TRK-950 Combinations for Ovarian Cancer

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

187 Participants Needed

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.

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.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination TRK-950 for ovarian cancer?

Research shows that combining different drugs can improve treatment outcomes for ovarian cancer. For example, carboplatin and paclitaxel are often used together for platinum-sensitive ovarian cancer, and combinations like panobinostat with gemcitabine or paclitaxel have shown promising results in cell studies. These findings suggest that using multiple drugs together, like in the TRK-950 combination, may enhance effectiveness. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

What safety data exists for TRK-950 and related treatments in ovarian cancer?

The combination of ribociclib with platinum-based chemotherapy, including drugs like carboplatin and paclitaxel, was found to be safe in a study with common side effects such as anemia (low red blood cell count), neutropenia (low white blood cell count), fatigue, and nausea. Bevacizumab, another related treatment, has shown a positive effect when used with chemotherapy in ovarian cancer. ^{6 7 8 9 10}

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. ^{5 6 11 12 13}

What makes the drug TRK-950 unique for treating ovarian cancer?

TRK-950 is unique because it is part of a new wave of combination therapies that target multiple cancer pathways simultaneously, potentially offering more effective treatment by inducing stronger antitumor activities compared to traditional single-agent therapies. ^{5 6 11 12 13}

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

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

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

Treatment Details

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.

Participant Groups

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™

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. [2023]

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

Treatment of refractory and recurrent ovarian cancer. [2005]

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

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Strategic Combination Therapies for Ovarian Cancer. [2021]

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

Innovative therapies for advanced ovarian cancer. [2012]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. [2022]

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

Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

13. England pubmed.ncbi.nlm.nih.gov

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