Tumor Treating Fields for Non-Small Cell Lung Cancer

(NOVOCURE Trial)

Overseen By Matthew Gumbleton, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Utah

Must not be taking: Immunosuppressants

Disqualifiers: Prior radiation, Cardiovascular disorders, Autoimmune disorders, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of Tumor Treating Fields (TTFields) alongside standard treatments for non-small cell lung cancer that cannot be surgically removed. Researchers aim to determine if adding TTFields to regular chemoradiation and the follow-up drug durvalumab (an immunotherapy drug) causes any serious side effects. The trial seeks participants with stage III non-small cell lung cancer, particularly those diagnosed with this specific type who can use the TTFields system. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that a washout period (time without taking certain medications) of at least five half-lives is required for prohibited medications before starting treatment. It's best to discuss your specific medications with the trial team.

What prior data suggests that the NovoTTF-200T (TTFields) System is safe for use in non-small cell lung cancer?

Research shows that Tumor Treating Fields (TTFields) are generally well-tolerated by people with non-small cell lung cancer (NSCLC). Previous studies have shown that TTFields do not cause side effects affecting the whole body. This device uses electric fields to target cancer cells and is designed to be safe when combined with other treatments.

The FDA approved a similar device, Optune Lua, for adults with advanced NSCLC, suggesting its safety. This approval provides reassurance about the safety of TTFields, although every treatment can have risks. Participants in past studies generally did well without serious safety concerns.

Since this is an early-phase trial, the main goal is to identify any serious side effects that might halt the treatment. Safety is being closely monitored. However, existing data supports TTFields as a promising option without major safety issues reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tumor Treating Fields (TTF) for non-small cell lung cancer because it offers a novel approach by using electric fields to disrupt cancer cell division. Unlike traditional treatments like chemotherapy and radiation that target rapidly dividing cells generally, TTF specifically targets the mitotic process, potentially reducing damage to healthy cells. This method could lead to fewer side effects and improved quality of life for patients. Additionally, TTF can be used alongside existing therapies such as durvalumab, potentially enhancing overall treatment efficacy.

What evidence suggests that the NovoTTF-200T System is effective for non-small cell lung cancer?

Research has shown that Tumor Treating Fields (TTFields) can extend the lives of people with non-small cell lung cancer (NSCLC). One study found that TTFields significantly increased the overall survival of NSCLC patients. This therapy uses electric fields to disrupt cancer cell division, helping to stop tumor growth. Another study found that TTFields can enhance the effectiveness of chemotherapy, improving treatment outcomes. The FDA has approved TTFields for treating metastatic NSCLC, recognizing its effectiveness. In this trial, participants will receive TTFields therapy for varying durations to assess its impact when combined with standard care treatments, highlighting the potential benefits for NSCLC patients. ^{1 3 4 5 6}

Who Is on the Research Team?

Matthew Gumbleton, MD, PhD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for adults with stage IIIA or IIIB non-small cell lung cancer (NSCLC) that can't be removed by surgery. Participants should have recovered from any previous radiation-induced pneumonitis, be able to use the NovoTTF-200T System independently or with help, and meet specific health criteria including organ function. Pregnant individuals or those not recovered from prior cancer therapies are excluded.

Inclusion Criteria

Resolution of any pneumonitis from prior radiation therapy to < grade 1 per the treating investigator

Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)

Clinical AJCC (AJCC, 8th ed.) stage IIIA or IIIB NSCLC with unresectable disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Chemoradiation with TTFields

Participants receive standard of care concurrent chemoradiation and treatment with TTFields

12 weeks

Consolidation Durvalumab with TTFields

Participants receive consolidation therapy with durvalumab and TTFields

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Durvalumab
• NovoTTF-200T (TTFields) System

Trial Overview The study tests the safety of Tumor Treating Fields (TTFields) combined with standard chemoradiation and durvalumab in NSCLC patients. It has two steps: first, TTFields with chemoradiation; second, adding durvalumab post-chemoradiation. The main focus is on dose-limiting toxicities during treatment.

How Is the Trial Designed?

Group I: Device Duration Level 2 Experimental Treatment 3 Interventions

Participants in in Device Duration Level 2 will begin TTF therapy during SOC durvalumab and SOC Concurrent chemoradiation following Device Duration Level 1.

Group II: Device Duration Level 1 Experimental Treatment 2 Interventions

Participants in Device Duration Level 1 will receive Tumor Treatment Fields (TTF) therapy during standard of care consolidation durvalumab.

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?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

In a phase II study involving 46 adults with refractory and relapsed acute leukemia, carboplatin administered via continuous infusion led to a 17% complete remission rate, indicating its effectiveness as a treatment option for this patient population.

While carboplatin showed some nonhematologic toxicity, such as mild gastrointestinal issues and manageable ototoxicity, the major concern was prolonged myelosuppression, with infections being the leading cause of death among participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose carboplatin in the treatment of hematologic malignancies. Vogler, WR.[2018]

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]

Carboplatin alone demonstrated a 20% response rate in previously untreated patients with advanced non-small cell lung cancer (NSCLC), indicating its effectiveness as a single-agent treatment.

