Serabelisib + Diet/Nab-paclitaxel for Solid Cancers

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, serabelisib (an experimental drug), combined with a special diet and sometimes nab-paclitaxel (a chemotherapy medication), to determine its safety and effectiveness in treating solid tumors. Researchers aim to discover if this combination can reduce side effects and enhance cancer treatment. Individuals with certain types of solid tumors, such as endometrial or ovarian cancer, who have specific genetic mutations and have not succeeded with other treatments, might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research has shown that serabelisib, a PI3K inhibitor, is generally safe and well-tolerated when combined with paclitaxel. Earlier studies reported only minor side effects among participants, indicating that most patients can handle the treatment well.

Nab-paclitaxel, another drug tested in the trial, has also proven safe for patients with endometrial and ovarian cancer. In studies involving 43 patients who switched to nab-paclitaxel, no allergic reactions occurred, suggesting it is a safe choice for these cancer types.

Overall, both serabelisib and nab-paclitaxel have been tested in people and are generally safe, with side effects that are usually mild. This trial aims to further enhance their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about serabelisib as a treatment for solid cancers because it offers a novel approach compared to standard therapies like chemotherapy or targeted treatments. Unlike typical treatments, serabelisib is an oral medication that targets the PI3K pathway, which is involved in cell growth and survival, potentially offering a more precise attack on cancer cells. Additionally, its use alongside an Insulin Suppressing Diet could enhance its effectiveness by altering the tumor's metabolic environment. For certain cancers, serabelisib combined with nab-paclitaxel—a chemotherapy drug—adds another layer of potential effectiveness, aiming to improve outcomes where standard treatments may fall short.

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

Research has shown that serabelisib, one of the treatments in this trial, holds promise for treating solid tumors, especially when combined with other treatments. In this trial, some participants will receive serabelisib with an Insulin Suppressing Diet, while others will also receive nab-paclitaxel. Studies have found that combining serabelisib with paclitaxel is safe and generally well-tolerated, with early results indicating effectiveness for patients with hard-to-treat cancers. Nab-paclitaxel, when combined with other treatments, has proven effective for certain cancers, such as ovarian cancer, and has extended patient survival. Together, these treatments might offer a strong approach to fighting solid tumors, with early evidence suggesting they could enhance anticancer effects when used together. ^{2 3 5 6 7}

Who Is on the Research Team?

Vicky Makker

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11176914/

A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) ... The endometrial cancer–expansion cohort consisted of women 18 years of age or older with histologically confirmed endometrial cancer, including ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02020707

Nab-Paclitaxel and Bevacizumab in Treating Patients With ... This phase I trial studies the side effects and best dose of nab-paclitaxel and bevacizumab in treating patients with stage IV melanoma that cannot be ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10323297/

Effectiveness and safety of nab-paclitaxel and platinum as first ... Abstract. Objective. To evaluate the effectiveness and safety of nab-paclitaxel plus platinum as first-line chemotherapy for ovarian cancer (OC).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825824010461

A phase 2 feasibility study of nab-paclitaxel and ... Dose-dense nab-paclitaxel on day 1, 8 with day 1 carboplatin every 3 weeks is feasible (6-cycle completion rate of 82.6%).

5. esmo.org esmo.org/oncology-news/adding-relacorilant-to-nab-paclitaxel-prolongs-survival-compared-with-a-weekly-taxane-in-patients-with-platinum-resistant-epithelial-ovarian-cancer

Adding Relacorilant To Nab-paclitaxel Prolongs Survival ... The addition of relacorilant to nab-paclitaxel for patients with platinum-resistant epithelial ovarian cancer showed a statistically significant improvement in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11350462/

Safety of nab-paclitaxel following an allergic reaction to ... No allergic reactions were noted in 43 patients with endometrial or ovarian cancer following the transition to nab-paclitaxel. •. Transition to ...

7. ajmc.com ajmc.com/view/relacorilant-plus-nab-paclitaxel-improves-outcomes-in-platinum-resistant-ovarian-cancer-brian-slomovitz-md

Relacorilant Plus Nab-Paclitaxel Improves Outcomes in ... Relacorilant combined with nab-paclitaxel (Abraxane) significantly improved progression-free and overall survival in patients with platinum-resistant ovarian ...