Tumor Treating Fields for Non-Small Cell Lung Cancer

(NOVOCURE Trial)

Overseen By Wallace Akerley, MD

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

Trial Summary

What is the purpose of this trial?

The goal of this open-label, Phase 1 clinical trial is to determine the safety of TTFields started concurrently with SOC chemoradiation and during consolidation durvalumab in locally advanced, unresectable stage III non-small cell lung cancer (NSCLC). The main question it aims to answer is, "What is the rate of dose-limiting toxicities (DLTs) with TTFields in addition to concurrent chemoradiation and consolidation durvalumab?" Step 1 * All participants will be screened and enrolled in Step 1 prior to SOC concurrent chemoradiation. * The purpose of the Step 1 Registration is to ensure that eligible participants are candidate for concurrent chemoradiation and do not have contraindications to TTF therapy or immunotherapy. * Starting Level: Participants in Device Duration Level 1 will receive standard of care concurrent chemoradiation following Step 1 Registration. * Escalation Level : Participants in Device Duration Level 2 will begin standard of care chemoradiation and treatment with TTFields following Step 1 Registration. Step 2 * All participants will complete Step 2 screening and enrollment prior to receiving treatment with durvalumab consolidation therapy and TTFields. * The purpose of the Step 2 registration is to ensure that eligible patients meet criteria for consolidation durvalumab after completion of CRT and do not have contraindications to TTF. therapy or immunotherapy.

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 data supports the effectiveness of the treatment for non-small cell lung cancer?

Carboplatin, a key component of the treatment, has shown effectiveness in non-small cell lung cancer (NSCLC) with response rates ranging from 10% to 20% when used alone or in combination with other drugs. Additionally, the combination of paclitaxel and carboplatin has demonstrated promising results, with 1-year survival rates as high as 54% in patients with advanced NSCLC. ^{1 2 3 4 5}

Is Tumor Treating Fields (TTFields) safe for humans?

Carboplatin, a component of Tumor Treating Fields, has been studied in various trials and is generally considered safe, though it can cause side effects like low blood cell counts, nausea, and mild kidney issues. Serious side effects are rare, and the treatment is less toxic than similar drugs like cisplatin. ^{5 6 7 8 9}

How is the Tumor Treating Fields and Carboplatin treatment different for non-small cell lung cancer?

The Tumor Treating Fields treatment is unique because it uses electric fields to disrupt cancer cell division, which is different from traditional chemotherapy drugs like carboplatin that target cancer cells chemically. This approach offers a novel mechanism of action compared to standard chemotherapy options. ^{2 4 5 10 11}

Research Team

Wallace L. Akerley

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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]

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]

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]

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 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]

References

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

Phase II studies with carboplatin in non-small cell lung cancer. [2018]

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

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

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

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

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

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. [2018]

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

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

7. England 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. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. [2019]

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

Gemcitabine and carboplatin: is this the best combination for non-small cell lung cancer? [2022]

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

Gemcitabine and carboplatin treatment in advanced NSCLC: a retrospective evaluation including elderly patients. [2022]