Ipatasertib + Chemotherapy for Ovarian Cancer

Not currently recruiting at 9 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled diabetes, Lung disease, others

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

Compensation: Varies

Number of Visits: 5

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for advanced ovarian cancer, testing the safety and optimal dosage of ipatasertib (an experimental drug) alongside chemotherapy drugs paclitaxel and carboplatin. Ipatasertib may inhibit cancer cell growth by blocking certain necessary enzymes. The trial seeks participants with stage III or IV ovarian cancer who have not yet received treatment and whose disease cannot currently be surgically removed. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take strong CYP3A inhibitors or inducers within 2 weeks before joining the trial. It's important to discuss your current medications with the trial team to avoid any potential interactions.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot take strong CYP3A inhibitors or inducers within 2 weeks before joining the trial, as they may interact with the study drugs.

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

Research shows that the combination of ipatasertib, paclitaxel, and carboplatin has been tested for safety and side effects. In earlier studies, most patients tolerated this combination well. Paclitaxel and carboplatin, common chemotherapy drugs, have well-known safety records and are often used to treat ovarian cancer. They are generally considered safe, with known side effects.

Adding ipatasertib to these drugs has shown promising safety results. Some patients experienced mild to moderate side effects, but these are usually manageable. Studies have not found any unexpected severe side effects with this combination.

Since this trial is in an early stage, it aims to find the best dose and understand any possible side effects. While the treatment is expected to be safe, the complete safety profile is still under study. Participants in this trial will be closely monitored to ensure their safety and to manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ipatasertib with chemotherapy for ovarian cancer because it introduces a new mechanism of action. Unlike the standard treatments which primarily include chemotherapy drugs like carboplatin and paclitaxel that attack cancer cells directly, ipatasertib targets a specific pathway known as the AKT pathway, which plays a crucial role in cancer cell growth and survival. By inhibiting this pathway, ipatasertib may enhance the effectiveness of chemotherapy and potentially lead to better outcomes for patients. This innovative approach offers hope for improved treatment responses in ovarian cancer.

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

Research has shown that ipatasertib, an oral medication, has potential when combined with the chemotherapy drugs carboplatin and paclitaxel. Studies have found that this combination can inhibit cancer cell growth by blocking essential enzymes. Previous research on other cancers, such as triple-negative breast cancer, demonstrated positive results when using ipatasertib with chemotherapy like paclitaxel. In this trial, participants will receive a combination of carboplatin, paclitaxel, and ipatasertib to assess its effectiveness in treating ovarian cancer. Early evidence suggests that adding ipatasertib may enhance the treatment's effectiveness, potentially slowing tumor growth more effectively than chemotherapy alone. ^{1 4 5 6 7}

Who Is on the Research Team?

Katherine C Fuh

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with stage III or IV epithelial ovarian cancer that's inoperable and hasn't been treated yet. Participants must have good performance status, meet specific blood count and organ function criteria, not be pregnant or breastfeeding, agree to use two forms of birth control, and can't have had prior treatments targeting the PI3K/AKT/mTor pathway.

Inclusion Criteria

I have a history of heart issues or have been treated with heart-toxic drugs.

My condition requires chemotherapy before surgery to remove my tumor.

I have chronic hepatitis B but it's undetectable with my current treatment.

Exclusion Criteria

I am currently on IV antibiotics for an infection.

I haven't taken strong CYP3A affecting drugs recently.

I have had radiation therapy to my abdomen or pelvis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel and carboplatin intravenously on day 1 of each 21-day cycle, along with daily oral ipatasertib, for up to 3 cycles

9 weeks

3 visits (in-person) for IV treatment, daily oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

90 days

2 visits (in-person) at 30 and 90 days post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Ipatasertib
• Paclitaxel

Trial Overview The study tests the safety and optimal dose of ipatasertib combined with standard chemotherapy drugs paclitaxel and carboplatin. Ipatasertib may block enzymes needed for tumor growth while the chemo drugs aim to stop or slow down tumor cell division, potentially improving treatment outcomes.

How Is the Trial Designed?

Group I: Treatment (paclitaxel, carboplatin, ipatasertib) Experimental Treatment 4 Interventions

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive ipatasertib PO QD until 24 hours before surgery in the absence of disease progression or unacceptable toxicity.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a study involving 247 patients with advanced ovarian cancer, both treatment regimens (standard carboplatin plus paclitaxel and alternating carboplatin/cisplatin plus paclitaxel) showed similar efficacy, with no significant differences in progression-free survival (PFS) or overall survival.

Both regimens were well tolerated, indicating that while the alternating regimen does not provide additional benefits, it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study. Aravantinos, G., Fountzilas, G., Kosmidis, P., et al.[2022]

In a phase 2 study involving 76 patients with suboptimal residual ovarian cancer, the combination of intraperitoneal carboplatin and dose-dense paclitaxel resulted in a high objective clinical response rate of 83.1%.

The treatment demonstrated promising median progression-free survival of 18.3 months and overall survival of 55.5 months, indicating its efficacy as a front-line chemotherapy option, although it was associated with significant side effects like neutropenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in front-line treatment of suboptimal residual ovarian cancer. Hasegawa, K., Shimada, M., Takeuchi, S., et al.[2021]

In a trial involving 59 women with advanced ovarian cancer, the combination of paclitaxel and carboplatin resulted in a high response rate of 72%, indicating effective treatment for this patient population.

