Ipatasertib + Chemotherapy for Cancer
Recruiting in Palo Alto (17 mi)
+220 other locations
Overseen ByReva K Basho
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Approved in 3 jurisdictions
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.
12345Is 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.
678910What 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.
1112131415Eligibility 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.Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (paclitaxel, ipatasertib)Experimental Treatment6 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of Michigan Health - Sparrow LansingLansing, MI
Carle on VermilionDanville, IL
University of South Alabama Mitchell Cancer InstituteMobile, AL
Kootenai Clinic Cancer Services - SandpointSandpoint, ID
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]The novel paclitaxel formulation (nanoparticle albumin-bound [nab] paclitaxel (Abraxane(®)) has recently been approved by the US FDA for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months after adjuvant chemotherapy. Apart from its superior efficacy, as demonstrated in the pivotal Phase III study, less toxicity compared with the traditional solvent-containing paclitaxel (Taxol(®)) seems to contribute to its favorable therapeutic index. While approved as a single agent, nab-paclitaxel may prove more effective in combination with either biologic agents and/or other cytotoxic chemotherapeutic agents, as summarized in this article.
A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma.
Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]Label="PURPOSE" NlmCategory="OBJECTIVE">Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC).
Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. [2022]Combination chemotherapy regimens including fluoropyrimidines as well as albumin-bound paclitaxel have shown promising results in patients with metastatic pancreatic adenocarcinoma (mPC). Based on the recently described excellent therapeutic index of capecitabine plus nab-paclitaxel in metastatic breast cancer, the present phase II trial was initiated.
Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. [2015]The results of several phase II and some phase III studies are now available in which the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and nonanthracycline agents are evaluated. The studies demonstrate the activity and feasibility of these combinations, which achieved response rates of 40% to 80% and median time to progression that exceeded 6 months. The potential role of these combinations compared with older non-paclitaxel-containing regimens, in improving quality of life, response rate, and survival in patients with metastatic breast cancer, however, await the results of prospective, randomized phase III trials. The next logical step, depending on the results of planned comparative trials, is to incorporate these combinations in the neoadjuvant and adjuvant settings.
Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. [2019]Abraxane is a novel Cremophor-free nanoparticle paclitaxel that has been demonstrated to improve efficacy in the treatment of solid tumors. We undertook this retrospective study to evaluate the efficacy and safety of Abraxane in the progressive or recurrent non-small cell lung cancer (NSCLC) patients.
Overview of Taxol safety. [2015]The safety profile of Taxol administered intravenously as a single agent has been established based on the experience of 655 patients. Of these patients, 253 were treated in nine phase I studies, and 402 were treated in eight disease-oriented phase II studies. Myelosuppression, specifically neutropenia, was the dose-limiting toxicity in all studies conducted in patients with solid tumors. Neutropenia was schedule dependent and was less severe when Taxol was administered via a 3-hour infusion. Severe hypersensitivity reactions were controlled in the phase II program with a premedication regimen consisting of dexamethasone, an antihistamine, and an H2 blocker. Cardiovascular toxicities were minimal and do not indicate constant electrocardiographic monitoring during Taxol infusions. Peripheral neuropathy was usually mild to moderate and dose related; however, it rarely caused treatment discontinuation. Additional adverse events associated with Taxol include arthralgia/myalgia, mucositis, nausea and vomiting, and alopecia.
Paclitaxel (taxol). [2019]Paclitaxel is a novel antineoplastic that effects cytotoxicity by promoting intracellular tubulin polymerization and stabilizes abnormal microtubule structures against depolymerization. Although its clinical development had been hampered by misconceptions about its pharmacology, its scarcity, difficulties extracting it from its natural source, formulation problems, and frequent severe hypersensitivity reactions, paclitaxel recently was approved for treatment-refractory ovarian cancer. Two major adverse effects are dosage- and schedule-related myelosuppression and mucositis. Neurotoxicity is directly related to both the individual and cumulative doses. Other relevant toxicities are hypersensitivity reactions, effects on cardiac rate and rhythm, arthralgias and myalgias, generalized hair loss, and mild nausea and emesis. Continuing clinical studies will evaluate paclitaxel as initial therapy for ovarian cancer and its utility in other malignancies. In addition, major efforts are under way to develop alternative sources to increase the availability of taxene analogs and reduce our dependence on yew species.
Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. [2020]Taxanes [paclitaxel, nab-paclitaxel (Abraxane, Celgene Corp, USA), and docetaxel]-used in the treatment of lung, breast, and head and neck cancers-have been associated with cutaneous adverse effects, including photodermatoses.
Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]Adding ipatasertib to abiraterone and prednisone/prednisolone significantly improved radiographic progression-free survival for patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN-loss tumours by immunohistochemistry in the IPATential150 trial (NCT03072238). Here we characterise the safety of these agents in subpopulations and assess manageability of key adverse events (AEs).
