TRK-950 Combinations for Ovarian Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Toray Industries, Inc
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug, TRK-950, combined with other cancer treatments in patients with advanced cancers. The goal is to see if TRK-950 can help these treatments work better by boosting the body's ability to fight cancer or making cancer cells more vulnerable.
Is the drug TRK-950 a promising treatment for ovarian cancer?Yes, TRK-950 is a promising drug for ovarian cancer because it is part of new combination therapies that target multiple cancer pathways, potentially improving treatment outcomes.234910
What safety data is available for TRK-950 combinations in ovarian cancer treatment?The safety data for TRK-950 combinations in ovarian cancer treatment is not directly mentioned in the provided research abstracts. However, the abstracts discuss the safety and efficacy of various antineoplastic agents and combinations, such as platinum-based chemotherapy, paclitaxel, and bevacizumab, which are commonly used in ovarian cancer treatment. For example, a Phase I trial combining ribociclib with carboplatin and paclitaxel reported common adverse events like anemia, neutropenia, fatigue, and nausea, indicating the safety profile of such combinations. Additionally, the use of bevacizumab in combination with chemotherapy has shown a positive effect in large phase III trials. These findings suggest that while specific safety data for TRK-950 is not detailed, the safety of similar combination therapies has been evaluated in clinical settings.3571112
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 participate if you are currently receiving any other investigational agent or if your medications are contraindicated with the trial's treatment regimens. It's best to discuss your specific medications with the trial team.
What data supports the idea that TRK-950 Combinations for Ovarian Cancer is an effective treatment?The available research does not provide specific data on the effectiveness of TRK-950 Combinations for Ovarian Cancer. However, it highlights the importance of combination therapies in treating ovarian cancer, which target multiple cancer pathways to improve outcomes. Other studies mention the effectiveness of different drug combinations, such as carboplatin with adavosertib for certain ovarian cancer types, and the synergy of panobinostat with other drugs in cell lines. These findings suggest that combining different treatments can be beneficial, but specific data on TRK-950 is not provided.168913
Eligibility Criteria
This trial is for adults with various advanced solid tumors, including specific types of ovarian, colorectal, and renal cancers. Participants must have measurable tumors and meet criteria for certain treatment regimens based on their cancer type and previous treatments. Pregnant women or those with recent therapies or serious infections are excluded.Inclusion Criteria
I have renal cell carcinoma and have never been treated with Bevacizumab.
I have ovarian, peritoneal, or fallopian tube cancer, treated with platinum less than 3 times and it returned more than 6 months after the last treatment.
My cancer type and history require specific treatments.
I am 18 years old or older.
I am able to care for myself but may not be able to do active work.
My tumor can be measured using scans or special tools.
I have colorectal cancer and have never been treated with Irinotecan or FOLFIRI.
I have cholangiocarcinoma or bladder cancer and haven't been treated with Gemcitabine.
Exclusion Criteria
I do not have an active HIV, hepatitis B, or hepatitis C infection.
I do not have any health conditions or take any medications that would prevent me from receiving the treatment.
My lab values do not prevent me from receiving standard cancer treatments.
I do not have a serious illness that could interfere with the study.
I do not have any serious infections needing treatment.
I have severe heart issues, recent heart attack, or unstable heart rhythm.
Treatment Details
The study tests the safety and optimal dose of TRK-950 in combination with other cancer drugs like FOLFIRI, Gemcitabine/Cisplatin, Ramucirumab/Paclitaxel, PD1 inhibitors (Nivolumab or Pembrolizumab), among others. It aims to find effective treatments tailored to different tumor types.
15Treatment groups
Experimental Treatment
Group I: Arm T: TRK-950 + PaclitaxelExperimental Treatment2 Interventions
* Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On days 1, 8 and 15 of each cycle, Paclitaxel will be dosed on IV
Group II: Arm S: TRK-950 + Carboplatin / PLD/ BevacizumabExperimental Treatment4 Interventions
* Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer
* Treatment Phase: TRK-950 will be administered IV on days 1 and 15 of a 28-day cycle. Carboplatin will be administered as an intravenous infusion on day 1. On day 1, following the administration of Carboplatin, PLD will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next.
On days 1 and 15, TRK-950 will be administered IV after the Bevacizumab infusion.
• Maintenance Phase: After 6 cycles of chemotherapy, the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Following the Bevacizumab administration, TRK-950 will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease.
