutive monthly cycles without and with cisplatin. Modestly increased areas under the curve (AUC) for carboplatin (15% and 35%) with cisplatin were seen in the two patients who experienced more pronounced platelet suppression with combination therapy. No other limiting or unusual toxicity was seen with this combination. Responses, primarily in "platinum responsive" tumors, were seen. The combination of cisplatin plus carboplatin is feasible and merits further study.
Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. [2018]Since 1984, the Respiratory Committee of the Cancer and Leukemia Group B (CALGB) has evaluated carboplatin, either alone or in combination, in five separate phase II studies for patients with inoperable non-small cell lung cancer (NSCLC). All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had not received previous treatment with chemotherapy. In 70 patients with stage IIIB or IV disease, carboplatin 400 mg/m2 administered intravenously once every 4 weeks produced a 16% overall response rate and an acceptable toxicity profile. Subsequently, combinations of carboplatin/cisplatin, carboplatin/etoposide, and carboplatin/vinblastine have been evaluated in similar patient groups. Response rates of 11%, 12%, and 20%, respectively, were obtained. Myelosuppressive toxicity was substantially greater with carboplatin/etoposide and carboplatin/vinblastine than with carboplatin alone. Carboplatin/vinblastine demonstrated efficacy similar to that of the cisplatin/vinblastine combination previously evaluated by CALGB for treatment of similar patients with advanced NSCLC; ease of administration and lack of significant nephrotoxicity also compared favorably with cisplatin-based therapy. In regional NSCLC patients, carboplatin 100 mg/m2/wk can be administered intravenously concurrently with 60 Gy thoracic radiotherapy given over 6 weeks. The impact of concurrent carboplatin added to a sequential chemotherapy-radiotherapy program for patients with regional NSCLC is currently under study by the CALGB Respiratory Committee.
[Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer]. [2022]To observe the clinical efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC).
Docetaxel in combination with platinum compounds for non small-cell lung cancer. [2019]Assessing the combination of docetaxel with cisplatin or carboplatin was based on their activity as single agents, their nonoverlapping toxicity profiles, and their lack of cross-resistance. Phase I studies of docetaxel in combination with cisplatin established that 75 mg/m2 of each agent could be administered with reasonable safety and appeared to be active in non small-cell lung cancer (NSCLC). We evaluated the docetaxel/cisplatin combination in patients with advanced NSCLC. The response rate was 32%, and the median survival was 11.5 months. Efficacy was comparable to that observed in the Australian and French trials with the same combination. This is now being evaluated further in two large randomized trials for patients with advanced NSCLC and has been incorporated into the combined modality programs for early-stage disease. Carboplatin, devoid of the nephrotoxicity and neurotoxicity associated with the parent cis-platin, was then combined with docetaxel. The recommended dose of docetaxel for further evaluation in combination with carboplatin (AUC=6 mg/mL.min) was 90 mg/m2 with filgrastim support and 80 mg/m2 without filgrastim support. Our phase II trial of the combination of docetaxel and carboplatin in advanced NSCLC demonstrated an overall response rate of 36%; median survival was 13.9 months, and 1-year survival was 52%. Comparable activity has been seen by other investigators, and the regimen is being evaluated in two randomized trials. The combination of docetaxel with either of the two platinum agents has reasonable activity in NSCLC, though the carboplatin/docetaxel doublet appears to have a better therapeutic index.
Phase II studies with carboplatin in non-small cell lung cancer. [2018]Since 1987, we have evaluated carboplatin alone or in combination with etoposide in two separate phase II trials of patients with non-small cell lung cancer (NSCLC) who had not received prior chemotherapy. Single-agent carboplatin produced a 20% response rate in 51 patients treated with 390 mg/m2 intravenously every 4 weeks. A 3-day schedule of etoposide 140 mg/m2 on days 2, 3, and 4, and carboplatin 150 mg/m2 on days 1 and 5 also resulted in a 26.7% response rate in 46 patients. Myelosuppressive toxicity associated with carboplatin/etoposide was substantially greater than that seen with carboplatin alone. Carboplatin as a single agent is active in previously untreated patients with advanced NSCLC. The two-drug combination of carboplatin and etoposide also shows activity in NSCLC similar to other combination chemotherapeutic regimens based on comparable prognostic factors in untreated patients. Further evaluation of carboplatin as part of combination chemotherapy in NSCLC is warranted.
Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial. [2022]Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial.