Sotorasib + Chemotherapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Warfarin, CYP3A4 inducers
Disqualifiers: Squamous NSCLC, Hematological malignancies, Cardiovascular disease, Gastrointestinal disease, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This is a phase II, single-arm, open-label study evaluating the efficacy, safety and tolerability of neoadjuvant sotorasib in combination with cisplatin (or carboplatin) and pemetrexed chemotherapy for patients with surgically resectable stage IIA - IIIB (T3-T4/N2) (based on AJCC 8th edition), non-squamous NSCLC with a KRAS p.G12C mutation. The primary objective of the study is to determine whether neoadjuvant therapy with 4 cycles of at least one dose of sotorasib plus cisplatin (or carboplatin) and pemetrexed can be administered safely and result in improved MPR rate in patients with KRAS p.G12C-mutant non-squamous NSCLC compared with the historical control MPR rate for platinum-based chemotherapy alone.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, certain medications like strong inducers of CYP3A4, warfarin, and some others may need to be reviewed and approved by the principal investigator. It's best to discuss your current medications with the study team.
What data supports the effectiveness of the drug combination of Sotorasib, Carboplatin, Cisplatin, and Pemetrexed for lung cancer?
Research shows that combining pemetrexed with either cisplatin or carboplatin has been effective in treating non-small cell lung cancer (NSCLC), leading to significant survival benefits. Additionally, the combination of pemetrexed and carboplatin has shown promising antitumor activity with mild side effects in advanced NSCLC.12345
Is the combination of Sotorasib and chemotherapy safe for humans?
The combination of pemetrexed with cisplatin or carboplatin, which are chemotherapy drugs, has been studied for safety in lung cancer patients. Common side effects include fatigue, blood-related issues, digestive problems, and skin reactions. These studies suggest that while the treatment can be effective, it may also cause significant side effects.26789
What makes the drug combination of Sotorasib and chemotherapy unique for lung cancer treatment?
The combination of Sotorasib with chemotherapy for lung cancer is unique because Sotorasib specifically targets a mutation in the KRAS gene, which is common in certain lung cancers, while the chemotherapy drugs like Carboplatin, Cisplatin, and Pemetrexed are used to kill cancer cells more broadly. This targeted approach, combined with traditional chemotherapy, may offer a more effective treatment option for patients with specific genetic profiles.110111213
Eligibility Criteria
This trial is for adults over 18 with stage IIA-IIIB non-squamous NSCLC, who haven't been treated before and have a KRAS p.G12C mutation. They must be fit for surgery, have good kidney function, an ECOG score of 0-1 (which means they're fully active or restricted in physically strenuous activity but can do light work), and no signs of stage IV cancer. Participants need to provide tissue samples, not be pregnant or breastfeeding, use effective contraception if applicable, and cannot have certain health issues that would interfere with the study.Inclusion Criteria
My cancer is between stages IIA and select IIIB.
I can take pills and am willing to track my medication use daily.
My blood and liver tests are within normal ranges.
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Exclusion Criteria
I agree not to donate sperm during my treatment.
I haven't needed strong antibiotics for infections in the last 2 weeks.
I have not had major surgery in the last 4 weeks.
See 21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive neoadjuvant sotorasib in combination with cisplatin (or carboplatin) and pemetrexed for 4 cycles
12 weeks
Surgery
Participants undergo surgical resection of the tumor
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Treatment Details
Interventions
- Carboplatin (Alkylating agents)
- Cisplatin (Alkylating agents)
- Pemetrexed (Anti-metabolites)
- Sotorasib (Small Molecule)
Trial OverviewThe trial tests sotorasib combined with cisplatin (or carboplatin) and pemetrexed as pre-surgery treatment for lung cancer patients. The goal is to see if this combination improves the rate at which tumors shrink compared to historical data on chemotherapy alone. Patients will receive four cycles of treatment including at least one dose of sotorasib.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Sotorasib in Combination with Cisplatin/Carboplatin and PemetrexedExperimental Treatment4 Interventions
4 cycles of at least one dose of sotorasib plus cisplatin (or carboplatin) and pemetrexed can be administered safely
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:
Memorial Sloan Kettering Cancer CenterNew York, NY
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
AmgenIndustry Sponsor
References
Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. [2015]Given the activity and tolerability of pemetrexed/platinum combinations in non-small-cell lung cancer, and the success of novel therapeutic strategies employed in recent extensive-stage small-cell lung cancer (ES-SCLC) trials, a randomized phase II trial was initiated to evaluate the use of cisplatin or carboplatin plus pemetrexed in previously untreated ES-SCLC.
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.
Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]Platinum-based chemotherapy has long been the first-line treatment of choice for metastatic non-small-cell lung cancer (NSCLC) patients who lack targetable gene mutations. The arrival of checkpoint blockade has led to a vast shift in the treatment landscape of NSCLC. Among NSCLC patients with PD-L1 expression in ≥50% of tumor cells, treatment with pembrolizumab leads to a superior progression-free and overall survival compared to platinum-doublet chemotherapy in the first-line setting. Furthermore, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significant longer progression-free survival and overall survival irrespective to PD-L1 expression. In this review, we focus on the molecular rationale for the combination therapy and the results of completed clinical studies.
