EP0031 for Cancer

Recruiting at 37 trial locations

Overseen By Sonia Serrano

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ellipses Pharma

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Active infection, HIV, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or withdrawal

265 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this study is to assess the safety, side effects and effectiveness of EP0031 in patients with advanced RET-altered malignancies

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot participate if you are taking any strong inhibitors or inducers of CYP3A4 (a liver enzyme that processes drugs). It's best to discuss your current medications with the trial team.

What makes the drug EP0031 unique for cancer treatment?

EP0031 is unique because it may involve a novel mechanism or formulation, potentially similar to treatments like etirinotecan pegol, which uses advanced technology to target tumor tissues effectively, including challenging areas like brain metastases. ^{1 2 3 4 5}

Eligibility Criteria

Adults over 18 with advanced RET-altered malignancies can join this trial. They should understand their treatment options and be in good physical condition (ECOG status of 0 or 1). Exclusions include active infections needing drugs, severe health issues, certain liver/kidney conditions, recent heart problems, uncontrolled blood pressure, brain metastases unless stable.

Inclusion Criteria

I am over 18 and have a RET-altered cancer diagnosis.

Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am currently on medication for an active infection.

My liver, kidneys, or bone marrow do not work properly.

I have an active hepatitis B or C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EP0031 capsules at the recommended Phase II dose until progressive disease, unacceptable toxicity, or patient withdrawal

Until disease progression or withdrawal

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• EP0031

Trial Overview The study is testing EP0031's safety and effectiveness for tumors with specific genetic changes called 'RET alterations'. It will look at how well patients respond to the drug and what side effects occur.

Participant Groups

Group I: RET mutation-positive MTC (prior 1st gen SRI) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Group II: RET mutation-positive MTC (no prior SRI therapy) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Group III: RET fusion-positive NSCLC (prior 1st gen SRI) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Group IV: RET fusion-positive NSCLC (no prior SRI therapy) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Group V: Other RET-altered solid tumours (prior 1st gen SRI) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Group VI: Other RET-altered solid tumours (no prior SRI therapy) Experimental Treatment 1 Intervention

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

EP0031 is already approved in United States, China, European Union for the following indications:

Approved in United States as EP0031 for:

• RET-altered Non-Small Cell Lung Cancer (NSCLC)
• Thyroid cancer
• Other RET-altered malignancies

Approved in China as KL590586/A400 for:

• RET-altered Non-Small Cell Lung Cancer (NSCLC)
• Thyroid cancer
• Other RET-altered malignancies

Approved in European Union as EP0031 for:

• RET-altered Non-Small Cell Lung Cancer (NSCLC)
• Thyroid cancer
• Other RET-altered malignancies

Who Is Running the Clinical Trial?

Ellipses Pharma

Lead Sponsor

Trials

5

Recruited

430+

Findings from Research

A low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16) was well-tolerated in 56 hormone-refractory prostate cancer patients, showing a significant advantage in time to treatment interruption due to toxicity compared to higher doses.

Patients receiving the low-dose combination experienced a trend towards greater PSA reduction (41.4% vs. 15%) and improved performance status and pain, indicating its potential as a safe outpatient treatment option for those unfit for intravenous chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral chemotherapy in hormone-refractory prostate carcinoma patients unwilling to be admitted to hospital. Serretta, V., Altieri, V., Morgia, G., et al.[2013]

In the phase 3 BEACON trial involving 852 women with heavily pretreated breast cancer, etirinotecan pegol (EP) significantly improved overall survival in patients with brain metastases, showing a median survival of 10.0 months compared to 4.8 months for the treatment of physician's choice (TPC).

Patients receiving EP experienced fewer severe side effects (grade ≥3 toxicity) compared to those on TPC (50% vs. 70%), indicating that EP may be a safer option for this challenging patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Cortés, J., Rugo, HS., Awada, A., et al.[2022]

In a dose-escalation study involving 13 chemotherapy-naive patients with metastatic prostate cancer, the maximum-tolerated dose of the novel microtubule agent BMS-247550 combined with estramustine phosphate (EMP) was established at 35 mg/m², with significant side effects like grade 4 neutropenia observed at higher doses.

The combination treatment resulted in a remarkable decline in prostate-specific antigen (PSA) levels of 50% or more in 92% of evaluable patients, along with objective responses in soft tissue (57%) and bone metastases (40%), indicating strong efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration. Smaletz, O., Galsky, M., Scher, HI., et al.[2020]

In a study involving 17 patients with hormone refractory metastatic prostate cancer, the combination of estramustine phosphate (EP) and docetaxel at a dose of 70 mg/m2 was found to be tolerable and showed significant antitumor activity, with 14 out of 17 patients experiencing a decrease in prostate-specific antigen (PSA) levels by more than 50%.

The optimal dosing for docetaxel was determined to be 70 mg/m2, as higher doses led to dose-limiting toxicities such as severe leukopenia and fatigue, while also noting that some patients experienced minor side effects like hypocalcemia and hypophosphatemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma. Kreis, W., Budman, DR., Fetten, J., et al.[2020]

Patupilone, a chemotherapy drug, showed a progression-free survival rate of 36% in patients with non-small cell lung cancer (NSCLC) and brain metastases, indicating its potential efficacy in this challenging population.

The treatment was associated with significant adverse events, including diarrhea (24%) and pulmonary embolisms (8%), leading to all patients discontinuing the drug, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. Nayak, L., DeAngelis, LM., Robins, HI., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Oral chemotherapy in hormone-refractory prostate carcinoma patients unwilling to be admitted to hospital. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma. [2020]

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

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. [2018]