Chemotherapy + Radiation +/− Metformin for Lung Cancer

No longer recruiting at 229 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must not be taking: Metformin, Insulin

Disqualifiers: Diabetes, Metastasis, Kidney disease, 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: Unknown

Duration: Concurrent chemoradiotherapy phase followed by consolidation therapy

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding metformin hydrochloride to chemotherapy and radiation therapy enhances treatment effectiveness for people with stage III non-small cell lung cancer. Chemotherapy uses drugs like carboplatin and paclitaxel to kill or inhibit the growth of cancer cells, while radiation therapy employs high-energy x-rays to shrink tumors. Researchers are testing metformin, a medication commonly used for type 2 diabetes, to see if it can help reduce tumor size and prevent recurrence. People with stage III non-small cell lung cancer who cannot or choose not to undergo surgery may be suitable for this trial. As a Phase 2 trial, this study focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients currently using metformin, other oral diabetes medications, or insulin. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metformin, when combined with chemotherapy and radiation, might be safe and could benefit people with lung cancer. Some studies suggest that metformin can extend the lives of lung cancer patients. This implies that patients may have a longer life expectancy when taking metformin alongside their cancer treatments.

In certain studies, patients took metformin for about 19 months on average, indicating it is generally well-tolerated over this period. Reports also highlight metformin's benefits for people with diabetes who have cancer, supporting its potential safety.

Overall, while researchers continue to study metformin, the evidence so far indicates it might be safe and helpful when added to cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lung cancer, which typically include chemotherapy and radiation, the addition of metformin is what makes this approach unique. Metformin, commonly known as a diabetes medication, is being tested for its potential to enhance the effectiveness of chemoradiation. Researchers are excited because metformin might improve cancer cell sensitivity to radiation and chemotherapy, possibly leading to better outcomes for patients. This combination could offer a new way to boost the effectiveness of existing treatments and improve patient survival rates.

What evidence suggests that this trial's treatments could be effective for stage III non-small cell lung cancer?

Research has shown that combining metformin with chemotherapy and radiation might enhance lung cancer treatment. In animal studies, metformin helped shrink tumors and increased survival rates. For people with lung cancer, one study found that metformin improved survival rates by 25%. Metformin also enhances the effectiveness of radiation therapy by making cancer cells more sensitive to treatment. In this trial, some participants will receive the standard treatment of chemotherapy and radiation, while others will receive metformin in addition, which could offer extra benefits for some patients. ^{4 5 6 7 8}

Who Is on the Research Team?

Theodoros Tsakiridis

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage III non-small cell lung cancer who have good organ function and no history of allergic reactions to certain chemotherapy drugs. They must not have had previous systemic chemotherapy or radiotherapy overlapping the study area, no distant metastasis, and cannot be using metformin or other diabetes medications.

Inclusion Criteria

My recent blood test shows my bone marrow is working well.

It has been over 3 weeks since my chest surgery.

Patients must have a disease that can be measured.

Exclusion Criteria

Severe, active co-morbidity, defined as follows

I am allergic to paclitaxel, other taxanes, or carboplatin.

My lung cancer is a mix of small cell and non-small cell types.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemoradiotherapy with or without metformin hydrochloride

Concurrent chemoradiotherapy phase followed by consolidation therapy

Regular visits for chemotherapy and radiation sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks initially, then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter

Multiple follow-up visits over several years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Metformin Hydrochloride
• Paclitaxel
• Radiation Therapy

Trial Overview The trial is testing if adding metformin hydrochloride to standard chemotherapy (carboplatin and paclitaxel) and radiation therapy improves outcomes in treating stage III non-small cell lung cancer. It's a phase II study where patients are randomly assigned to receive either the standard treatment alone or with metformin.

How Is the Trial Designed?

Group I: Metformin + Chemoradiation Experimental Treatment 4 Interventions

Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin

Group II: Chemoradiation Active Control 3 Interventions

60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin

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?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9685221/

Research progress on the therapeutic effect and mechanism ... In mice with lung cancer, 250 mg/kg/day metformin reduced tumor volume, increased survival rate and decreased YAP expression level in transplanted tumors (94).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12455790/

Are metformin-based combination approaches beneficial for ... To that end, repurposed drugs such as metformin have been evaluated against many cancer types, including NSCLC. Metformin, a widely used oral ...

3. elsevier.es elsevier.es/es-revista-medicina-clinica-english-edition--462-articulo-metformin-improves-survival-in-lung-S2387020619301093?covid=Dr56DrLjUdaMjzAgze452SzSInMN&rfr=truhgiz&y=kEzTXsahn8atJufRpNPuIGh67s1

Metformin improves survival in lung cancer patients with ... In the pooled analysis, we found that metformin treatment significantly improved the survival of lung cancer patients (hazard ratio=0.75, 95% confidence ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1043661824003128

Metformin: From diabetes to cancer to prolongation of life Metformin use has been shown to reduce the frequency of specific cancers, in particular breast cancer [141] and to be an effective radiosensitizer in the ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/lmt-2018-0016

Clinical Outcomes in Non-Small-Cell Lung Cancer Patients ... Overall, the median duration of metformin therapy was 18.8 months. The median duration that patients received metformin and ICI concurrently was 2.3 months.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4200668/

Metformin in cancer prevention and therapy - PMC The results of numerous preclinical, epidemiological and clinical studies suggested that metformin use is associated with inhibition of cancer cell growth and ...

7. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct04931017

Metformin for Chemoprevention of Lung Cancer in Overweight ... Metformin use has been associated with improved survival in patients with non-small cell lung carcinoma, a specific type of lung cancer, and it has also been ...

8. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04263-8

Metformin and cancer hallmarks: shedding new lights on ... Epidemiological studies have revealed that metformin exerts protective effects on people with diabetes suffering from cancer [10,11,12].