Tumor Treating Fields + Chemotherapy for Cancer

Overseen By Apostolia M Tsimberidou

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Cabozantinib, Nab-paclitaxel, Atezolizumab

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Active brain metastasis, Cardiac conditions, Uncontrolled diabetes, Severe infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 21-28 days per cycle, repeated

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment method for individuals with advanced cancers in the abdomen or chest that have spread elsewhere. It combines wearable devices called tumor treating fields, which use electrical fields to slow tumor growth, with various cancer drugs, including Atezolizumab (Tecentriq), Cabozantinib (Cabometyx), and Nab-paclitaxel (Abraxane). The trial seeks to determine the safest and most effective dose of this combined treatment. It is suitable for those whose cancer has not responded to standard treatments and who can operate the device or have assistance. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have had anticancer therapy or radiation therapy within 2 weeks before starting the trial. If you are already on cabozantinib and have progressive disease, you can continue with it while participating in the trial.

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

Research has shown that Tumor Treating Fields (TTFields) therapy is generally safe for various cancers, including pancreatic and liver cancers. This treatment uses electrical fields to inhibit cancer cell growth. Studies have found it to be safe, with no unexpected issues.

Cabozantinib, a kinase inhibitor, is approved for some advanced cancers. Its safety is well-documented, and recent studies have not identified any new safety concerns.

When combined with atezolizumab (an immunotherapy) and nab-paclitaxel (a chemotherapy), studies have shown that TTFields is safe for other cancers. These treatments have been tested together in various ways, and their safety aligns with past research.

This trial is in an early phase, focusing on safety, so understanding how well these treatments are tolerated remains a priority. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Tumor Treating Fields (TTF) offer a unique approach by using alternating electric fields to disrupt cancer cell division, which is different from traditional chemotherapy that targets rapidly dividing cells through chemical means. In Cohort 1, cabozantinib is combined with TTF, offering a novel angle by inhibiting cancer growth and spread via the MET and VEGFR pathways. Cohort 2 is distinctive for combining TTF with atezolizumab, an immunotherapy that boosts the body's immune response against cancer, and nab-paclitaxel, a chemotherapy that enhances drug delivery into tumors. This combination strives to tackle cancer from multiple fronts, potentially improving effectiveness and offering new hope for patients.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research shows that Tumor Treating Fields (TTFields) can extend the lives of patients with certain cancers, with some studies reporting survival times of up to 19.6 months. This treatment uses electrical fields to stop cancer cells from dividing. In this trial, participants in Cohort 1 will receive TTFields combined with Cabozantinib, which has slowed cancer growth by 34% and shrunk tumors in 33% of cases, making it a promising option. Participants in Cohort 2 will receive TTFields along with Atezolizumab and Nab-paclitaxel. Atezolizumab, an immunotherapy, has improved survival rates; one study showed patients lived a median of 19.2 months. Nab-paclitaxel, a chemotherapy drug, has reduced cancer progression by 31% when combined with other treatments. This trial tests these treatments together to determine if they work even better against advanced solid tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Apostolia M. Tsimberidou

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors in the abdomen or thorax, who are physically able to handle treatment (ECOG 0-1), have a life expectancy over 3 months, and meet certain blood count criteria. They must not be pregnant/breastfeeding, agree to use contraception, and should not have severe medical conditions or allergies that conflict with the treatments.

Inclusion Criteria

I am fully active or can carry out light work.

Life expectancy >3 months

Contraception required for women of childbearing potential

Exclusion Criteria

Allergy or hypersensitivity to specific medications or materials

Pregnancy or breastfeeding

Implanted pacemaker, defibrillator or other electrical medical devices

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tumor Treating Fields (TTF) therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab. Cohort 1: TTF and cabozantinib for 21-day cycles. Cohort 2: TTF, nab-paclitaxel, and atezolizumab for 28-day cycles.

