Ipatasertib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: GnRH agonists

Must not be taking: AKT inhibitors, CYP3A4/5 inducers

Disqualifiers: Breast cancer, KRAS mutations, 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: 4

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ipatasertib to determine its effectiveness in treating cancers with specific genetic changes known as AKT mutations. Ipatasertib aims to stop cancer cells from growing and potentially kill them. Suitable candidates for this trial have cancer with an AKT mutation, excluding breast cancer, and should not have certain other genetic mutations like KRAS or BRAF. The trial excludes individuals with a history of inflammatory bowel diseases or those who have previously taken similar treatments. Participants will take ipatasertib daily in cycles and undergo regular scans and tests to monitor progress. 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 all current medications, but you cannot have taken strong inhibitors or inducers of CYP3A4/5 within 2 weeks before starting the study. If you have castration-resistant prostate cancer, you should continue your current treatment with GnRH agonists or surgical castration, and you can continue abiraterone acetate/prednisone if you just progressed on it.

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

Research has shown that ipatasertib is generally well-tolerated by patients. One study found that when combined with treatments like palbociclib and fulvestrant, the side effects were expected and manageable with standard care.

Another study involving patients with specific genetic mutations reported that most of the 50 participants tolerated the treatment without severe issues. Although some side effects occurred, they were manageable for most.

Ipatasertib has also been tested in men with prostate cancer. When combined with abiraterone, it effectively slowed disease progression. The side effects were significant but expected, and doctors managed them well.

Overall, ipatasertib has demonstrated a consistent safety record across different studies. While side effects can occur, they are usually manageable. Patients should consult a healthcare provider to understand how this treatment might affect them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ipatasertib is unique because it targets a specific protein called Akt, which is involved in cancer cell growth and survival. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, ipatasertib is more selective, potentially leading to fewer side effects. Researchers are excited about this treatment because it offers a more targeted approach, potentially improving outcomes for patients with certain cancers that have been resistant to other treatments.

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

Research has shown that ipatasertib, the treatment under study in this trial, may help treat certain cancers with AKT mutations. In previous studies, adding ipatasertib to other cancer treatments reduced the risk of progression in prostate cancer patients. It also prolonged the period before breast cancer worsened when combined with fulvestrant. Evidence indicates that it works well against some cancers, such as endometrial cancer, when tumors have specific AKT mutations. These findings suggest that ipatasertib could be effective for certain cancers with these genetic changes. ^{2 4 6 7 8}

Who Is on the Research Team?

Kevin M Kalinsky

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with AKT genetic changes. It's open to those with multiple myeloma, various types of lymphoma, or solid tumors. Participants must have specific mutations and meet other health criteria not specified here.

Inclusion Criteria

I have prostate cancer that is not responding to hormone therapy and my testosterone levels are low.

My cancer has an AKT mutation.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

Exclusion Criteria

I do not have breast cancer.

I do not have a history of Crohn's, ulcerative colitis, or active diverticulitis.

I have never taken AKT inhibitor medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ipatasertib orally once daily on days 1-28 of each 28-day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Bi-weekly imaging and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes imaging and clinical assessments.

3 years

Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ipatasertib

Trial Overview The trial is testing Ipatasertib, a drug designed to inhibit a protein called AKT that may be involved in cancer cell growth. The study involves MRI and CT scans, tissue collection through biopsy, and monitoring how well the treatment works.

How Is the Trial Designed?

Group I: Treatment (ipatasertib) Experimental Treatment 5 Interventions

Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

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

Ipatasertib was found to be safe and tolerable in Japanese patients with solid tumors, with a maximum tolerated dose (MTD) of 600 mg/day when used alone and a maximum administered dose (MAD) of 400 mg/day when combined with abiraterone and prednisolone.

The study showed that ipatasertib led to stable disease in 53.3% of patients receiving it as monotherapy, and in combination with other treatments, one patient achieved a complete response, indicating potential efficacy in managing solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of ipatasertib as a single agent and in combination with abiraterone plus prednisolone in Japanese patients with advanced solid tumors. Doi, T., Fujiwara, Y., Matsubara, N., et al.[2023]

In the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

In a phase 2 trial involving 124 women with untreated triple-negative breast cancer, the addition of the AKT inhibitor ipatasertib to paclitaxel significantly improved median progression-free survival to 6.2 months compared to 4.9 months with placebo, indicating its potential efficacy in this patient population.

