Ipatasertib + Chemotherapy for Cancer

Recruiting at 230 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: KRAS mutation, Brain metastases, Diabetes, Lung disease, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: up to 35 months

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy (paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced) or from where it first started (primary site) to other places in the body (metastatic), and has PTEN and AKT genetic changes. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy, such as Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of ipatasertib to paclitaxel in solid tumors with PTEN and AKT genetic changes could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus ipatasertib will shrink this type of cancer or stop its growth.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take medications that are strong inhibitors or inducers of CYP3A enzymes. It's important to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the drug combination of Ipatasertib and chemotherapy for cancer?

Research shows that nab-paclitaxel (Abraxane), a component of the treatment, has been effective in treating metastatic breast and pancreatic cancers, with studies indicating it works well in combination with other drugs and has less toxicity compared to traditional formulations. ^{1 2 3 4 5}

Is the combination of Ipatasertib and chemotherapy generally safe for humans?

Ipatasertib has been studied in combination with other drugs like abiraterone for prostate cancer, showing manageable side effects. Paclitaxel, a chemotherapy drug, has known side effects like low white blood cell counts, mild nerve damage, and allergic reactions, but these are often manageable with premedication. ^{6 7 8 9 10}

What makes the drug combination of Ipatasertib and Paclitaxel unique for cancer treatment?

The combination of Ipatasertib and Paclitaxel is unique because Ipatasertib targets specific molecular pathways involved in cancer cell growth, potentially enhancing the effectiveness of Paclitaxel, which is a well-established chemotherapy drug. This approach aims to improve treatment outcomes by combining a targeted therapy with traditional chemotherapy. ^{11 12 13 14 15}

Research Team

Reva K Basho

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

Adults with solid tumors that can't be surgically removed, have spread, and show an AKT genetic mutation. They must have progressed after taxane-based therapy within 6 months and meet specific health criteria including organ function tests. Excluded are those who've had prior AKT inhibitors, certain mutations, uncontrolled illnesses or bowel inflammation, or are pregnant.

Inclusion Criteria

Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191

My cancer has an AKT mutation according to the ComboMATCH test.

I am enrolled in EAY191 and assigned to ComboMATCH for EAY191-S3 due to a specific mutation.

Exclusion Criteria

I can swallow pills without any issues.

Participants with known diabetes mellitus must meet specific criteria

My condition did not worsen within 6 months after receiving taxane-based therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive paclitaxel intravenously on days 1, 8, and 15 and ipatasertib orally on days 1-21 of each 28-day cycle, for up to 35 cycles

up to 35 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up until death or 3 years after registration

up to 3 years

Regular follow-up visits

Treatment Details

Interventions

• Ipatasertib
• Paclitaxel

Trial Overview The trial is testing the combination of chemotherapy (paclitaxel) with a targeted drug called Ipatasertib in patients whose solid tumors carry an AKT mutation. The goal is to see if this combo can shrink these cancers or stop their growth more effectively than standard treatments.

Participant Groups

Group I: Treatment (paclitaxel, ipatasertib) Experimental Treatment 6 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

In a phase II trial involving 30 patients with untreated metastatic pancreatic adenocarcinoma, the combination of capecitabine and nab-paclitaxel demonstrated a promising objective response rate of 41.4% and a disease control rate of 76%.

The treatment was well tolerated, with most patients able to escalate the nab-paclitaxel dose after the first course, and the most common adverse events were manageable, including sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. Scheithauer, W., Kornek, G., Prager, G., et al.[2022]

Combination therapies using paclitaxel with non-anthracycline agents have shown promising response rates between 40% to 80% and median time to progression exceeding 6 months in phase II and III studies.

Further research through prospective, randomized phase III trials is needed to confirm the benefits of these combinations over older treatments, particularly regarding quality of life, response rates, and survival in metastatic breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. Perez, EA.[2015]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

A woman with non-small cell lung cancer developed a photodistributed dermatitis as a side effect of nab-paclitaxel therapy, which worsened with each treatment cycle, highlighting the potential for skin reactions in patients receiving taxane chemotherapy.

The patient's condition improved with topical corticosteroids and strict sun avoidance, indicating that while photodermatoses can occur with taxane treatments, they can be managed effectively without necessarily stopping chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. Beutler, BD., Cohen, PR.[2020]

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]

Paclitaxel and docetaxel are effective treatments for various solid tumors, with paclitaxel now considered first-line therapy for advanced ovarian cancer and both drugs showing significant activity in recurrent ovarian cancer.

Both taxanes are also effective in treating breast cancer and advanced non-small cell lung cancer (NSCLC), with ongoing research exploring their use in combination therapies and as adjuvant treatments to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical overview of the taxanes. Goldspiel, BR.[2022]

Taxol has been established as a standard treatment for non-small cell lung cancer and epithelial ovarian cancer, and is recommended for use after doxorubicin in advanced or metastatic breast cancer.

While Taxol is being investigated for use in other cancers like head and neck and prostate cancer, current trials have not shown it to be superior to existing treatments, indicating a need for further phase III studies and exploration of combinations with targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evidenced-based medicine and future direction of Taxol]. Hatae, M., Nakamura, T., Ohnishi, Y.[2015]

Paclitaxel has demonstrated strong antitumor activity in various cancers, including ovarian, breast, and lung carcinoma, especially when combined with platinum compounds like cisplatin and carboplatin.

Recent large randomized trials in Europe have explored the effectiveness of paclitaxel in combination with platinum for treating non-small cell lung cancer, showing promising results and leading to ongoing studies on its use in preoperative settings and with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. Novello, S., Le Chevalier, T.[2019]

In a phase II trial involving 50 patients with previously untreated metastatic breast cancer, the combination of capecitabine and albumin-bound paclitaxel demonstrated a significant overall response rate of 61%, with a clinical benefit rate of 76.1%.

The treatment was well tolerated, with a median progression-free survival of 10.6 months and median overall survival of 19.9 months, although some patients experienced grade 3 adverse events like pain and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Schwartzberg, LS., Arena, FP., Mintzer, DM., et al.[2015]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

4. China pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. [2022]

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

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. [2015]

6. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. [2019]

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

Overview of Taxol safety. [2015]

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

Paclitaxel (taxol). [2019]

9. Austria pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. [2020]

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

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

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

Clinical overview of the taxanes. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

[Evidenced-based medicine and future direction of Taxol]. [2015]

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

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. [2019]

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

Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. [2015]

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

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]