Group III: Arm R: TRK-950 + BevacizumabExperimental Treatment2 Interventions
* Renal cell carcinoma cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. Bevacizumab will be dosed as IV on Day 1 and 15 of each cycle. On days that TRK-950 and Bevacizumab are both dosed, Bevacizumab will be dosed first.
Group IV: Arm Q: TRK-950 + Ramucirumab/PaclitaxelExperimental Treatment3 Interventions
* Gastric cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. On days 1 and 15, ramucirumab will be administered IV. Paclitaxel will be dosed on days 1, 8 and 15, after ramucirumab on days 1 and 15, before TRK-950 on day 8.
Group V: Arm O: TRK-950 + PLDExperimental Treatment2 Interventions
* Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. PLD will be dosed as IV on Day 1 of each cycle. On days that TRK-950 and PLD are both dosed, PLD will be dosed first.
Group VI: Arm K: TRK-950 + Gemcitabine / Carboplatin / BevacizumabExperimental Treatment4 Interventions
* Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer
* TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. Gemcitabine will be administered as an intravenous infusion on days 1 and 8. On day 1, following the administration of Gemcitabine, Carboplatin will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. After 6 cycles of chemotherapy the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease.
Group VII: Arm J: TRK-950 + FOLFIRIExperimental Treatment4 Interventions
* Colorectal Cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion.
Group VIII: Arm H: TRK-950 + PD1 inhibitorsExperimental Treatment3 Interventions
•Melanoma
H-1: TRK-950 + Nivolumab
•TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion.
H-2: TRK-950 + Pembrolizumab
•TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion.
Group IX: Arm G: TRK-950 + BevacizumabExperimental Treatment2 Interventions
* Renal Cell Carcinoma
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Bevacizumab will be administered as an IV infusion.
Group X: Arm F: TRK-950 + Imiquimod CreamExperimental Treatment2 Interventions
* Palpable subcutaneous malignant lesions
* TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. Imiquimod cream is to be applied 5 of 7 days in a row with 2 days rest for a maximum of 2 cycles (total 6 weeks).
Group XI: Arm E: TRK-950 + PD1 inhibitorsExperimental Treatment3 Interventions
•Solid Tumors
E-1: TRK-950 + Nivolumab
•TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion.
E-2: TRK-950 + Pembrolizumab
•TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion.
Group XII: Arm D: TRK-950 + Ramucirumab/PaclitaxelExperimental Treatment3 Interventions
* Gastric Cancer
* TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Ramucirumab will be administered as an IV infusion. Paclitaxel will be dosed on days 1, 8 and 15, after the Ramucirumab on days 1 and 15 and after the TRK-950 on day 8.
Group XIII: Arm C: TRK-950 + Gemcitabine/CarboplatinExperimental Treatment3 Interventions
* Ovarian Cancer
* TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Gemcitabine will be administered as an intravenous infusion. On day 1, following the administration of TRK-950 and Gemcitabine, Carboplatin will be administered IV.
Group XIV: Arm B: TRK-950 + Gemcitabine/CisplatinExperimental Treatment3 Interventions
* Cholangiocarcinoma or Bladder Cancer
* TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Cisplatin will be administered by infusion. Then, Gemcitabine will be administered as an IV infusion.
Group XV: Arm A: TRK-950 + FOLFIRIExperimental Treatment4 Interventions
* Colorectal Cancer
* TRK-950 will be administered intravenously (IV) on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Perlmutter Cancer Center at NYU LangoneNew York, NY
AOA-HOPETucson, AZ
Texas Oncology, P.A. Baylor Charles A. Sammons Cancer CenterDallas, TX
HOAG Memorial Hospital PresbyterianNewport, CA
More Trial Locations
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Who is running the clinical trial?
Toray Industries, IncLead Sponsor
References
Treatment of refractory and recurrent ovarian cancer. [2005]Patients with recurrent ovarian cancer can be divided into two groups: those who have recurrence more than 6 months after primary therapy with paclitaxel/platinum (ie, platinum-sensitive) and those with tumor progression or recurrence within 6 months of primary therapy (ie, platinum-resistant). In patients with platinum-sensitive tumors and good performance status, re-treatment with paclitaxel/platinum combination therapy is usually the most appropriate choice. For patients with minimum residual disease, the greatest promise for long-term disease-free survival is associated with intensive intraperitoneal therapy with combinations of cisplatin and intravenous/intraperitoneal paclitaxel. Alternatively, patients with platinum-sensitive disease can receive intravenous carboplatin or paclitaxel. Patients with platinum-resistant ovarian cancer can benefit from single-agent therapy with altretamine, topotecan, oral etoposide, ifosfamide, liposomal doxorubicin, or other standard or investigational regimens. (Of these drugs, only altretamine and topotecan are approved by the US Food and Drug Administration for persistent or recurrent ovarian cancer.) Since the response rates achieved with these drugs are similar, patient convenience, side effects, and cost may play a significant role in drug selection.
Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy. [2022]Although the combination of platinum and paclitaxel offers effective chemotherapy for advanced ovarian cancer, the majority of women will eventually relapse with development of drug-resistant disease. Topotecan is the most extensively studied agent currently available for management of recurrent ovarian cancer and has been approved by the FDA for that particular indication. Early use of topotecan offers an effective and tolerable strategy that can prolong the platinum-free interval and optimize subsequent retreatment with platinum.
Innovative therapies for advanced ovarian cancer. [2012]The emergence of drug-resistant tumors during therapy for ovarian cancer remains an obstacle to improving long-term outcomes. Active areas of ovarian cancer research include clinical evaluation of non-cross-resistant antineoplastic agents that demonstrated single-agent activity in ovarian cancer during the 1990s: oxaliplatin, the new anthracyclines (epirubicin, liposomal doxorubicin), topotecan, oral etoposide, gemcitabine, and vinorelbine. Most of these new agents are currently being evaluated as a component of doublet and triplet combination regimens for advanced ovarian cancer, with use of sequential alternating doublet regimens gaining interest. The potential role of intraperitoneal therapy continues to be investigated. In addition, there are a variety of innovative treatment strategies on the horizon that are targeted at underlying disease processes, including anticancer vaccines, gene therapy, and antiangiogenic therapy. Based on this multitude of investigational questions and the low cure rates currently achieved, all women with advanced ovarian cancer should be offered participation in clinical trials.
[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]The standard primary therapy of advanced ovarian cancer consists of platinum derivatives in combination with paclitaxel. In a first report presented at this year's meeting of the American Society of Clinical Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in combination with carboplatin, while the toxicity profile present some advantages. The addition of a third drug to platinum-taxane-combination does not appear to improve the therapeutic index. According to the data of the ICON1- and ACTION-trial, carboplatin containing chemotherapies are associated with a significant benefit also in early ovarian cancer. Platinum-resistant disease remains a therapeutic challenge, since the available drugs display only limited activity of short duration. Some experimental data suggest evidence for a possible therapeutic role of small molecules that inhibit the epidermal growth factor receptor (OSI-774) or antisense oligonucleotides interfering with EGF-receptor signalling (ISIS 5132). Novel classes of chemotherapeutic agents, including the acylfulvenes and the epothilone-analogues warrant further study in this disease. Multimodal therapies combining cytotoxic agents with antibodies against CA 12-5 or metalloproteinase inhibitors have failed to demonstrate any survival benefit in patients with ovarian cancer. Despite significant progress in the last decade ovarian cancer remains the most lethal gynaecologic malignancy in women in most western countries. Further multicenter clinical studies are needed to better define new therapeutic options.
New, expanded, and modified use of approved antineoplastic agents in ovarian cancer. [2007]Over the past several years, clinical research efforts in ovarian cancer employing a number of U.S. Food and Drug Administration (FDA)-approved antineoplastic agents have permitted the development of approaches that both improve the effectiveness and decrease the toxicities of systemic therapy of ovarian cancer. These initiatives, including prospective trials and retrospective examinations of large clinical experience, have involved agents previously approved by the FDA for use in ovarian cancer (e.g., cisplatin, paclitaxel, topotecan, and liposomal doxorubicin) and the development of new strategies for drugs approved for other malignant conditions (e.g., gemcitabine, docetaxel, etoposide, irinotecan, vinorelbine, and bevacizumab). It can be anticipated that future studies involving novel approved agents will further expand the oncologist's weapons against ovarian cancer.
