AP160-Complex for Advanced Cancer

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Mayo Clinic

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination in patients with serious cancer. The treatment aims to stop cancer cell growth and boost the immune system to fight the cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any anti-cancer therapy or investigational agents within 4 weeks prior to registration, and you must be off systemic corticosteroids for at least 2 weeks before registration, unless you are on a low dose for chronic conditions. It's best to discuss your specific medications with the trial team.

What data supports the idea that AP160-Complex for Advanced Cancer is an effective drug?

The available research shows that AP160-Complex for Advanced Cancer, also known as nab-paclitaxel, is effective in treating several types of cancer. For instance, it has been shown to improve outcomes in patients with non-small-cell lung cancer (NSCLC) and metastatic breast cancer. In NSCLC, studies have demonstrated that nab-paclitaxel can increase the concentration of the active drug in tumors, which may lead to better treatment results. Additionally, it is approved for use in metastatic breast cancer in both Europe and the US, indicating its recognized effectiveness. Compared to traditional solvent-based paclitaxel, nab-paclitaxel avoids certain toxicities and does not require premedication to prevent infusion-related reactions, making it a safer and more convenient option for patients. ^{1 2 3 4 5}

What safety data is available for nab-paclitaxel?

Nab-paclitaxel, also known as ABI-007, is a solvent-free, albumin-bound formulation of paclitaxel designed to avoid toxicities associated with solvent-based paclitaxel. It has been evaluated in various studies for its safety and efficacy. It is approved for metastatic breast cancer in Europe and the US, and for non-small-cell lung cancer and advanced pancreatic cancer in the US. Studies have shown improved tolerability compared to solvent-based paclitaxel, and trials have determined the maximum-tolerated dose and assessed its pharmacokinetics in different cancer types. ^{1 2 3 5 6}

Is the drug nab-paclitaxel a promising treatment for advanced cancer?

Yes, nab-paclitaxel is a promising drug for advanced cancer. It is a new form of paclitaxel that doesn't use harmful solvents, making it safer and more effective. It has shown better results and fewer side effects in treating breast cancer and is approved for use in other cancers like lung and pancreatic cancer. ^{1 2 3 7 8}

Research Team

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors, including melanoma, who have already tried at least one systemic therapy. Participants must provide consent and a tissue sample for research. There's no limit to prior treatments but the cancer should be non-neurological and without curative options.

Inclusion Criteria

My melanoma cannot be removed with surgery and is stage IV.

Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)

For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment

Exclusion Criteria

I am not willing to use birth control during the study.

I have not fully recovered from my last surgery.

I have had a severe reaction to immune therapy before.

Treatment Details

Interventions

• Nab-paclitaxel (Anti-microtubule Agent)
• STI-3031 (Monoclonal Antibodies)

Trial Overview The trial tests the safety and optimal dose of AP160-complex, a new drug combining chemotherapy (nab-paclitaxel) and immunotherapy (STI-3031). It aims to see if this complex can better halt tumor growth compared to standard therapies in patients with advanced or metastatic solid tumors.

Participant Groups

Group I: Treatment (AP160-complex) Experimental Treatment 5 Interventions

Patients receive AP160-complex IV on study. Patients in the dose-escalation cohort undergo computed tomography/magnetic resonance imaging (MRI) scans, tissue biopsies, and collection of blood samples throughout the trial. Patients in the dose-expansion cohort undergo MRI scan during screening, collection of blood samples during screening and on study, and tissue biopsies throughout the trial.

Nab-paclitaxel is already approved in Canada for the following indications:

Approved in Canada as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

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]

NAB-paclitaxel at a dose of 125 mg/m² was well tolerated in patients with stage IV non-small-cell lung cancer, with no hypersensitivity reactions reported and a maximum-tolerated dose established without significant dose-limiting toxicities.

The treatment showed promising efficacy, with a 30% objective response rate, a median time to progression of 5 months, and a median overall survival of 11 months, indicating its potential as a viable single-agent therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. Rizvi, NA., Riely, GJ., Azzoli, CG., et al.[2015]

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]

ABI-007, a solvent-free albumin-bound paclitaxel, showed significantly higher response rates (33% vs. 19%) and longer time to tumor progression (23.0 weeks vs. 16.9 weeks) compared to standard paclitaxel in a phase III study with 454 patients.

ABI-007 had a lower incidence of severe neutropenia (9% vs. 22%) and did not require premedication, indicating a better safety profile, although it was associated with a higher rate of manageable sensory neuropathy (10% vs. 2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Gradishar, WJ., Tjulandin, S., Davidson, N., et al.[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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

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

Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]

4. 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]

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

Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. [2015]

6. 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]

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

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. [2023]

8. 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]