Ipatasertib was associated with some adverse events, notably diarrhea in 23% of patients, but no severe treatment-related complications or deaths were reported, suggesting a manageable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Kim, SB., Dent, R., Im, SA., et al.[2022]

The combination of the AKT inhibitor ipatasertib with paclitaxel significantly improved progression-free survival in patients with metastatic triple-negative breast cancer, especially in those with specific genetic alterations (PIK3CA/AKT1/PTEN).

Circulating tumor DNA (ctDNA) analysis showed that lower levels of ctDNA during treatment were associated with better outcomes, indicating that ctDNA could be a useful tool for monitoring treatment response and prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. Wongchenko, MJ., Kim, SB., Saura, C., et al.[2022]

The phase Ib study involving 122 patients demonstrated that the oral AKT inhibitor ipatasertib, when combined with chemotherapy or hormonal therapy, was generally well tolerated, with a safety profile similar to other AKT inhibitors, although some specific adverse effects like diarrhea and hyperglycemia were noted.

The recommended phase II doses for ipatasertib were established at 600 mg with mFOLFOX6 and 400 mg with paclitaxel, indicating a manageable safety profile and potential for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors. Isakoff, SJ., Tabernero, J., Molife, LR., et al.[2021]

Ipatasertib, when combined with chemotherapy regimens, was found to be safe and well-tolerated in patients with metastatic triple-negative breast cancer, with common side effects including neutropenia and diarrhea.

The overall response rates for ipatasertib in combination with chemotherapy were 29% for carboplatin/paclitaxel, 25% for carboplatin, and 33% for capecitabine/atezolizumab, with progression-free survival durations of 4.8, 3.9, and 8.2 months respectively, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer. Yuan, Y., Yost, SE., Cui, Y., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39884884/

Final Overall Survival and Molecular Data Associated with ... Ipatasertib addition to abiraterone significantly reduced the risk of disease progression in men with metastatic castration-resistant prostate cancer (mCRPC) ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0302283824027714

Final Overall Survival and Molecular Data Associated with ... Ipatasertib addition to abiraterone significantly reduced the risk of disease progression in men with metastatic castration-resistant prostate cancer (mCRPC) ...

3. onclive.com onclive.com/view/ipatasertib-plus-fulvestrant-demonstrates-significant-pfs-benefit-in-er-her2-metastatic-breast-cancer

Ipatasertib Plus Fulvestrant Demonstrates Significant PFS ... Ipatasertib in combination with fulvestrant (Faslodex) significantly prolonged progression-free survival (PFS) compared with placebo plus fulvestrant.

4. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-02089-4

Ipatasertib combined with non-taxane chemotherapy for ... Median PFS was 2.7 (95%CI, 1.5–4.1) and 3.8 (95%CI, 1.5–9.6) months; median OS was 15.5 (95%CI, 11.8–19.3) and 11.5 (95%CI, 8.8–25.1) months; ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3092

Ipatasertib in patients with AKT1/2/3 mutation-positive ... Conclusions: Treatment with ipatasertib led to a marked and durable antitumor activity in some tumor types such as endometrial cancer, but not ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41079728/

Pharmacokinetics, safety and tolerability of ipatasertib in ... The combination regimen of ipatasertib 300 mg with palbociclib and fulvestrant had a notable and manageable safety profile, that is generally ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39721851/

A Phase I Study of the Pharmacokinetics and Safety ... The current clinical trial aimed to assess the pharmacokinetic properties, safety, and tolerability of ipatasertib administered to Chinese patients with ...

8. clinical-genitourinary-cancer.com clinical-genitourinary-cancer.com/article/S1558-7673(23)00001-0/fulltext

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo ... Adding ipatasertib to abiraterone and prednisone/prednisolone significantly improved radiographic progression-free survival for patients with metastatic ...