The combination of carboplatin and etoposide showed a higher response rate of 26.7%, but it also resulted in significantly greater myelosuppressive toxicity, suggesting that while the combination is effective, it may come with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II studies with carboplatin in non-small cell lung cancer. Gatzemeier, U., Heckmayr, M., Neuhauss, R., et al.[2018]

Carboplatin, a platinum-based chemotherapy, is less toxic than cisplatin and can be administered in an outpatient setting, making it a safer option for non-small cell lung cancer patients.

The combination of gemcitabine and carboplatin has been shown to be effective, well-tolerated, and potentially more cost-effective compared to other third-generation chemotherapy combinations, contributing to improved survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin: is this the best combination for non-small cell lung cancer? Saha, A., Rudd, R.[2022]

In a multicenter phase II trial involving 129 patients with bronchogenic carcinoma, carboplatin showed an overall response rate of 17.8%, with a notably higher response rate of 28.4% in patients with small-cell lung cancer.

The treatment was associated with significant toxic effects, particularly thrombocytopenia and leukopenia, affecting nearly half of the patients, but it did not result in renal, aural, or neurotoxicities, indicating a relatively safe profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in patients with nonresected lung cancer. Japan Cooperative Oncology Group on Lung Cancer. [2019]

In a study of 70 patients with inoperable non-small cell lung cancer (NSCLC), carboplatin alone showed a 16% overall response rate with an acceptable safety profile, indicating its potential as a treatment option.

Combination therapies involving carboplatin with other drugs like etoposide and vinblastine yielded response rates of 11%, 12%, and 20%, respectively, but with increased toxicity, particularly myelosuppression, highlighting the need to balance efficacy and safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. Green, MR., Kreisman, H., Doll, DC., et al.[2018]

In a study of 83 patients with advanced non-small cell lung cancer, a carboplatin and gemcitabine regimen resulted in a 43.4% overall response rate, indicating its effectiveness as a treatment option.

The regimen was well-tolerated across different age groups, with similar rates of severe side effects (grade 3-4 toxicity) in both elderly and non-elderly patients, suggesting it is a safe option for older patients as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin treatment in advanced NSCLC: a retrospective evaluation including elderly patients. Murialdo, R., Boy, D., Bertolotti, F., et al.[2022]

Carboplatin is a less toxic alternative to cisplatin, allowing for comparable antitumor doses with reduced side effects, particularly in terms of nephrotoxicity and severity of nausea and vomiting.

In phase I studies involving various adult and pediatric cancers, carboplatin showed objective responses while primarily causing reversible myelosuppression, with recommended dosing strategies established for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. Foster, BJ., Clagett-Carr, K., Leyland-Jones, B., et al.[2019]

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 meta-analysis of 486 patients with advanced non-squamous non-small cell lung cancer, the pemetrexed plus carboplatin regimen at 5 mg/min•mL (PCb5) showed a significantly lower incidence of treatment-emergent adverse events (TEAEs) compared to the 6 mg/min•mL (PCb6) regimen, including less thrombocytopenia, anemia, and fatigue.

Despite the differences in safety profiles, both PCb5 and PCb6 regimens demonstrated similar efficacy outcomes in terms of overall survival and progression-free survival, indicating that PCb5 may be a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. Okamoto, I., Schuette, WH., Stinchcombe, TE., et al.[2018]

Carboplatin is a safer alternative to cisplatin for treating small cell lung cancer (SCLC) due to its lower risk of renal, neuro, and ototoxicity, and shows similar effectiveness in combination regimens, although more randomized trials are needed to confirm this.

In non-small cell lung cancer (NSCLC), carboplatin has an overall response rate of nearly 10% and can be as effective as other treatment combinations, making it a suitable option for patients with existing health issues related to kidney or nerve function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of therapeutic trials of carboplatin in lung cancer. Bunn, PA.[2018]

Citations

1. novocuretrials.com novocuretrials.com/cancer-clinical-trials/non-small-cell-lung-cancer-clinical-trial-lunar

LUNAR - NSCLC Clinical Trial Update: The LUNAR study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival over ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11807771/

Estimating the Cost-Effectiveness of Tumor Treating Fields ... For TTFields therapy plus docetaxel, the life-year gain was 0.23 and the QALY gain was 0.17, with an ICER of $306,029 per QALY gained.

3. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf23/P230042C.pdf

Optune LuaTM for Non-Small Cell Lung Cancer (NSCLC) ... Optune Lua for NSCLC delivers TTFields at 150 kHz to the entire chest cavity. The device's treatment parameters are preset by Novocure. No adjustments can be ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02973789

Study Details: Tumor Treating Fields for NSCLC Stage 4 Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

5. novocure.com novocure.com/fda-approves-novocures-optune-lua-for-the-treatment-of-metastatic-non-small-cell-lung-cancer

FDA Approves Novocure's Optune Lua® for the Treatment ... It is indicated for adult patients with metastatic non-small cell lung cancer (mNSCLC) who have progressed on or after a platinum-based regimen.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf23/P230042b.pdf

Tumor Treatment Fields II. Device Tr - accessdata.fda.gov Optune Lua concurrent with PD-1/PD-L1 inhibitors or docetaxel is indicated for adult patients with metastatic non-small cell lung cancer who ...