Chemo-Immunotherapy for Non-Small Cell Lung Cancer

(STAGGER Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Wallace L. Akerley

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of Utah

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of an immune-boosting drug and chemotherapy in adults with advanced lung cancer. The treatment aims to help the immune system fight cancer while also killing cancer cells directly.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking any prohibited medications, a washout period of at least 5 half-lives or as clinically indicated is required before starting the treatment.

What data supports the idea that Chemo-Immunotherapy for Non-Small Cell Lung Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of Chemo-Immunotherapy for Non-Small Cell Lung Cancer. The studies mentioned focus on other treatments and conditions, such as rheumatoid arthritis and a different combination of drugs for lung cancer. Therefore, there is no direct evidence from the provided information to support the effectiveness of Chemo-Immunotherapy for Non-Small Cell Lung Cancer. ^{1 2 3 4 5}

What safety data is available for chemo-immunotherapy in non-small cell lung cancer?

The safety data for the treatment involving Pemetrexed (Alimta) in non-small cell lung cancer (NSCLC) includes reports of scleroderma-like changes in the lower legs, myelosuppression, neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. Pemetrexed is used in combination with platinum compounds like cisplatin and carboplatin, and its safety profile is improved with folic acid and vitamin B12 supplementation. The FDA has approved Pemetrexed in combination with cisplatin for certain cancers, and it is also used in maintenance therapy for NSCLC. Unexpected cumulative toxicity is possible with longer durations of therapy. ^{6 7 8 9 10}

Is the drug combination of Carboplatin, Durvalumab, and Pemetrexed a promising treatment for Non-Small Cell Lung Cancer?

Yes, the combination of these drugs is promising for treating Non-Small Cell Lung Cancer. Pemetrexed, when used with platinum-based drugs like Carboplatin, has shown good results in clinical trials. Adding Durvalumab, which helps the immune system fight cancer, can improve survival rates. This combination has shown potential in improving outcomes for patients. ^{6 11 12 13 14}

Research Team

Wallace L. Akerley

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

Adults with metastatic non-squamous non-small cell lung cancer who haven't had chemoimmunotherapy can join this trial. They must be willing to use effective birth control and follow the study's protocol, including visits and exams. People with certain health conditions or those on immunosuppressive medications (except some steroids) are excluded.

Inclusion Criteria

I am 18 years old or older.

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

I have recovered from side effects of previous treatments, with only mild symptoms remaining.

Exclusion Criteria

You have had an organ transplant from someone else.

I haven't taken immunosuppressive drugs, except allowed steroids, in the last 14 days.

I have not had radiation therapy in the last 2 weeks.

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Durvalumab (Immunotherapy)
• Pemetrexed (Chemotherapy)

Trial Overview The trial is testing two staggered dosing regimens of Durvalumab combined with Pemetrexed and Carboplatin in patients. It aims to determine which regimen is more effective for treating advanced lung cancer in a Phase II open label, randomized setting.

Participant Groups

Group I: Arm B: Immuno-Chemo Experimental Treatment 3 Interventions

ArmB receives immunotherapy on D1 and chemotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Group II: Arm A: Chemo-Immuno Experimental Treatment 3 Interventions

ArmA receives chemotherapy on D1 and immunotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Jeffrey Wilkins

University of Utah

Chief Medical Officer since 2022

MD from Meharry Medical College

Stephen Tullman

University of Utah

Chief Executive Officer since 2022

BS in Accounting from Rutgers University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

A systematic review of phase 3 clinical trials involving biologic DMARDs (Adalimumab, Baricitinib, Pefacitinib, and Sirukumab) showed significant improvements in the ACR 20 response rate for these newer agents, with rates of 72.4% for SB5, 70% for Baricitinib, and up to 74.5% for Pefacitinib at various time points.

The study indicates that these newer biologics not only improve rheumatoid arthritis symptoms effectively but also maintain an acceptable safety profile compared to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review. Zago, BA., Priyadharshini, A., Vijayakumar, TM.[2022]

In the BREVACTA study involving 656 patients with rheumatoid arthritis, subcutaneous tocilizumab (TCZ-SC) demonstrated significantly greater efficacy than placebo, achieving an ACR20 response in 60.9% of patients compared to 31.5% for placebo after 24 weeks.

TCZ-SC was well tolerated, with a safety profile comparable to previous studies, showing similar rates of adverse events and serious adverse events between TCZ-SC and placebo, although injection site reactions were more common with TCZ-SC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Kivitz, A., Olech, E., Borofsky, M., et al.[2022]

Methotrexate (MTX) is the preferred treatment for rheumatoid arthritis due to its favorable safety profile and cost-effectiveness, with an optimal starting dose of 15 mg/week that can be increased to 25-30 mg/week based on patient tolerance.

While oral MTX is commonly used, subcutaneous administration may offer better efficacy and patient compliance, as it has been associated with fewer disease exacerbations and improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methotrexate in rheumatoid arthritis: optimizing therapy among different formulations. Current and emerging paradigms. Cipriani, P., Ruscitti, P., Carubbi, F., et al.[2018]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

Pemetrexed, a treatment for malignant pleural mesothelioma and non-small cell lung cancer, has been associated with a new toxicity resembling scleroderma, as seen in two cases involving painful induration and edema of the lower extremities.

This adverse effect can be mistaken for erysipelas due to similar symptoms, but it lacks fever; recognizing this toxicity is crucial for timely diagnosis and management, and folate and vitamin B12 supplementation may help reduce its incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pemetrexed-induced scleroderma-like changes in the lower legs]. Corbaux, C., Marie, J., Meraud, JP., et al.[2015]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

Pemetrexed, when combined with carboplatin, has shown promising antitumor activity with mild toxicity in phase II clinical trials, but it can lead to serious adverse reactions such as toxic epidermal necrolysis, as seen in a reported case.

Supplementation with folic acid and vitamin B12 is recommended during pemetrexed treatment to help reduce the risk of hematological and gastrointestinal side effects, although severe skin reactions can still occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Bosch-Barrera, J., Gaztañaga, M., Ceballos, J., et al.[2015]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Phase II study on Javanica oil emulsion injection (Yadanzi®) combined with chemotherapy in treating patients with advanced lung adenocarcinoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tofacitinib and peficitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. [2021]

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

Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review. [2022]

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

Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. [2022]

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

Methotrexate in rheumatoid arthritis: optimizing therapy among different formulations. Current and emerging paradigms. [2018]

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

Review of a promising new agent--pemetrexed disodium. [2022]

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

FDA drug approval summaries: pemetrexed (Alimta). [2022]

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

Pemetrexed and communicating hydrocephalus. [2021]

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

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. [2015]

10. France pubmed.ncbi.nlm.nih.gov

[Pemetrexed-induced scleroderma-like changes in the lower legs]. [2015]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

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

Physical and chemical stability of pemetrexed solutions in plastic syringes. [2015]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. [2015]

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

Physical and chemical stability of pemetrexed in infusion solutions. [2022]