Carboplatin + Taxane + Ramucirumab for Non-Small Cell Lung Cancer

Overseen By Melissa Volpe, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: Driver mutation, Other malignancy, Neuropathy, Brain metastases, Bleeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 3 years

59 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if the combination of the three anti-cancer drugs carboplatin, paclitaxel, and ramucirumab is helpful in shrinking tumors or delaying tumor growth in participants with non-small cell lung cancer. This study will also assess whether it is safe to combine these drugs.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it seems likely that you may need to stop certain cancer treatments, especially if they conflict with the trial drugs.

What data supports the effectiveness of the drug combination Carboplatin, Paclitaxel, and Ramucirumab for treating non-small cell lung cancer?

Research shows that the combination of Carboplatin and Paclitaxel has been effective in treating advanced non-small cell lung cancer, with response rates up to 36% and a 1-year survival rate of 42%. This suggests that adding Ramucirumab, which is known to work well with similar drugs, could potentially enhance the treatment's effectiveness. ^{1 2 3 4 5}

Is the combination of Carboplatin, Paclitaxel, and Ramucirumab safe for treating non-small cell lung cancer?

The combination of Carboplatin and Paclitaxel has been studied for non-small cell lung cancer and is generally considered safe, with some patients experiencing mild to moderate side effects like myelosuppression (a decrease in bone marrow activity) and neuropathy (nerve damage). Nab-paclitaxel, a form of Paclitaxel, showed fewer side effects like neutropenia (low white blood cell count) and neuropathy compared to the solvent-based version. However, specific safety data for the combination with Ramucirumab is not provided in the available research. ^{1 2 4 6 7}

How is the drug combination of Carboplatin, Paclitaxel, and Ramucirumab unique for treating non-small cell lung cancer?

This drug combination is unique because it combines Carboplatin and Paclitaxel, which are widely used for their effectiveness and manageable side effects, with Ramucirumab, an anti-angiogenic agent that targets blood vessel growth in tumors. This combination aims to enhance survival rates by attacking the cancer through multiple mechanisms, offering a novel approach compared to standard treatments. ^{1 2 8 9 10}

Research Team

Melina Marmarelis, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

Adults with advanced non-squamous NSCLC (Stage IV or recurrent) who have had 4-6 cycles of Pem/Carbo/Pembro and disease progression after at least 18 weeks on maintenance Pemetrexed, Pembrolizumab, or both. Participants must be in good physical condition (PS 0-1). Not eligible if they have treatable mutations, other cancers needing treatment, moderate to severe sensory neuropathy, untreated brain metastases, or a history of significant bleeding.

Inclusion Criteria

I am fully active or can carry out light work.

I've had 4-6 cycles of Pem/Carbo/Pembro and my condition worsened after 18 weeks on maintenance therapy.

I am 18 or older with advanced non-squamous NSCLC.

Exclusion Criteria

I have not coughed up significant blood recently.

I have moderate to severe numbness or pain in my hands or feet.

My cancer has a mutation that can be treated with targeted therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Carboplatin, Paclitaxel, and Ramucirumab to assess tumor response and safety

3 years

Every 3 weeks

Follow-up

Participants are monitored for progression-free survival and overall survival

1-2 years

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Ramucirumab

Trial Overview The trial is testing the effectiveness and safety of combining three drugs: Carboplatin, Paclitaxel, and Ramucirumab for patients with NSCLC who've previously been treated with Pemetrexed or Pembrolizumab. The goal is to see if this drug combo can shrink tumors or slow their growth.

Participant Groups

Group I: Carboplatin, Taxane And Ramucirumab Experimental Treatment 3 Interventions

Carboplatin AUC 5 IV every 3 wks, Paclitaxel 80 mg/m2 IV days 1 and 8 every 3 weeks, and Ramucirumab 10 mg/kg IV every 3 weeks

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

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Findings from Research

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

In a phase II study involving 53 patients with advanced non-small cell lung cancer, the combination of cetuximab, paclitaxel, and carboplatin resulted in a response rate of 57%, indicating significant clinical activity.