21-28 days per cycle, repeated

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cabozantinib
• Nab-paclitaxel
• Tumor Treating Fields (TTF)

Trial Overview The trial tests Tumor Treating Fields Therapy using NovoTTF devices combined with cabozantinib or nab-paclitaxel plus atezolizumab. It aims to find safe doses and see how well these combinations control cancer by disrupting cell division, blocking tumor growth signals, killing cancer cells directly, and boosting immune responses against cancer.

How Is the Trial Designed?

Group I: Cohort 2 (TFF, atezolizumab, nab-paclitaxel) Experimental Treatment 3 Interventions

Patients receive TTF continuously for at least 18 hours per day on days 1-28 of each cycle. Patients also receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 of each cycle and atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Cohort 1 (TTF, cabozantinib) Experimental Treatment 2 Interventions

Patients receive TTF continuously for at least 18 hours per day on days 1-21 of each cycle. Patients also receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

ABI-007, a novel nanoparticle formulation of paclitaxel, demonstrated a significant overall response rate of 48% in treating metastatic breast cancer, with even higher rates of 64% for first-line therapy, indicating its efficacy in this patient population.

The treatment was well-tolerated, with no severe hypersensitivity reactions reported despite the absence of premedication, and typical toxicities associated with paclitaxel, such as neutropenia and sensory neuropathy, were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. Ibrahim, NK., Samuels, B., Page, R., et al.[2022]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

ABI-007, a novel formulation of paclitaxel, can be safely administered at higher doses than traditional paclitaxel formulations, with maximum-tolerated doses of 100 mg/m² for heavily pretreated patients and 150 mg/m² for lightly pretreated patients.

The study showed partial antitumor responses in patients with breast, lung, and ovarian cancers, indicating that ABI-007 may be effective even in those previously treated with standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Nyman, DW., Campbell, KJ., Hersh, E., et al.[2022]

In a phase 3 trial involving 902 patients with untreated metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel significantly improved progression-free survival compared to nab-paclitaxel alone, with median survival times of 7.2 months versus 5.5 months, respectively.

The combination therapy also showed promising overall survival results, particularly in patients with PD-L1-positive tumors, where median overall survival was 25.0 months for the combination versus 15.5 months for the placebo group, indicating enhanced efficacy without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Schmid, P., Adams, S., Rugo, HS., et al.[2021]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

Citations

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IMpower110 Clinical Trial Results - TECENTRIQ-HCP.com 41% reduction in the risk of death vs chemotherapy · Median PFS was 8.1 months with TECENTRIQ (95% CI, 6.8, 11.0) vs 5.0 months with platinum-based chemotherapy ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

3. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab. Patients who received TECENTRIQ with chemotherapy† had a 30% reduced ...

4. tecentriq.com tecentriq.com/metastatic-nsclc/results/how-tecentriq-may-help.html

Effectiveness & Safety of TECENTRIQ® (atezolizumab) for ... Median overall survival (OS) was 19.2 months for patients taking TECENTRIQ® (atezolizumab. Median OS=the length of time from the start of treatment in a ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9716834/

updated long-term efficacy of atezolizumab in a diverse ... In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety.

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A review of tumor treating fields (TTFields) Its purpose is to inhibit cancer cell proliferation and induce cell death. Despite promising outcomes from clinical trials, TTFields have received FDA approval ...

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-results-subgroup-analysis-cabinet-phase-3

Press Release - Exelixis CABOMETYX reduced the risk of disease progression or death by 81% versus placebo in patients with advanced lung or thymic neuroendocrine ...

8. cancertherapyadvisor.com cancertherapyadvisor.com/news/cabometyx-approved-for-advanced-neuroendocrine-tumors/

Cabometyx Approved for Advanced Neuroendocrine Tumors The safety profile of cabozantinib was consistent with findings reported in prior clinical trials. No new safety signals were identified.

9. cco.amegroups.org cco.amegroups.org/article/view/118769/html

Tumor treating fields: narrative review of a promising treatment ... Moreover, TTFields therapy has exhibited promising safety profiles across a diverse range of cancers including pancreatic cancer, hepatocellular carcinoma (HCC) ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT03940196

NCT03940196 | Effect of Tumor Treating Fields (TTFields, ... The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields (TTFields) concomitant with ...