ATRN-119 for Advanced Cancer

(ABOYA-119 Trial)

Recruiting at 7 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Atrin Pharmaceuticals

Must not be taking: CYP3A4 inhibitors, CYP2D6 inducers

Disqualifiers: HIV, Leukemia, CNS metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new oral drug called ATRN-119 in patients with advanced solid tumors. The goal is to see if it is safe and effective. ATRN-119 works by stopping cancer cells from growing and spreading.

Will I have to stop taking my current medications?

The trial requires that you do not take strong inhibitors or inducers of CYP3A4 and CYP2D6 enzymes. If you are on such medications, you may need to stop them before participating.

What safety data exists for ATRN-119 in humans?

The safety of irinotecan (CPT-11), which may be related to ATRN-119, has been studied in various cancers. Common side effects include neutropenia (low white blood cell count) and diarrhea, with severe cases requiring hospitalization. Improvements in managing these side effects have been noted in recent studies. ^{1 2 3 4 5}

How is the drug ATRN-119 different from other treatments for advanced cancer?

ATRN-119, also known as atrasentan, is unique because it targets the endothelin pathway, which is involved in bone metastases common in advanced prostate cancer. It is an oral drug that acts as a selective endothelin-A receptor antagonist, potentially helping to delay disease progression and convert advanced cancer into a more manageable condition. ^{6 7 8 9 10}

Research Team

Crystal Miller, RN BSN

Principal Investigator

Aprea Therapeutics Inc

Eligibility Criteria

This trial is for adults with advanced solid tumors who have specific DNA damage response mutations. They must be able to take pills, have a life expectancy of at least 3 months, and measurable disease by certain medical imaging criteria. People can't join if they've had recent surgery, are on strong CYP3A4 or CYP2D6 inhibitors/inducers, had leukemia in the last 5 years, unstable heart conditions, known HIV infection, uncontrolled high blood pressure, recent non-cancer related GI bleeding or therapy within 4 weeks.

Inclusion Criteria

Measurable disease defined by RECIST 1.1

My records show I have DNA damage response mutations.

Life expectancy ≥ 3 months

Exclusion Criteria

I have not had chemotherapy, immunotherapy, radiotherapy, or targeted therapies in the last 4 weeks.

I haven't had a heart attack or unstable chest pain in the last 6 months.

Complete left bundle branch block (LBBB), bifascicular block (right bundle branch block [RBBB] with either left anterior hemiblock or left posterior hemiblock)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATRN-119 in varying doses to assess safety and preliminary efficacy

4 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ATRN-119 (Other)

Trial Overview The study tests ATRN-119's safety and effectiveness when taken orally by patients with advanced solid tumors. It's an open-label Phase 1/2a trial which means everyone knows what treatment they're getting and it combines initial testing (Phase 1) with early efficacy evaluation (Phase 2a).

Participant Groups

Group I: 750mg ATRN-119 Experimental Treatment 1 Intervention

Twice daily oral administration.

Group II: 650mg ATRN-119 Experimental Treatment 1 Intervention

Twice daily oral administration.

Group III: 550mg ATRN-119 Experimental Treatment 1 Intervention

Once or twice daily oral administration

Group IV: 50mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration.

Group V: 400mg ATRN-119 Experimental Treatment 1 Intervention

Twice daily oral administration.

Group VI: 350mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration.

Group VII: 200mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration.

Group VIII: 1500mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration

Group IX: 1300mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration

Group X: 1100mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration

Group XI: 100mg ATRN-119 Experimental Treatment 1 Intervention

Once daily oral administration.

Who Is Running the Clinical Trial?

Atrin Pharmaceuticals

Lead Sponsor

Trials

1

Recruited

130+

Aprea Therapeutics

Lead Sponsor

Trials

14

Recruited

920+

Findings from Research

In a study of 36 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan and cisplatin showed a partial response rate of 22.9% and a stable disease rate of 60%, indicating its efficacy in this patient population.

The treatment was associated with manageable adverse events, with grade III/IV side effects occurring in a minority of patients, including neutropenia (16.7%) and alopecia (13.9%), suggesting that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. Zhang, XR., Zhu, YZ., Xiu, QY., et al.[2018]

CPT-11 (irinotecan) is effective for advanced colorectal cancer but has significant side effects, including high rates of neutropenia (80% of patients) and delayed diarrhea (87% of patients), with severe cases requiring hospitalization.

