Ipatasertib + Chemotherapy for Ovarian Cancer

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

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 stage III or IV epithelial ovarian cancer. Ipatasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Paclitaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Giving ipatasertib in combination with paclitaxel and carboplatin may lower the chance of the tumor growing or spreading for longer than the paclitaxel and carboplatin alone.

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.

What data supports the idea that Ipatasertib + Chemotherapy for Ovarian Cancer is an effective treatment?

The available research shows that combining paclitaxel and carboplatin is a standard and effective treatment for ovarian cancer. It is noted for being highly active in patients with platinum-resistant ovarian cancer. Studies have shown that this combination is at least as effective as other similar treatments and is better tolerated, meaning patients experience fewer side effects. While the specific combination of Ipatasertib with chemotherapy isn't directly mentioned, the effectiveness of paclitaxel and carboplatin suggests that adding Ipatasertib could potentially enhance treatment outcomes. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination of Ipatasertib, Carboplatin, and Paclitaxel for ovarian cancer?

Research shows that the combination of paclitaxel and carboplatin is a standard and effective treatment for advanced ovarian cancer, with studies indicating it is well-tolerated and improves survival. Paclitaxel is particularly effective in patients who are resistant to platinum-based treatments, making it a valuable part of the combination therapy. ^{1 2 3 4 5}

What safety data exists for the treatment of ovarian cancer with Ipatasertib and chemotherapy?

The safety data for chemotherapy involving carboplatin and paclitaxel in ovarian cancer treatment is well-documented. Studies have evaluated the tolerability, toxicity, and activity of these drugs in various combinations. Paclitaxel, in combination with platinum compounds like carboplatin, is a standard treatment for advanced ovarian cancer. Research has focused on dose intensity, administration schedules, and hypersensitivity reactions. However, specific safety data for the combination of Ipatasertib with these chemotherapy agents is not detailed in the provided research. ^{1 3 6 7 8}

Is the combination of Ipatasertib, Carboplatin, and Paclitaxel safe for humans?

The combination of Carboplatin and Paclitaxel has been widely studied and is generally considered safe for treating ovarian cancer, though it can cause side effects like hypersensitivity reactions (allergic reactions) and other toxicities. Ipatasertib's safety profile in combination with these drugs is not detailed in the provided studies, but these drugs are typically tested for safety in clinical trials before being used together. ^{1 3 6 7 8}

Is the drug combination of Carboplatin, Ipatasertib, and Paclitaxel promising for ovarian cancer?

Yes, the combination of Carboplatin and Paclitaxel is already a standard and effective treatment for ovarian cancer, especially in advanced cases. Adding Ipatasertib, which is a new drug, could potentially make the treatment even more effective by targeting cancer cells in a different way. ^{1 2 9 10 11}

What makes the drug combination of Ipatasertib, Carboplatin, and Paclitaxel unique for treating ovarian cancer?

This treatment is unique because it combines Ipatasertib, a newer drug that targets specific cancer cell pathways, with the standard chemotherapy drugs Carboplatin and Paclitaxel, which are already known to be effective in treating ovarian cancer. This combination aims to enhance the effectiveness of treatment, especially in cases where the cancer is resistant to standard therapies. ^{1 2 9 10 11}

Research Team

Katherine C Fuh

Principal Investigator

NRG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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]

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]

References

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

Treatment of ovarian cancer: current status. [2015]

2. England 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. [2022]

3. United States 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). [2022]

4. United States 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). [2015]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin. [2021]

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

USA update on paclitaxel in ovarian cancer. [2019]

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

Carboplatin and short-infusion paclitaxel in high-risk and advanced-stage ovarian carcinoma. [2015]

9. England 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. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

[Clinical study on the efficacy of weekly paclitaxel administration for platinum-resistant epithelial ovarian carcinoma]. [2015]

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

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