The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. [2021]Although platinum based therapy has improved short term survival of patients with metastatic ovarian cancer, the majority of patients continue to relapse and eventually die of their disease. Currently, a plethora of agents are in development, but how to combine them to enhance efficacy remains largely empiric. We have used short in vitro culture of defined cell lines with application of promising agents and analysis for cell death using a MTT assay to identify potentially useful combinations. Using median effect analysis, curve shift analysis and apoptosis assays, we can identify when agents are synergistic or antagonistic when applied together. Up to three agents can be studied in combination. Using three cell lines: SK-OV3, CaOV-3, and ES-2 (a clear cell tumor), we have identified that panobinostat (LBH-589), a broad histone deacetylase inhibitor in clinical trials, demonstrates global synergy with gemcitabine, with paclitaxel, and additive to synergistic effects with 5'DFUR. The triplet of panobinostat, doxorubicin, and carboplatin is especially synergistic in these cell lines. These effects are cytotoxic and not cytostatic. As all these agents are used clinically, we have identified combinations which warrant further investigation.
Optimal first-line treatment in ovarian cancer. [2022]Treatment of ovarian cancer remains challenging despite the high complete response rate seen after maximal surgical debulking surgery and platinum-combination chemotherapy. as most patients will relapse and eventually succumb to ovarian cancer, new strategies are urgently required to improve survival. a platinum-taxane combination has been the cornerstone of treatment for >15 years. Better use of these drugs is being explored through scheduling studies, and dose-dense or intraperitoneal (IP) therapies. Further improvements in treatment will most likely come from the integration of optimal chemotherapy with one or more of the hundreds of molecular-targeted agents that could be active in ovarian cancer. The greatest experience has been with anti-angiogenic agents. Two large phase III trials in first-line ovarian cancer have demonstrated a positive effect of bevacizumab when administered concurrently with chemotherapy and then as a maintenance treatment. In this review, we discuss the existing treatments for ovarian cancer and highlight areas of recent progress.
The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell. [2018]Many targeted ovarian cancer patients are resistant to olaparib treatment. Here we seek to understand the underlying molecular events and search for potential combinational therapeutics to surmount the intrinsic olaparib resistance in human ovarian cancer.
Strategic Combination Therapies for Ovarian Cancer. [2021]Ovarian cancer remains the leading cause of gynecologic cancer-related deaths among women worldwide. The dismal survival rate is partially due to recurrence after standardized debulking surgery and first-line chemotherapy. In recent years, targeted therapies, including antiangiogenic agents or poly (ADP-ribose) polymerase inhibitors, represent breakthroughs in the treatment of ovarian cancer. As more therapeutic agents become available supplemented by a deeper understanding of ovarian cancer biology, a range of combination treatment approaches are being actively investigated to further improve the clinical outcomes of the disease. These combinations, which involve DNA-damaging agents, targeted therapies of signaling pathways and immunotherapies, simultaneously target multiple cancer pathways or hallmarks to induce additive or synergistic antitumor activities. Here we review the preclinical data and ongoing clinical trials for developing effective combination therapies in treating ovarian cancer. These emerging therapeutic modalities may reshape the treatment landscape of the disease.
Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. [2022]Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.
Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease. [2023]Recently approved therapies have contributed to a significant progress in the management of ovarian cancer; yet, more options are needed to further improve outcomes in patients with advanced disease. Here we review the rationale and ongoing clinical trials of novel combination strategies involving chemotherapy, poly ADP ribose polymerase, programmed death 1 (PD-1)/PD-ligand 1 immune checkpoint and/or vascular endothelial growth factor receptor inhibitors. Further, we discuss novel agents aimed at targets associated with ovarian cancer growth or progression that are emerging as potential new treatment approaches. Among them, agents targeted to folate receptor α, tissue factor, and protein kinase-mediated pathways (WEE1 kinase, phosphatidylinositol-3 kinase α, cell cycle checkpoint kinase 1/2, ATR kinase) are currently in clinical development as mono- or combination therapies. If successful, findings from these extensive development efforts may further transform treatment of patients with advanced ovarian cancer.
Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. [2022]BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.METHODSThis phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib, followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).RESULTSThirty-five patients were enrolled. Patients had a mean of 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab. The MTD was 400 mg. The most common adverse events included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). The overall RR was 79.3%, with a stable disease rate of 18%, resulting in a clinical benefit rate of 96.6%. Median PFS was 11.4 months. RR and PFS did not differ based on the number of lines of prior chemotherapy or prior maintenance therapy.CONCLUSIONThis work demonstrates that the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03056833.FUNDINGThis investigator-initiated trial was supported by Novartis, which provided drugs and funds for trial execution.
WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. [2023]In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response to this combination treatment.