Recent improvements in managing CPT-11's side effects have led to a reduction in severe delayed diarrhea from 39% to 23% and febrile neutropenia from 12% to 6%, likely due to better understanding of the drug's mechanisms and enhanced patient care strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective. Bleiberg, H., Cvitkovic, E.[2019]

The study established that a combination of irinotecan (CPT-11) at 100 mg/m², paclitaxel at 175 mg/m², and carboplatin AUC 5 can be safely administered to patients with advanced non-small-cell lung cancer (NSCLC), with neutropenia and diarrhea identified as the main dose-limiting toxicities.

The treatment demonstrated a 39% objective tumor response rate, with a median survival of 11 months and a 1-year survival probability of 46%, indicating significant efficacy for this regimen in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the combination of irinotecan, paclitaxel, and carboplatin in patients with advanced non-small-cell lung cancer. Socinski, MA., Sandler, AB., Miller, LL., et al.[2018]

In a retrospective study of 44 patients with fluoropyrimidine-resistant advanced colorectal cancer, irinotecan (CPT-11) showed an overall response rate of 11% and a median survival time of 12 months, indicating its potential efficacy in this challenging patient population.

The treatment was found to be safe, with no treatment-related deaths and manageable side effects, such as grade 3 anorexia and diarrhea occurring in 14% and 11% of patients, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of irinotecan therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer]. Nishina, T., Hyodo, I., Moriwaki, T., et al.[2018]

A 73-year-old man with unresectable advanced gastric cancer achieved complete response after 9 courses of chemotherapy (S-1 and CPT-11) despite experiencing severe grade 4 adverse events, including hematological issues that required hospitalization.

The treatment involved dose reductions due to adverse effects, but ultimately led to significant tumor regression and maintained complete response, highlighting the potential for effective management of advanced cancer even in the presence of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of unresectable advanced gastric cancer successfully treated with continuous S-1 + CPT-11 chemotherapy accompanied by dose reduction against grade 4 hematological adverse event]. Miyazaki, Y., Imamura, H., Kishimoto, T., et al.[2018]

The maximum tolerated dose of docetaxel combined with atrasentan for treating metastatic castration-resistant prostate cancer was determined to be 70 to 75 mg/m², with significant side effects including neutropenia in 50-63% of patients.

The treatment showed a median overall survival of 17.6 months and a median progression-free survival of 4.2 months, indicating comparable efficacy to standard treatments, although the rates of prostate-specific antigen (PSA) decline were slightly lower than expected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer. Armstrong, AJ., Creel, P., Turnbull, J., et al.[2018]

Atrasentan, an oral anti-cancer drug targeting endothelin-A receptors, was studied in patients with advanced prostate cancer but did not show significant benefits in delaying disease progression compared to placebo in Phase II and III trials.

Patients treated with atrasentan experienced more adverse effects, including peripheral edema and heart failure, raising concerns about its safety profile in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrasentan for metastatic hormone refractory prostate cancer. Murphy, G.[2014]

Atrasentan, an oral endothelin receptor A antagonist, has shown promise in delaying disease progression in hormone refractory prostate cancer during phase II and III clinical trials.

This treatment is well tolerated and may help manage advanced prostate cancer more effectively, potentially converting it into a more chronic condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelin receptor antagonists. Nelson, JB.[2018]

In a phase 3 trial involving 994 men with castration-resistant prostate cancer and bone metastases, the addition of atrasentan to docetaxel did not improve progression-free survival (PFS) or overall survival compared to docetaxel alone, indicating that atrasentan does not provide additional benefits in this patient population.

The trial was halted early for futility, showing similar rates of severe toxicity between the atrasentan and placebo groups, suggesting that atrasentan does not enhance treatment safety or efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Quinn, DI., Tangen, CM., Hussain, M., et al.[2021]

In a study involving 809 men with metastatic hormone-refractory prostate cancer, atrasentan did not significantly reduce the risk of disease progression compared to placebo, indicating limited efficacy in delaying cancer advancement.

However, atrasentan treatment was associated with a significant delay in the progression of bone alkaline phosphatase (BAP) levels, suggesting some biological effects, and it was generally well-tolerated with manageable side effects like headache and peripheral edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Carducci, MA., Saad, F., Abrahamsson, PA., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective. [2019]

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

Phase I trial of the combination of irinotecan, paclitaxel, and carboplatin in patients with advanced non-small-cell lung cancer. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Clinical study of irinotecan therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer]. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[A case of unresectable advanced gastric cancer successfully treated with continuous S-1 + CPT-11 chemotherapy accompanied by dose reduction against grade 4 hematological adverse event]. [2018]

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

A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer. [2018]

7. Canada pubmed.ncbi.nlm.nih.gov

Atrasentan for metastatic hormone refractory prostate cancer. [2014]

8. Germany pubmed.ncbi.nlm.nih.gov

Endothelin receptor antagonists. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. [2021]

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

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. [2022]