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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well ipatasertib works in treating patients with cancer that has certain genetic changes called AKT mutations. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of cancer cells and may kill them.

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.

What data supports the effectiveness of the drug Ipatasertib for cancer?

Research shows that Ipatasertib, when combined with other treatments, improved progression-free survival (the time during which the cancer does not get worse) in patients with certain types of breast and prostate cancer. This suggests that Ipatasertib may help slow down cancer progression in these conditions. ^{1 2 3 4 5}

What makes the drug ipatasertib unique for cancer treatment?

Ipatasertib is unique because it is a highly selective inhibitor of Akt, a protein kinase often activated in cancers, and it is taken orally. This drug is being studied for its potential to enhance the effectiveness of chemotherapy and hormonal therapy in various solid tumors, including triple-negative breast cancer, by targeting a specific pathway involved in cancer cell growth. ^{1 2 6 7 8}

Research Team

Kevin M Kalinsky

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Treatment (ipatasertib) Experimental Treatment 5 Interventions

Patients receive ipatasertib 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+

Findings from Research

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]

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]

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]

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]

References

1. Germany 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. [2023]

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

Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors. [2021]

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

Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer. [2023]

4. United States 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. [2022]

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

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]

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

The Absolute Bioavailability and Absorption, Metabolism, and Excretion of Ipatasertib, a Potent and Highly Selective Protein Kinase B (Akt) Inhibitor. [2023]

7. England pubmed.ncbi.nlm.nih.gov

FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer. [2020]

8. England 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. [2022]