The treatment was well tolerated with manageable toxicities, including rash and neutropenia, and no grade 5 toxicities reported, suggesting a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel, carboplatin, and cetuximab as first line treatment, for patients with advanced non-small cell lung cancer (NSCLC): results of OPN-017. Borghaei, H., Langer, CJ., Millenson, M., et al.[2018]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase II study involving 155 patients with advanced non-small-cell lung cancer, the combination of paclitaxel and carboplatin resulted in a 34% objective response rate, indicating significant efficacy in treating this cancer type.

The treatment was generally safe, with manageable side effects like leukopenia and peripheral neuropathy, and a median survival of 8 months, along with a 1-year survival rate of 42%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. Greco, FA., Hainsworth, JD.[2015]

In a study of patients with advanced non-small cell lung cancer receiving carboplatin and nanoparticle albumin-bound paclitaxel, 55% experienced treatment suspension, primarily due to neutropenia (65.2%) and infections (24.2%).

Baseline liver dysfunction, age 65 or older, and a performance status of 2 were identified as significant risk factors for treatment suspension, highlighting the need for careful monitoring in these patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. Saito, Y., Takekuma, Y., Shinagawa, N., et al.[2022]

Nab-paclitaxel (Abraxane(®)) combined with carboplatin has been approved for treating advanced non-small-cell lung cancer (NSCLC) and showed a significantly improved overall response rate compared to traditional solvent-based paclitaxel in a Phase III trial.

Patients receiving nab-paclitaxel experienced fewer side effects such as neutropenia and neuropathy, making it a safer option, although it was associated with more thrombocytopenia and anemia compared to solvent-based paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. Hirsh, V.[2022]

In a phase II study involving 160 Japanese patients with non-small cell lung cancer (NSCLC), the combination of ramucirumab and docetaxel significantly prolonged progression-free survival (PFS) compared to placebo-docetaxel, with a median PFS of 5.22 months versus 4.21 months.

While overall survival rates were similar between the two groups, the ramucirumab-docetaxel combination showed a higher objective response rate (28.9% vs 18.5%) and a higher disease control rate (78.9% vs 70.4%), although it was associated with a higher incidence of febrile neutropenia (34.2% vs 19.8%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy. Yoh, K., Hosomi, Y., Kasahara, K., et al.[2023]

Ramucirumab, an anti-VEGFR2 agent, has been shown to improve progression-free and overall survival in patients with Non-Small Cell Lung Cancer (NSCLC) when combined with docetaxel, particularly benefiting those with more aggressive tumors.

While treatment with ramucirumab is generally tolerable, it carries risks of severe adverse effects such as neutropenia, febrile neutropenia, hypertension, and potential bleeding, highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab in the treatment of non-small cell lung cancer. Arrieta, O., Zatarain-Barrón, ZL., Cardona, AF., et al.[2023]

Ramucirumab, approved by the FDA for treating metastatic non-small cell lung cancer (NSCLC), significantly improves overall survival when combined with docetaxel, showing a median survival of 10.5 months compared to 9.1 months with placebo in a study of 1,253 patients.

The treatment has an acceptable safety profile, with common side effects including fatigue, neutropenia, and diarrhea, although some patients experienced more severe reactions like febrile neutropenia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Ramucirumab for the Treatment of Metastatic Non-Small Cell Lung Cancer Following Disease Progression On or After Platinum-Based Chemotherapy. Larkins, E., Scepura, B., Blumenthal, GM., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel, carboplatin, and cetuximab as first line treatment, for patients with advanced non-small cell lung cancer (NSCLC): results of OPN-017. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

5. United States pubmed.ncbi.nlm.nih.gov

One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Ramucirumab in the treatment of non-small cell lung cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Ramucirumab for the Treatment of Metastatic Non-Small Cell Lung Cancer Following Disease Progression On or After Platinum-Based Chemotherapy. [2023]