Taselisib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PI3K inhibitors, Akt inhibitors

Disqualifiers: Breast cancer, KRAS mutations, diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taselisib can shrink or halt the growth of certain cancers with a specific genetic change called the PIK3CA mutation. Taselisib blocks a protein that may be necessary for cancer cell growth. It may suit patients diagnosed with a PIK3CA-mutated cancer, excluding breast cancer, who have not undergone certain previous cancer treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have diabetes that requires medication, you may not be eligible to participate.

Is there any evidence suggesting that taselisib is likely to be safe for humans?

Research has shown that taselisib presents both potential benefits and challenges. In one study, 34 out of 68 patients experienced serious side effects, though these were not life-threatening. Another study found that even at a low dose, taselisib caused negative side effects, despite its promise in treating certain conditions.

On a positive note, early research suggested that taselisib had a more acceptable safety profile in smaller trials with patients who had advanced solid tumors, indicating that most patients initially did not experience severe side effects.

Overall, taselisib has caused serious side effects in several studies, but early signs suggest it might be more tolerable in specific cases. Prospective trial participants should consider these findings and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Taselisib is unique because it targets a specific pathway in cancer cells known as the PI3K pathway, which is often involved in tumor growth and survival. Unlike standard chemotherapy or hormone therapies that broadly attack cancer cells, taselisib's precision allows it to interfere directly with cancer cell signaling, potentially leading to fewer side effects. Researchers are excited about this treatment because targeting the PI3K pathway could offer a more effective and personalized approach to combating certain cancers, particularly those resistant to existing therapies.

What evidence suggests that taselisib might be an effective treatment for cancer?

Research has shown that taselisib may help treat cancers with a PIK3CA mutation. In one study, patients taking taselisib lived longer without their cancer worsening compared to those on a placebo. Another study found that taselisib slowed tumor growth and extended patients' overall survival. While these results are promising, some patients experienced significant side effects. Overall, taselisib shows potential as a treatment for certain types of cancer by blocking a protein essential for cancer cell growth. ^{1 2 4 6 7}

Who Is on the Research Team?

Ian E Krop

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with various cancers, including blood and solid tumors, who have a specific genetic change (PIK3CA mutation). They must not have diabetes requiring medication, no history of inflammatory bowel disease or certain heart conditions. Prior treatment with mTOR inhibitors is okay but no prior therapy with PI3K/mTOR or Akt inhibitors.

Inclusion Criteria

I have been treated with an mTOR inhibitor before.

My fasting blood sugar level is 125 mg/dL or lower.

My heart's pumping ability is normal according to recent tests.

Exclusion Criteria

My cancer does not have KRAS or PTEN mutations.

I do not have squamous cell lung cancer with PIK3CA mutations eligible for Lung-MAP.

I do not have a history of inflammatory bowel diseases like Crohn's or ulcerative colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive taselisib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Every 2 cycles for the first 26 cycles, then every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Taselisib

Trial Overview Researchers are testing Taselisib's effectiveness on cancers with the PIK3CA mutation. This phase II trial aims to see if Taselisib can shrink these cancers or halt their growth by blocking a protein essential for cancer cell development.

How Is the Trial Designed?

Group I: Treatment (taselisib) Experimental Treatment 1 Intervention

Patients receive taselisib 4 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the phase III SANDPIPER study involving 516 postmenopausal women with PIK3CA-mutant breast cancer, taselisib combined with fulvestrant significantly improved progression-free survival (7.4 months) compared to placebo plus fulvestrant (5.4 months), indicating its efficacy in this patient population.

Despite the efficacy in extending progression-free survival, the taselisib combination had a concerning safety profile, with higher rates of serious adverse events (32.0% vs. 8.9% in placebo) and more treatment discontinuations (16.8% vs. 2.3% in placebo), suggesting limited clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial. Dent, S., Cortés, J., Im, YH., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11179085/

Phase Ib dose-escalation trial of taselisib (GDC-0032) in ... Treatment was associated with significant toxicities, as 34 out of 68 patients experienced grade ≥3 adverse events (AEs) attributed to ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)43124-2/fulltext

Phase III randomized study of taselisib or placebo with ... INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% ...

3. nature.com nature.com/articles/s41436-021-01290-y

Safety and efficacy of low-dose PI3K inhibitor taselisib in ... Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients.

4. aacrjournals.org aacrjournals.org/clincancerres/article/27/2/447/83374/Phase-I-Basket-Study-of-Taselisib-an-Isoform

Phase I Basket Study of Taselisib, an Isoform-Selective PI3K ... Conclusions: Taselisib had limited activity in the tumor types tested and is no longer in development. This genome-driven study improves understanding of the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4270135/

Taselisib, a selective inhibitor of PIK3CA, is highly effective on ... Taselisib treatment resulted in a dramatically slower rate of tumor growth and a significant improvement in OS (P=0.007 and P<0.0001 respectively). These in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8865530/

Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors ... Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in PIK3CA-mutant breast cancer.

7. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/taselisib

Taselisib - an overview | ScienceDirect Topics Preliminary phase Ia clinical data demonstrated a favorable safety profile and signs of activity in 34 patients with locally advanced or metastatic solid tumors ...