TRK-950 Combinations for Ovarian Cancer

Not currently recruiting at 13 trial locations

Overseen By Diane Parker

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Toray Industries, Inc

Must not be taking: Investigational agents

Disqualifiers: Cardiac disease, Infections, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and optimal dose of a new drug, TRK-950, in combination with other treatments for various advanced solid cancers. It includes groups for conditions such as ovarian, colorectal, and gastric cancer. Participants may qualify if they have specific cancer types, like ovarian cancer that has recurred after platinum-based treatment, or gastric cancer without prior treatment with certain drugs. The trial seeks participants who have progressed on previous treatments and meet specific cancer type and treatment history criteria. As a Phase 1 trial, the research aims to understand how TRK-950 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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, if your current medications are contraindicated (not recommended) with the trial treatments, you may need to stop them. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TRK-950, when combined with other treatments, is under study for its safety and effectiveness in treating various cancers. Studies involving TRK-950 with Gemcitabine and Carboplatin reported that the combination was generally safe, with only moderate side effects, indicating it was mostly well-tolerated.

For those considering the TRK-950 and Paclitaxel combination, research has examined similar setups. Paclitaxel has demonstrated safety comparable to other treatment combinations, meaning it does not cause more side effects than similar options.

Research also supports the safety of combining TRK-950 with Pegylated Liposomal Doxorubicin (PLD). Past studies with PLD and other drugs showed safety levels similar to standard treatments.

These findings offer reassurance about the safety of these combinations. However, this trial is in its early stages, focusing primarily on determining safety and dosage. While initial results are promising, further research is needed to fully understand the safety of these drug combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

TRK-950 is unique because it combines with various chemotherapy drugs like Gemcitabine, Carboplatin, Paclitaxel, and others to potentially enhance treatment for conditions like ovarian, colorectal, gastric, and renal cell carcinoma. Unlike standard chemotherapy, which often targets rapidly dividing cells non-specifically, TRK-950 might work by a novel mechanism that targets specific cancer pathways, potentially leading to more effective and precise cancer cell destruction. Researchers are excited because this targeted approach could reduce side effects and improve outcomes for patients with these cancers compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that TRK-950, when combined with other cancer treatments, holds promise by targeting several cancer pathways. In this trial, participants may receive TRK-950 with gemcitabine and carboplatin, which may improve the quality of life for ovarian cancer patients. These drugs together have shown moderate side effects and help relieve symptoms. Another arm of the trial involves TRK-950 with paclitaxel, which might extend patients' lives. Studies have shown an average time of 8.9 months before the cancer worsens. Additionally, TRK-950 combined with pegylated liposomal doxorubicin (PLD) is being tested for its effectiveness, offering another option for patients with hard-to-treat ovarian cancer. Overall, these combinations suggest that TRK-950 could aid in managing ovarian cancer by complementing existing treatments. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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

You are expected to live for at least 3 more months.

I have renal cell carcinoma and have never been treated with Bevacizumab.

I have gastric cancer and haven't been treated with Ramucirumab or any Taxane.

Exclusion Criteria

I have recently undergone treatment such as radiation, surgery, or chemotherapy.

I do not have an active HIV, hepatitis B, or hepatitis C infection.

Current treatment with any other investigational agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TRK-950 in combination with various anti-cancer regimens, administered in cycles of 21 or 28 days depending on the specific regimen

6-12 months

Multiple visits per cycle (in-person)

Maintenance

Participants transition to maintenance treatment with Bevacizumab after 6 cycles of chemotherapy, continued as long as there is no evidence of progressive disease

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-FU
• Bevacizumab
• Carboplatin
• Cisplatin
• Gemcitabine
• Imiquimod Cream
• Irinotecan
• Leucovorin
• Nivolumab
• Paclitaxel
• Pembrolizumab
• PLD
• Ramucirumab
• Topotecan
• TRK-950

Trial Overview

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.

How Is the Trial Designed?

Group I: Arm T: TRK-950 + Paclitaxel Experimental Treatment 2 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/ Bevacizumab Experimental Treatment 4 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 + Bevacizumab Experimental Treatment 2 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/Paclitaxel Experimental Treatment 3 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 + PLD Experimental Treatment 2 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 / Bevacizumab Experimental Treatment 4 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 + FOLFIRI Experimental Treatment 4 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 inhibitors Experimental Treatment 3 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 + Bevacizumab Experimental Treatment 2 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 Cream Experimental Treatment 2 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 inhibitors Experimental Treatment 3 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/Paclitaxel Experimental Treatment 3 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/Carboplatin Experimental Treatment 3 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/Cisplatin Experimental Treatment 3 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 + FOLFIRI Experimental Treatment 4 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.

Who Is Running the Clinical Trial?

Toray Industries, Inc

Lead Sponsor

Trials

22

Recruited

2,400+

Headquarters

Japan

Known For

Gene Therapies

Top Products

FERON™, DORNER™, REMITCH™

Published Research Related to This Trial

In a phase I trial involving 35 patients with recurrent platinum-sensitive ovarian cancer, the combination of ribociclib with carboplatin and paclitaxel chemotherapy was found to be safe, with a maximum tolerated dose of 400 mg.

The treatment showed a high overall response rate of 79.3% and a clinical benefit rate of 96.6%, with a median progression-free survival of 11.4 months, indicating promising initial efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. Coffman, LG., Orellana, TJ., Liu, T., et al.[2022]

Ovarian cancer is a leading cause of cancer-related deaths in women, and its poor survival rates are often due to recurrence after surgery and chemotherapy, highlighting the need for improved treatment strategies.