Patients experienced significant improvements in quality of life during the outpatient treatment, with median survival times of 30.1 months for those with measurable disease, suggesting that this regimen is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient taxol and carboplatin chemotherapy for suboptimally debulked epithelial carcinoma of the ovary results in improved quality of life: an Eastern Cooperative Oncology Group Phase II Study (E2E93). Schink, JC., Weller, E., Harris, LS., et al.[2015]

Weekly paclitaxel and cisplatin chemotherapy (wTP) was found to be safe and well-tolerated in 86 patients with ovarian cancer who previously experienced hypersensitivity reactions to carboplatin, with 83% successfully receiving at least one cycle of treatment.

The treatment showed promising efficacy, with a median progression-free survival of 10.9 months and overall survival of 25.9 months, indicating that wTP can be an effective alternative for patients unable to tolerate carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin. Tate, S., Nishikimi, K., Matsuoka, A., et al.[2021]

In a study of 7 heavily pre-treated ovarian cancer patients, weekly administration of paclitaxel showed some efficacy, resulting in 2 cases of partial remission and 3 cases with no change in disease status.

Despite some patients experiencing peripheral neuropathy and mild hematological toxicity, the overall treatment was considered effective in maintaining quality of life for patients resistant to previous chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study on the efficacy of weekly paclitaxel administration for platinum-resistant epithelial ovarian carcinoma]. Fujii, K., Takano, M., Okamoto, S., et al.[2015]

The combination of paclitaxel, carboplatin, and gemcitabine was found to be feasible and active in treating previously untreated ovarian cancer, with 10 out of 14 patients showing an objective response.

While the treatment caused significant hematological toxicities, such as neutropenia (76.3%) and leukopenia (70.9%), serious complications like febrile neutropenia were rare (1.8%), indicating that the regimen is manageable and can proceed to further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8). du Bois, A., Belau, A., Wagner, U., et al.[2022]

In advanced ovarian cancer, the combination of paclitaxel and carboplatin is the standard first-line treatment, showing effectiveness comparable to paclitaxel and cisplatin, while being better tolerated by patients.

For recurrent ovarian cancer, recent trials suggest that paclitaxel/carboplatin may be more effective than single-agent carboplatin, highlighting the importance of ongoing research into new treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents. Ozols, RF.[2022]

Chemotherapy following surgical debulking is crucial for treating advanced ovarian cancer, with about 75% of patients responding well to platinum-based drugs, but relapse rates are high, exceeding 50%.

Intraperitoneal (IP) chemotherapy, which delivers drugs directly to the tumor site, is being explored as a promising approach for both initial and recurrent cases of ovarian cancer, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging intraperitoneal (IP) drugs for ovarian cancer treatment. Muggia, FM.[2007]

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[2019]

In a study of 22 high-risk ovarian cancer patients treated with adjuvant paclitaxel and carboplatin, the treatment was generally well tolerated, with manageable side effects and a high completion rate of therapy (77% without delays).

The treatment led to significant clinical outcomes, with 16 out of 19 patients with advanced disease achieving complete clinical remission after six cycles, indicating strong efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and short-infusion paclitaxel in high-risk and advanced-stage ovarian carcinoma. Coleman, RL., Bagnell, KG., Townley, PM.[2015]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05276973

NCT05276973 | Testing the Addition of Ipatasertib to ... This phase I/IB trial tests the safety, side effects, and best dose of ipatasertib in combination with paclitaxel and carboplatin in treating patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9930841/

Ipatasertib, an oral AKT inhibitor, in combination with ... Our results indicate that IPAT combined with carboplatin at low doses was more effective at reducing proliferation, inducing apoptosis and causing cellular ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.1078

A phase I/IB study of ipatasertib in combination with ... Ipatasertib (ipat) is an AKT inhibitor which has shown efficacy in combination with paclitaxel and atezolizumab in patients with triple negative breast cancer ...

4. withpower.com withpower.com/trial/phase-1-stage-iiia-ovarian-cancer-ajcc-v8-6-2022-de084

Ipatasertib + Chemotherapy for Ovarian Cancer The combination of Carboplatin and Paclitaxel has been widely studied and is generally considered safe for treating ovarian cancer, though it can cause side ...

5. academic.oup.com academic.oup.com/oncolo/article/28/7/e498/7110249

Phase I Trial of Ipatasertib Plus Carboplatin ... - Oxford Academic This trial evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10322142/

Phase I Trial of Ipatasertib Plus Carboplatin ... This trial evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients ...

7. nrgoncology.org nrgoncology.org/Clinical-Trials/Protocol/nrg-gy025-1?filter=nrg-gy025-1

NRG-GY027 NRG-GY027: PHASE I/IB SAFETY AND PHARMACODYNAMIC STUDY OF NEOADJUVANT (NACT) PACLITAXEL AND CARBOPLATIN WITH IPATASERTIB AS INITIAL THERAPY OF OVARIAN CANCER ...