Serabelisib + Diet/Nab-paclitaxel for Solid Cancers

Recruiting at 19 trial locations

Overseen By Study Inquiry

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Faeth Therapeutics

Must not be taking: PI3K inhibitors, Insulin, Antacids, others

Disqualifiers: Brain tumor, Diabetes, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new cancer drug called serabelisib with a special diet that lowers insulin levels, and sometimes with another drug called nab-paclitaxel. nab-Paclitaxel is used for treating triple-negative breast cancer. It targets cancer patients who suffer from severe side effects of current treatments. The goal is to block cancer growth pathways and lower insulin to reduce side effects and improve treatment effectiveness.

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

The trial protocol does not specify if you need to stop your current medications, but it does mention that you should not take certain medications like strong CYP3A4 inducers/inhibitors, histamine-H2 receptor antagonists, PPIs, and neutralizing antacids close to the start of the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Serabelisib + Diet/Nab-paclitaxel for solid cancers?

Research shows that nab-paclitaxel, a component of the treatment, improves survival in patients with metastatic pancreatic cancer and enhances drug distribution and tumor penetration compared to other forms of paclitaxel. Additionally, nab-paclitaxel has shown effectiveness in treating advanced non-small cell lung cancer and metastatic breast cancer. ^{1 2 3 4 5}

Is the combination of Serabelisib and nab-paclitaxel safe for humans?

Studies have shown that nab-paclitaxel, when combined with other drugs like gemcitabine, is generally safe for treating various cancers, including pancreatic and gastric cancer. The combination of Serabelisib with paclitaxel has been evaluated for safety in patients with advanced solid tumors, indicating it is generally safe for human use. ^{1 6 7 8 9}

What makes the drug Serabelisib + Diet/Nab-paclitaxel unique for treating solid cancers?

Serabelisib is unique because it targets specific pathways in cancer cells, potentially enhancing the effectiveness of nab-paclitaxel, which is a form of paclitaxel that is bound to albumin to improve delivery to tumors and reduce side effects. This combination aims to improve treatment outcomes by using a novel mechanism of action and a more efficient drug delivery system. ^{1 2 6 10 11}

Research Team

Vicky Makker

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced solid tumors harboring PIK3CA mutations, who have tried and failed or were intolerant to a limited number of previous treatments. They must be able to consent, have a life expectancy over 3 months, adequate organ function, and no severe comorbidities. Women must not be pregnant and agree to use birth control; men must also agree to contraception.

Inclusion Criteria

I have had 3 or fewer chemotherapy treatments for ovarian cancer.

I have colorectal cancer and have had 2 or fewer treatments for it since it spread.

My cancer has come back and was confirmed by a lab test.

Exclusion Criteria

I have been treated with a PI3K inhibitor.

I had chemotherapy or radiation less than 3 weeks ago and still have significant side effects.

I have severe gout that isn't controlled by treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive serabelisib in combination with an Insulin Suppressing Diet, with or without nab-paclitaxel, for up to 12 months

12 months

Weekly visits for nab-paclitaxel administration (if applicable)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

Treatment Details

Interventions

• Insulin Suppressing Diet
• Nab-paclitaxel
• Serabelisib

Trial Overview The trial is testing the combination of Serabelisib (a PI3K inhibitor) with an Insulin Suppressing Diet (ISD), both alone and alongside Nab-paclitaxel chemotherapy. The goal is to improve safety, reduce side effects, and enhance cancer-fighting efficacy in patients with specific genetic tumor profiles.

Participant Groups

Group I: Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma Experimental Treatment 3 Interventions

Subjects will receive dose of serabelisib as determined from Cohorts 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.

Group II: Cohort 3 - Expansion Endometrial Cancer Experimental Treatment 3 Interventions

Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.

Group III: Cohort 2 - Expansion Colorectal Cancer Experimental Treatment 2 Interventions

Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months

Group IV: Cohort 1b - Dose Modification with Nab-Paclitaxel Experimental Treatment 3 Interventions

Subjects with endometrial cancer, ovarian clear cell or ovarian endometriod carcinoma will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months. In addition, these subjects will receive nab-paclitaxel intravenously weekly.

Group V: Cohort 1a - Dose Modification without nab-paclitaxel Experimental Treatment 2 Interventions

Subjects with any solid tumor will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months

Who Is Running the Clinical Trial?

Faeth Therapeutics

Lead Sponsor

Trials

4

Recruited

170+

Findings from Research

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

In a study of 102 heavily pre-treated metastatic breast cancer patients, nab-paclitaxel demonstrated an objective response rate of 22.9% and a median overall survival of 8.7 months, indicating its efficacy as a treatment option.

Patients receiving a weekly regimen of nab-paclitaxel experienced significantly longer progression-free survival (5.5 months) compared to those on a 3-weekly regimen (2.3 months), highlighting the importance of treatment scheduling in optimizing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer. Kim, JS., Suh, KJ., Lee, DW., et al.[2022]

The combination of sapanisertib, serabelisib, and paclitaxel was found to be safe and well tolerated in a Phase I trial involving 19 patients with advanced solid tumors, with manageable adverse effects such as decreased white blood cells and anemia.

Preliminary efficacy results were promising, showing an overall response rate of 47% and a clinical benefit rate of 73%, particularly in patients with specific genetic abnormalities, indicating potential effectiveness in a challenging treatment population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors. Starks, DC., Rojas-Espaillat, L., Meissner, T., et al.[2022]

In a phase I/II study involving 34 Japanese patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine demonstrated a high objective response rate of 58.8%, indicating promising efficacy for this treatment regimen.

The treatment was associated with manageable safety, with the most common severe adverse effects being neutropenia (70.6%) and leukopenia (55.9%), but no treatment-related deaths were reported, suggesting that the regimen can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Ueno, H., Ikeda, M., Ueno, M., 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]

In a study involving 64 pediatric patients with recurrent or refractory solid tumors, nab-Paclitaxel was found to have a tolerable safety profile, with the maximum tolerated dose (MTD) not reached, but 240 mg/m2 was selected as the recommended phase II dose due to its pharmacokinetics and antitumor activity.

Efficacy results showed that at doses of 210 mg/m2 and above, there were complete and partial responses in a small percentage of patients, with 22% achieving stable disease, indicating potential effectiveness in treating certain pediatric solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. Moreno, L., Casanova, M., Chisholm, JC., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration. [2023]

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

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer. [2022]

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

Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. [2022]

8. 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]

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

A phase II trial of nab-Paclitaxel as second-line therapy in patients with advanced pancreatic cancer. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel in solid tumors: clinical development and future directions. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. [2019]