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

Trial Summary

What is the purpose of this trial?

This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.

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.

What data supports the effectiveness of the drug nanoparticle albumin-bound paclitaxel (Abraxane) in cancer treatment?

Research shows that nanoparticle albumin-bound paclitaxel (Abraxane) can improve the effectiveness and safety of cancer treatment compared to traditional formulations. It has been associated with better response rates and longer survival in breast cancer and has shown promise in treating lung cancer and peritoneal metastases. ^{1 2 3 4 5}

Is the treatment with nanoparticle albumin-bound paclitaxel (Abraxane) generally safe for humans?

Research shows that nanoparticle albumin-bound paclitaxel (Abraxane) is generally well tolerated and safer than traditional formulations because it avoids using toxic solvents. It has been associated with improved safety and tolerability in patients with breast cancer. ^{3 4 5 6 7}

What makes the drug combination of Atezolizumab, Cabozantinib, and Nab-paclitaxel unique for cancer treatment?

This drug combination is unique because Nab-paclitaxel (Abraxane) is a special form of paclitaxel that uses nanoparticles to deliver the drug more effectively to tumors, avoiding the toxic solvents used in traditional formulations. This can lead to better outcomes and fewer side effects. Additionally, combining it with Atezolizumab, an immune therapy, may enhance its anticancer activity, especially in aggressive cancers like triple-negative breast cancer. ^{1 3 5 6 7}

Research Team

Apostolia M. Tsimberidou

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

My bone marrow is functioning normally.

Life expectancy >3 months

Exclusion Criteria

Allergy or hypersensitivity to specific medications or materials

Pregnancy or breastfeeding

Implanted pacemaker, defibrillator or other electrical medical devices

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. [2023]

2. England 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. [2022]

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

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

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

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. [2021]

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

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. [2022]

7. United States 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. [2022]