Recent advancements in targeted therapies, such as antiangiogenic agents and PARP inhibitors, along with ongoing research into combination treatments, show promise in enhancing clinical outcomes by simultaneously targeting multiple cancer pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategic Combination Therapies for Ovarian Cancer. Li, X., Ng, ASN., Mak, VCY., et al.[2021]

The combination of platinum and paclitaxel is effective for treating advanced ovarian cancer, but many patients eventually develop drug-resistant disease.

Topotecan, an FDA-approved treatment for recurrent ovarian cancer, can be used early to effectively prolong the time before patients need platinum-based treatments again, making it a valuable strategy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy. Bookman, MA.[2022]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

Despite high initial response rates to surgery and platinum-based chemotherapy in ovarian cancer, most patients experience relapse, highlighting the need for new treatment strategies to improve survival.

Recent phase III trials have shown that the anti-angiogenic agent bevacizumab, when used alongside chemotherapy and as maintenance therapy, can positively impact outcomes in first-line ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. Raja, FA., Chopra, N., Ledermann, JA.[2022]

Recent clinical research has focused on improving the effectiveness and reducing the side effects of systemic therapies for ovarian cancer using FDA-approved antineoplastic agents, including cisplatin and paclitaxel.

The study highlights the potential of both established and newly approved drugs for treating ovarian cancer, suggesting that ongoing research will continue to enhance treatment options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New, expanded, and modified use of approved antineoplastic agents in ovarian cancer. Markman, M.[2007]

The combination of carboplatin and adavosertib was found to be safe and effective in treating patients with TP53 mutated platinum-resistant ovarian cancer, showing an objective response rate of 41% among 29 evaluable patients.

Despite its efficacy, the treatment was associated with significant bone marrow toxicity, which was the most common reason for dose reductions and delays, highlighting a safety concern that needs to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. Embaby, A., Kutzera, J., Geenen, JJ., et al.[2023]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

Panobinostat, a histone deacetylase inhibitor, shows significant synergy with gemcitabine and paclitaxel, and particularly strong synergistic effects when combined with doxorubicin and carboplatin in treating metastatic ovarian cancer cell lines.

The study utilized in vitro assays on three ovarian cancer cell lines (SK-OV3, CaOV-3, and ES-2) to identify effective drug combinations, suggesting that these combinations could enhance treatment efficacy and warrant further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. Budman, DR., Tai, J., Calabro, A., et al.[2021]

Olaparib-resistant ovarian cancer cells showed higher proliferation rates and increased expression of P38 and JNK proteins, indicating these pathways are involved in resistance mechanisms.

Combining P38 and JUN inhibitors significantly reduced cell growth and migration in resistant ovarian cancer cells, demonstrating potential as a therapeutic strategy to overcome olaparib resistance, with confirmed anti-tumor effects in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell. Chen, X., Chen, Y., Lin, X., et al.[2018]

Research is focusing on non-cross-resistant drugs like oxaliplatin and topotecan for treating drug-resistant ovarian cancer, with many being tested in combination therapies to improve outcomes.

Innovative strategies such as anticancer vaccines and gene therapy are being explored, highlighting the importance of clinical trials for women with advanced ovarian cancer due to low current cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative therapies for advanced ovarian cancer. Trimble, EL.[2012]

Platinum-resistant ovarian cancer is a challenging disease with a poor prognosis, often characterized by low immune cell infiltration, leading to low response rates (less than 8%) to anti-PD1/PD-L1 therapies.

Emerging strategies to enhance treatment efficacy include combining immune checkpoint inhibitors with chemotherapy, anti-angiogenic agents, and other immunotherapies, with ongoing studies aiming to identify optimal combinations and predictive biomarkers for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. Le Saux, O., Ray-Coquard, I., Labidi-Galy, SI.[2022]

Recent advancements in ovarian cancer treatment include new therapies that combine chemotherapy with targeted agents like PARP inhibitors and immune checkpoint inhibitors, which are currently being tested in clinical trials.

Emerging treatments targeting specific pathways related to ovarian cancer growth, such as folate receptor α and various kinases, show promise and could significantly improve outcomes for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease. Arend, RC., Jackson-Fisher, A., Jacobs, IA., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03872947

A Study of TRK-950 in Combinations With Anti-Cancer ...

This study is an open-label, Phase 1b study evaluating TRK-950 in combination with 1) FOLFIRI or 2) Gemcitabine / Cisplatin or 3) Gemcitabine / Carboplatin or 4 ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/22659190/

A phase II clinical trial of pegylated liposomal doxorubicin ...

Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32305099/

a randomised, open-label, phase 3 trial

Interpretation: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer.

4.

bcan.org

bcan.org/clinicaltrials/a-study-of-trk-950-in-combinations-with-anti-cancer-treatment-regimens-in-patients-with-advanced-solid-tumors/

A Study of TRK-950 in Combinations With Anti-Cancer ...

The main purpose of this study is to establish the safety and the recommended dose of TRK-950 in combination with FOLFIRI, Gemcitabine / Cisplatin, Gemcitabine ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01097746

First-Line Treatment of Bevacizumab, Carboplatin, and ...

This phase II trial studies how well first-line treatment of bevacizumab, carboplatin, and paclitaxel work in treating participants with stage III- IV ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2019/125085s331lbl.pdf

Avastin - accessdata.fda.gov

The safety data in Warnings and Precautions and described below reflect exposure to Avastin in 4134 patients including those with mCRC (AVF2107g, E3200), non- ...

7.

go.drugbank.com

go.drugbank.com/conditions/DBCOND0030277

Primary Peritoneal Cancer (DBCOND0030277)

Associated Data ; NCT00085358. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00434642

NCT00434642 | A Study of Carboplatin and Gemcitabine ...

This is a placebo-controlled, randomized, multicenter Phase III study that will evaluate the safety and efficacy of bevacizumab, administered in combination ...