Cisplatin versus carboplatin in NSCLC: is there one "best" answer? [2022]Platinum-based chemotherapeutic doublets have produced significant survival benefits for patients with non-small cell lung cancer of all disease stages. The optimal combination of chemotherapy has been the subject of much investigation, and the ideal platinum agent the subject of ongoing and heated debate. For patients with resected disease, all evidence of survival advantage rests with cisplatin, and the only clinical trial to evaluate carboplatin-based therapy failed to show a survival benefit. In the setting of locally advanced lung cancer, no comparative data exist, and even randomized phase III trials are largely lacking. Cisplatin-based doublets provide the most consistent evidence of superior survival when coupled with definitive thoracic radiation. Meta-analyses of palliative chemotherapy indicate consistent survival advantages with cisplatin-based therapy over carboplatin; however, the relative advantage is small. Cisplatin carries a higher toxicity profile, including nausea, vomiting, neuropathy, renal insufficiency, and alopecia in comparison to carboplatin. When the goal of therapy is curative, the survival benefits with cisplatin are in most circumstances worth the increased toxicities. When the goal of therapy is palliation, the relative price of toxicity needs to be weighed on the basis of the individual patient in an effort to maximize quality of life.
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.
Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. [2018]This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer.
Non-steroidal anti-inflammatory drugs induce severe hematologic toxicities in lung cancer patients receiving pemetrexed plus carboplatin: A retrospective cohort study. [2022]As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients.
Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome. [2015]Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees.
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).
Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. [2019]In scheduling chemotherapy and radiotherapy for locally advanced non-small cell lung cancer (NSCLC), chemotherapy can be given pre-radiotherapy or concurrently as a single agent or in combination. Optimal scheduling has yet to be established. Optimal pre-radiotherapy for NSCLC requires further development but cisplatin with vinblastine, vindesine, etoposide or navelbine appear the best currently available. A number of new drugs show potential for enhancing radiation effects. Concurrent chemotherapy and radiotherapy has been tested in a number of experimental tumours in cell culture. In these systems cisplatin, carboplatin, 5-fluorouracil, mitomycin-C and other agents appear to improve cell kill compared to chemotherapy alone. Mouse xenograft models allow the study of various concurrent drug and radiation schedules including the effect of radiation with cisplatin, carboplatin, paclitaxel and gemcitabine. In these systems, cisplatin in divided doses shows optimal enhancement with fractionated radiotherapy. There are a number of drug candidates for concurrent chemotherapy and radiotherapy programs. Clinical studies in head and neck cancer, esophageal cancer, small cell lung cancer and NSCLC show promising results with concurrent chemotherapy and radiotherapy. Cisplatin given daily with radiotherapy improved survival in NSCLC compared to cisplatin given weekly with radiotherapy or to radiotherapy alone. To study the toxicity of radiation and concurrent carboplatin, we have studied 170 patients with unresectable locally advanced NSCLC in a 4-arm randomized trial. An analysis of the first 100 patients entered revealed significantly more neutropenia (P
[Chemotherapy for non-small cell lung cancer]. [2018]The combination of cisplatin and either a vinca alkaloid or etoposide is one of the most effective chemotherapeutic regimens for non-small cell lung cancer. Meta-analyses of clinical trials in which cisplatin-based combination chemotherapy was compared with supportive care in patients with non-resectable non-small cell lung cancer showed that the chemotherapy reduced mortality. In the last decade, new agents, including vinorelbine, edatrexate, paclitaxel, docetaxel, irinotecan, topotecan and gemcitabine, have shown promise in the treatment of non-small cell lung cancer, and new agents combined with platinum compounds have reached the level of phase III testing. Randomized studies in which radiotherapy alone was compared with radiotherapy and cisplatin-based combination chemotherapy in patients with stage III disease showed that combined treatment can prolong survival and improve long-term outcome in patients with locally advanced non-small cell lung cancer. Recently, new agents combined with radiotherapy have been tested. Regimens in which platinum compounds are combined with new agents hold promise for more successful treatment of this disease.
Carboplatin, vindesine, 5-fluorouracil-leucovorin and 13-cis retinoic acid in the treatment of advanced non-small cell lung cancer. A phase II study. [2013]Carboplatin, vindesine and 5-fluorouracil/leucovorin are drugs active in the treatment of non-small cell lung cancer (NSCLC) and they can be administered in an outpatient setting. Retinoids, which are widely used agents in chemoprevention, have been reported to exert (in vitro models) growth inhibitory effects of synergistic type with chemotherapy, and differentiating effects on NSCLC cells.
Pemetrexed in second line of non-small cell lung cancer. [2015]Non small cell lung cancer (NSCLC), which is the leading cause of cancer mortality, is accounts for 85% of all cases of lung cancer. The majority of NSCLC patients present with advanced, unresectable disease. In advanced disease, chemotherapy with platinun (cisplatin or carbo-platin) in combination with a third-generation cytotoxic drug (gemcitabine, vinorelbine, paclitaxel or docetaxel) can provide a modest improvement in survival with quality of life. Response rates of 20%-40% can be expected with a median survival of 8-10 months and a 1 year survival rate of 30% - 40%. Pemetrexed, a multitargeted antifolate agent, has shown clear activity in mesothelioma and NSCLC. In a phase III trial, second line treatment with pemetrexed demonstrated overall survival comparable to docetaxel with a more manageable toxicity profile. Single agent pemetrexed have shown well tolerate in elderly patients, in combination with radiotherapy where we can use full dose pemetrexed. In second line, in nonsquamous NSCLC pemetrexed administrated with folic acid and vitamin B12, has a significant superior survival compared with docetaxel (9.3 vs 8.0months). Rev Port Pneumol 2008; XIV (Sup.2): S21-S26.