DoceRamPem for Lung Cancer

(DoceRamPem Trial)

Recruiting at 1 trial location

Overseen By Lauren Collins, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, Brain metastasis, Cardiovascular, 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: 1

Duration: Up to 6 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 2 trial will evaluate the safety and efficacy of combining immunotherapy with a PD-1 checkpoint inhibitor (Pembrolizumab), an anti-VEGF receptor (Ramucirumab), and a taxane chemotherapy (Docetaxel) in treating patients with non-small cell lung cancer (NSCLC) who did not respond to FDA-approved treatments with platinum-based chemotherapy given concurrently or sequentially with anti-PD1/PD-L1 immunotherapy. Pembrolizumab helps the body's immune system to attack cancer cells and hinder their ability to grow and spread. Ramucirumab blocks new blood vessel growth to reduce tumor growth. Docetaxel works mainly by stopping cancer cells from dividing. Ramucirumab combined with docetaxel is an FDA-approved therapy for NSCLC patients after progression on platinum-based chemotherapy. It has shown to improve efficacy compared to docetaxel alone in this setting. Pembrolizumab is an FDA-approved treatment for NSCLC and can be given alone or in combination with platinum-based chemotherapy. Investigators hypothesize that the combination of docetaxel, ramucirumab, and pembrolizumab will be safe and more effective than the current standard of care treatments (docetaxel alone or in combination with ramucirumab) in patients with metastatic or recurrent NSCLC after progression on treatment with platinum-based chemotherapy and immunotherapy, given concurrently or sequentially.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any systemic anti-cancer therapy within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

What data supports the effectiveness of the drug combination used in the DoceRamPem trial for lung cancer?

Research shows that combining ramucirumab with docetaxel can improve survival in patients with advanced non-small cell lung cancer who have already tried other treatments. This combination has been approved by the FDA and has shown to extend life by about 1.4 months in these patients. ^{1 2 3 4 5}

Is the combination of ramucirumab and docetaxel safe for treating lung cancer?

The combination of ramucirumab and docetaxel has been shown to have an acceptable safety profile in patients with advanced non-small cell lung cancer, with common side effects including fatigue, low white blood cell counts (neutropenia), and diarrhea. Serious side effects can include severe fatigue, very low white blood cell counts with fever (febrile neutropenia), low white blood cell counts (leukopenia), and high blood pressure (hypertension). ^{1 2 6 7 8}

What makes the DoceRamPem drug unique for lung cancer treatment?

The DoceRamPem drug combines docetaxel, ramucirumab, and pembrolizumab, offering a novel approach by integrating a chemotherapy agent, a vascular endothelial growth factor receptor-2 inhibitor, and an immune checkpoint inhibitor. This combination aims to enhance treatment effectiveness for non-small cell lung cancer, especially in patients who have progressed after standard therapies. ^{1 3 6 9 10}

Research Team

Badi El Osta, MD, FACP

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with non-small cell lung cancer (NSCLC) who didn't respond to platinum-based chemo and PD-1/PD-L1 inhibitors. They should have manageable heart conditions, adequate blood counts, measurable disease, agree to contraception use, and not be pregnant or breastfeeding. Prior cancers are okay if they don't affect this study's safety or results. Participants need a life expectancy over 12 weeks and must have recovered from previous cancer treatments.

Inclusion Criteria

My cancer has worsened after treatment with platinum chemotherapy and PD-1/PD-L1 inhibitors.

Your liver enzyme levels are within a certain range, or slightly higher if you have cancer that has spread to the liver.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

I stopped using immune therapy due to side effects treated with steroids.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive docetaxel, ramucirumab, and pembrolizumab intravenously on day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Up to 6 months

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival follow-up every 12 weeks for 2 years, then every 6 months for 3 years, then annually

Up to 10 years

Telephone follow-up

Treatment Details

Interventions

• Docetaxel
• Pembrolizumab
• Ramucirumab

Trial Overview The trial tests combining Pembrolizumab (an immunotherapy), Ramucirumab (blocks blood vessel growth in tumors), and Docetaxel (a chemotherapy drug). It aims to see if this mix is safer and works better than the current standard care after NSCLC patients' disease progresses following specific prior treatments.

Participant Groups

Group I: Treatment (docetaxel, ramucirumab, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive docetaxel IV over 60 minutes, ramucirumab IV over 60 minutes, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Ramucirumab, when combined with docetaxel, improves overall survival by 1.4 months for patients with metastatic non-small cell lung cancer (NSCLC) who have progressed after platinum-based chemotherapy.

The treatment has an acceptable safety profile, but its role may be influenced by the introduction of PD-1-blocking antibodies like nivolumab or pembrolizumab in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. Takeda, K., Daga, H.[2023]

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]

In a study involving 25 patients with advanced non-small cell lung cancer and asymptomatic brain metastases, the combination of ramucirumab and docetaxel showed a median progression-free survival of 3.9 months and a median overall survival of 20.9 months, indicating potential efficacy for this patient group.

