Palbociclib + Gedatolisib for Solid Cancers
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Dana-Farber Cancer Institute
Must not be taking: CYP3A4 inhibitors, QT prolonging drugs
Disqualifiers: Diabetes, Brain metastases, Infections, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This research study is studying a combination of drugs as a possible treatment for cancer that might have a specific change in the phosphatidylinositol-3 phosphate (PI3K) pathway.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop all current medications, but you cannot use strong CYP3A4 inhibitors/inducers, medications metabolized by UGT1A9 or CYP2D6, drugs that prolong QT interval, or proton pump inhibitors. Check with the study team for specific guidance.
What data supports the idea that Palbociclib + Gedatolisib for Solid Cancers is an effective drug?
The available research does not provide specific data on the effectiveness of Palbociclib + Gedatolisib for Solid Cancers. Instead, it focuses on another drug, Gefitinib, which has shown effectiveness in treating non-small-cell lung cancer and other solid tumors. Gefitinib has demonstrated significant efficacy, with a 75% response rate in colorectal cancer when combined with standard chemotherapy, compared to 55% with standard therapy alone. However, there is no direct information on Palbociclib + Gedatolisib in the provided research.12345
What safety data is available for the combination of Palbociclib and Gedatolisib in solid cancers?
The provided research does not contain specific safety data for the combination of Palbociclib (Ibrance) and Gedatolisib (PF-05212384) in solid cancers. The studies focus on other drugs such as Neratinib and Ibrutinib, which are not relevant to the safety profile of Palbociclib and Gedatolisib.678910
Is the drug Gedatolisib, combined with Palbociclib, a promising treatment for solid cancers?
Eligibility Criteria
Adults with advanced squamous cell lung, pancreatic, head & neck cancers or solid tumors potentially linked to PI3K-pathway changes. They must have acceptable organ function and blood counts, no severe diabetes or heart conditions, not be on certain drugs affecting liver enzymes or the heart's rhythm, and agree to use contraception.Inclusion Criteria
My cancer has spread, can't be surgically removed, and doesn't respond to standard treatments.
I can take care of myself but might not be able to do heavy physical work.
I am 18 years old or older.
See 6 more
Exclusion Criteria
I have had chemotherapy or radiotherapy recently.
I am currently using or might need specific medications or special foods.
I do not have brain metastases needing treatment.
See 10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Palbociclib orally once daily on Days 1-21 and Gedatolisib intravenously once weekly during 4-week cycles
2 years
Weekly visits for Gedatolisib administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 months
Treatment Details
Interventions
- Gedatolisib (PI3K/mTOR Inhibitor)
- Palbociclib (CDK4/6 Inhibitor)
Trial OverviewThe trial is testing a drug combo of Palbociclib and Gedatolisib for treating advanced cancers. It aims to see if these drugs can help patients whose cancer might be affected by specific genetic changes in the PI3K pathway.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Combination Of Palbociclib and GedatolisibExperimental Treatment2 Interventions
* Palbociclib will be administered orally once daily on Days 1-21 for each of the 4-week cycles at a pre-determined dose.
* Gedatolisib will be administered intravenously once weekly on the first day for each of the four weeks during the 4-week cycles at a pre-determined dose.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Beth Israel Deaconess Medical CenterBoston, MA
Massachusetts General HospitalBoston, MA
Dana Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
Dana-Farber Cancer InstituteLead Sponsor
PfizerIndustry Sponsor
References
[Gefitinib versus Erlotinib as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer]. [2018]To compare the efficacy of the erlotinib versus gefitinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.
Erlotinib in the treatment of advanced non-small cell lung cancer: an update for clinicians. [2022]Inhibition of epidermal growth factor receptor (EGFR) has become an important target in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib, two small molecular agents that target the tyrosine kinase domain of the EGFR, were approved in many countries for the treatment of locally advanced or metastatic NSCLC as a second- or third-line regimen. Since then, randomized trials have evaluated the role of these two targeted agents alone or combined with chemotherapy in maintenance and first-line settings. This review summarizes the results of recent clinical trials with these tyrosine kinase inhibitors, with a focus on erlotinib, as first-line treatment towards a form of personalized medicine aimed at improving clinical outcome in advanced NSCLC.
The role of gefitinib in lung cancer treatment. [2018]Gefitinib (Iressa) is a novel targeted therapy that inhibits the tyrosine kinase activity of the epidermal growth factor receptor by competitively blocking the ATP binding site. In preclinical studies gefitinib has shown potent activity in a number of tumor models, including several lung cancer cell lines and xenografts. Two large randomized Phase II studies (IDEAL 1 and IDEAL 2) in pretreated non-small cell lung cancer reported a response rate approaching 20% in second-line patients and approximately 10% in those pretreated with two or more chemotherapy regimens. The median survival in these two studies approached 6-8 months. As a first-line therapy, gefitinib has been assessed in combination with two different chemotherapy regimens in two large randomized studies (INTACT 1 and INTACT 2). Both studies failed to show an improvement in survival on a total patient accrual of >1000 patients in each study. Other end points (e.g., time to progression and response rate) were also not improved by the addition of gefitinib. Additional studies are indicated to assess the possible role of gefitinib in the maintenance of patients who received chemotherapy or chemoradiotherapy. Studies investigating gefitinib as first-line monotherapy are also required.
Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy. [2019]Targeted therapies are one of the latest innovative trends in cancer therapy. The epidermal growth factor receptor (EGFR) is a target found in high concentrations in several solid tumors including lung, breast, colorectal, and brain. Tyrosine kinase inhibitors, such as gefitinib (Iressa, ZD1839), block the EGFR. As a result, there is inhibition of cellular proliferation, promotion of apoptosis, and inhibition of anti-angiogenesis. Gefitinib has demonstrated significant efficacy in non-small-cell lung cancer (NSCLC), leading to FDA approval for treatment of this refractory disease. Phase 2 trials with gefitinib for platinum refractory NSCLC reported disease response and symptom improvement. Early results of phase 2 studies of gefitinib, combined with standard chemotherapy in colorectal cancer, showed a 75% response rate compared with 55% with standard therapy alone. Gefitinib, combined with flutamide, produced an additive growth inhibition in prostate cancer. A phase 2 trial of gefitinib in first-relapse glioblastoma multiforme demonstrated median overall survival from treatment start of 39.4 weeks compared with 40 weeks with standard chemotherapy. Gefitinib is an oral agent with a mild toxicity profile, and thus, may be an optimal addition to chemotherapeutic regimens for some solid tumors. Gefitinib is potentially a vital and useful weapon in the arsenal of cancer therapies.
Gefitinib: current and future status in cancer therapy. [2018]The epidermal growth factor receptor (EGFR) is recognized as a key modulator of tumor cell function and is considered to be a viable drug target in a range of solid malignancies. Current knowledge of its role in tumor growth and progression has led to a newly active area of anticancer research, investigating agents that target the activity of this receptor. Of these agents, gefitinib is furthest in clinical development, having received regulatory approval in Japan in 2002, and in the United States and Australia in 2003. Gefitinib is an orally active, EGFR-tyrosine kinase inhibitor that blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and other host-dependent processes promoting cancer cell growth. A plethora of preclinical studies have suggested promising outcomes for this agent and have led to ongoing clinical trials in a wide range of tumors, including non-small-cell lung, head and neck, colorectal, prostate, and breast, either as monotherapy or in combination with standard chemotherapy, hormonal therapy, or radiotherapy. Furthermore, as biologic agents are specifically designed to attack different pathways of tumor growth and progression, the potential for the combination of gefitinib with other agents, given either concurrently or sequentially, to prevent or delay disease recurrence is also being investigated. This article provides a detailed overview of gefitinib, the rationale for its use in a wide range of tumor types, and the current clinical development status of this novel agent.
Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. [2023]Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours.
A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. [2022]The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors.
A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. [2021]Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is approved in the United States for the treatment of various B-cell malignancies. Preclinical data suggest synergistic antitumor activity of ibrutinib with programmed death-ligand 1 (PD-L1) inhibitors in solid tumors. This study evaluated ibrutinib plus durvalumab, a PD-L1-targeting antibody, in patients with relapsed/refractory solid tumors.
Neratinib, A Novel HER2-Targeted Tyrosine Kinase Inhibitor. [2019]HER2 gene amplification and receptor overexpression is identified in 20% to 25% of human breast cancers. Use of targeted therapy for HER2-amplified breast cancer has led to improvements in disease-free and overall survival in this subset of patients. Neratinib is an oral pan HER inhibitor, that irreversibly inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR or HER1), HER2, and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is currently being tested in a number of clinical trials for its safety and efficacy in lung cancer, and colorectal, bladder, and breast cancers. In this review we discuss the available phase I, II, and III data for use of neratinib in the metastatic, adjuvant, neoadjuvant, and extended adjuvant settings along with the ongoing clinical trials of neratinib in breast cancer. We also elaborate on the side effect profile of this relatively new drug and provide guidelines for its use in clinical practice.
Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study. [2023]Ibrutinib, a first-in-class inhibitor of Bruton's tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated.
A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. [2023]This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours.
Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors. [2022]This phase I study evaluated safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel.
A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer. [2021]PF-04691502 and gedatolisib (PF-05212384) are potent, dual PI3K/mTOR inhibitors. This phase II study (B1271004) was conducted in patients with recurrent endometrial cancer following platinum-containing chemotherapy. The primary endpoint was to assess clinical benefit response (complete or partial response, or stable disease for ≥16weeks) following treatment with PF-04691502 or gedatolisib.
Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer. [2023]Studies have demonstrated the efficacy of Palbociclib (CDK 4/6 inhibitor), Gedatolisib (PI3K/mTOR dual inhibitor) and PD0325901 (MEK1/2 inhibitor) in colorectal cancer (CRC), however single agent therapeutics are often limited by the development of resistance.