Clinical overview of the taxanes. [2022]Paclitaxel and docetaxel are taxane antineoplastic agents with broad antitumor activity. Since being introduced, they have become increasingly important in the treatment of a number of major solid tumors. Paclitaxel plus a platinum analog is now considered first-line therapy for advanced ovarian cancer, and both paclitaxel and docetaxel have significant activity as single agents in recurrent ovarian cancer. Docetaxel may be useful in some of these women with ovarian cancer who fail or progress after paclitaxel-containing treatments. Both drugs have significant response rates in the treatment of breast cancer and are options for patients with advanced disease, including anthracycline-refractory disease. Administration of taxanes in new combination regimens and as adjuvant therapy for breast cancer is under investigation; for example, the combination of paclitaxel and doxorubicin is highly active, and comparative studies of taxanes and anthracyclines should help clarify optimal treatment regimens in breast cancer. Both drugs have significant activity alone in the treatment of advanced non-small cell lung cancer (NSCLC) and head and neck cancers. For the former, paclitaxel-cisplatin is now standard treatment in cooperative group combination therapy trials. As a result of its radiosensitizing properties, paclitaxel is undergoing extensive evaluation as combined modality treatment for advanced NSCLC and head and neck cancer. Both taxanes will probably be useful in combination regimens in head and neck cancer. Research is continuing to define further their roles and relative usefulness in other malignancies.
[Evidenced-based medicine and future direction of Taxol]. [2015]Taxol was introduced for the clinical treatment of several solid tumor malignancies in the 1990s. It has been established that primary chemotherapy based on Taxol is the standard for non-small cell lung cancer and epithelial ovarian cancer. After initial chemotherapy containing doxorubicin, sequential administration of Taxol for advanced or metastatic breast cancer is recommended by the Food and Drug Administration in the United States. Taxol-based chemotherapy and/or concurrent chemoradiation for head and neck cancer, esophageal carcinoma, urothelial and prostate cancer are under investigation, but these trials have not produced evidence showing that they are superior to the present standard treatment for these malignancies. Although phase I/II trials of Taxol combined with new agents such as vinorelbine, topotecan, CPT-11 and others may demonstrate efficacy to a certain extent for some solid tumor malignancies, a phase III study will be required in the next stage. Taxol combined with other agents focusing on molecular targets will be an important approach in next decade. Inhibition of signal transduction by a noncytotoxic agent such as herceptine has the potential to enhance the cytotoxic effect of Taxo.
European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. [2019]Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown high clinical antitumor activity in several tumor types, including ovarian, breast, and lung carcinoma. Preclinical studies have shown that paclitaxel has an additive effect when combined with platinum compounds. Early clinical trials confirmed these data and established the dose range for both drugs. In recent years, several studies were developed in Europe using the combination of paclitaxel and platinum in non-small cell lung cancer, and four large randomized trials have been completed in Europe. The first study compared paclitaxel/cisplatin with teniposide/cisplatin, which was the control arm of the European Organization for Research and Treatment of Cancer at that time. The second study evaluated the benefit of the addition of paclitaxel to cisplatin. The third study compared paclitaxel/cisplatin with paclitaxel/carboplatin, and the fourth compared two doses of paclitaxel combined with carboplatin. Another large randomized study is currently being performed by the European Organization for Research and Treatment of Cancer. Combinations using paclitaxel-based regimens in the preoperative setting are under investigation. An ongoing European Organization for Research and Treatment of Cancer trial compares surgery with radiotherapy following various induction chemotherapy combinations, among which paclitaxel/platinum is one of the most frequently used. Another induction regimen is currently being evaluated by the University Medical School of Essen and Institut Gustave Roussy in Villejuif, France. In this trial, paclitaxel/cisplatin is delivered before etoposide/cisplatin and concurrent radiotherapy followed by surgery in locally advanced non-small cell lung cancer. Preclinical studies underline the radiosensitizing effect of paclitaxel, and many clinical studies are being conducted with radiotherapy in association with paclitaxel alone or in combination with platinum compounds. The use of paclitaxel in regimens without platinum and in triplet combinations is also being studied, and the optimal manner in which to administer this active agent clearly is of interest.
Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. [2015]Capecitabine, a tumor-activated oral fluoropyrimidine, and albumin-bound paclitaxel (ab-paclitaxel) have substantial single-agent activity in patients with metastatic breast cancer (MBC). Taxane and antimetabolite doublets have improved efficacy compared with single agents. This phase II open-label trial was designed to test the safety and efficacy of capecitabine and ab-paclitaxel in previously untreated MBC.
Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. Paclitaxel by 3-hour infusion plus doxorubicin by bolus proved to be a highly tolerable regimen, with overall remission rates in excess of 90% and complete remission rates approaching 50%. A paclitaxel plus cisplatin combination has been studied at numerous schedules and doses with variable activity and tolerability, although one group in Vancouver, Canada, reported an 85% overall response rate with the combination administered on a 14-day schedule in previously treated patients, most of whom had received doxorubicin. Paclitaxel also has been combined with cyclophosphamide, mitoxantrone, edatrexate, 5-fluorouracil, and other agents for the treatment of breast cancer. Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.