The treatment was generally well-tolerated, with no severe adverse events like intracranial hemorrhage reported, although 40% of patients experienced grade 3 or higher neutropenia, suggesting that while the combination is promising, further studies with larger sample sizes are necessary to fully assess safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab Plus Docetaxel for Patients with Non-small cell Lung Cancer with Brain Metastases: A Multicenter, Open-Label Single-Arm Phase II Trial. Tanimura, K., Uchino, J., Kimura, H., et al.[2023]

In a study of 99 patients with non-small cell lung cancer (NSCLC), the combination of docetaxel (DTX) and ramucirumab (Ram) significantly improved progression-free survival (PFS) in patients who had previously received anti-PD-1/L1 therapy, with a median PFS of 5.9 months compared to 2.8 months for DTX alone.

In patients who had not received anti-PD-1/L1 therapy, there was no significant difference in PFS or overall survival (OS) between those treated with DTX alone and those treated with DTX plus Ram, suggesting that Ram may specifically enhance DTX efficacy after prior immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment. Tozuka, T., Kitazono, S., Sakamoto, H., et al.[2023]

In a study of 288 patients with advanced non-small cell lung cancer (NSCLC), extended treatment with immune checkpoint inhibitors (ICIs) for more than 180 days and maintenance therapy were identified as significant predictors of improved progression-free survival (PFS) and overall survival (OS) when transitioning to ramucirumab plus docetaxel (RD) as second-line therapy.

The analysis showed that factors like performance status and histology (specifically adenocarcinoma) also independently predicted better outcomes after RD treatment, while the therapeutic response and PD-L1 expression were not closely linked to the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended ICI treatment after first-line chemoimmunotherapy could predict the clinical benefit of ramucirumab plus docetaxel in advanced non-small lung cancer: Post hoc analysis from NEJ051 (REACTIVE study). Yamaguchi, O., Mori, K., Takata, S., 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]

In a study of 114 patients with advanced non-small cell lung cancer, the combination of ramucirumab and docetaxel (RAM+DOC) showed similar efficacy in older patients (75 years and older) compared to younger patients, with median overall survival of 11.2 months for older patients versus 12.2 months for younger patients.

The safety profile of RAM+DOC was well tolerated in older patients, especially when combined with prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF), suggesting that this treatment approach could be a viable option for older patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer. Sakaguchi, T., Furuya, N., Ito, K., et al.[2023]

In a study of 237 patients with advanced non-small cell lung cancer, the combination of Ramucirumab and Docetaxel showed similar overall survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating that this treatment can be effective across age groups.

However, older patients experienced a higher rate of severe adverse events (56.7% vs. 42.7% in younger patients), suggesting that careful monitoring and potential dose reduction of Docetaxel may enhance safety and improve survival outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study. Matsumoto, K., Tamiya, A., Inagaki, Y., et al.[2023]

In a study of 237 patients with previously treated non-small cell lung cancer (NSCLC), the combination of docetaxel and ramucirumab showed an overall response rate of 25.2% and a disease control rate of 63.9%, with a median progression-free survival of 4.5 months.

The study found that while lung and liver metastases responded well to treatment, patients with poor ECOG performance status (2 or more) and brain metastasis had significantly shorter progression-free survival, indicating that this combination therapy should be used cautiously in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study. Matsumoto, K., Tamiya, A., Matsuda, Y., et al.[2022]

In a study of 237 patients with advanced non-small cell lung cancer (NSCLC), those who received prior immune checkpoint inhibitors (ICI) showed significantly better outcomes when treated with ramucirumab (RAM) and docetaxel (DOC), including higher objective response rates and longer progression-free survival (PFS).

The results suggest that RAM and DOC are more effective when administered after ICI treatment compared to other therapies like cytotoxic agents, bevacizumab, or tyrosine kinase inhibitors, especially in patients who had a favorable tumor response to prior ICI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study. Tanizaki, S., Matsumoto, K., Tamiya, A., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. [2023]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Ramucirumab Plus Docetaxel for Patients with Non-small cell Lung Cancer with Brain Metastases: A Multicenter, Open-Label Single-Arm Phase II Trial. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment. [2023]

5. Singapore pubmed.ncbi.nlm.nih.gov

Extended ICI treatment after first-line chemoimmunotherapy could predict the clinical benefit of ramucirumab plus docetaxel in advanced non-small lung cancer: Post hoc analysis from NEJ051 (REACTIVE study). [2023]

6. 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]

7. Singapore pubmed.ncbi.nlm.nih.gov

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study. [2023]

9. China pubmed.ncbi.nlm.nih.gov

Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study. [2023]