NDI-219216 for Cancer

Recruiting at 10 trial locations

Overseen By Katie Ard, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nimbus Wadjet, Inc.

Disqualifiers: Cardiovascular disease, WRN syndrome, pregnancy, others

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

Compensation: Varies

Number of Visits: 6

134 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if NDI-219216 is safe for patients, and if NDI-219216 might be a possible treatment for advanced solid tumors in the later phases of the study. The main questions it aims to answer are: Is NDI-219216 safe and what kinds of side effects might it cause? What kind of effects does NDI-219216 have on the body? Does NDI-219216 have any impact on tumor size? Participants will: Take NDI-219216 every day by mouth. Visit the clinic 6 times during Cycle 1, 2 times during Cycle 2, once a month thereafter for checkups and tests while on the study, then one time for an end of treatment visit. After the End of Study, a follow up will occur but can be done on the phone. Keep a diary of their tablet consumption and symptoms experienced.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug NDI-219216 for cancer?

Cediranib, a component of NDI-219216, has shown effectiveness in inhibiting tumor growth by blocking VEGF (a protein that helps tumors grow blood vessels) in various cancers, including colorectal and lung cancer, as seen in multiple studies. ^{1 2 3 4 5}

Research Team

Anita Scheuber, MD, PhD

Principal Investigator

Nimbus Therapeutics, Inc.

Eligibility Criteria

This trial is for patients with advanced solid tumors, particularly those showing microsatellite instability. Participants must be able to take oral medication daily and commit to regular clinic visits for checkups and tests.

Inclusion Criteria

My cancer cannot be removed by surgery and has not responded to or I cannot tolerate standard treatments.

I am fully active or can carry out light work.

Presence of measurable disease according to RECIST version 1.1 except for Part A (Dose Escalation)

Exclusion Criteria

I have a serious heart condition.

I have been diagnosed with Werner syndrome.

Pregnancy, breastfeeding, or intention of becoming pregnant during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part A Dose Escalation

Participants receive increasing doses of NDI-219216 daily in 28-day treatment cycles. Dose Limiting Toxicity review period is 21 days for each cohort.

Up to 11-12 months

6 visits during Cycle 1, 2 visits during Cycle 2, monthly thereafter

Treatment - Part B Project Optimus

Participants are randomized between up to 3 dose levels determined from Part A, administered daily in 28-day treatment cycles.

Up to 18 months

Treatment - Part C Dose Expansion

Participants with dMMR/MSI-h status receive the optimal dose identified from Part B, administered daily in 28-day treatment cycles.

Up to 17 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up can be done on the phone.

30 days after last dose

Treatment Details

Interventions

• NDI-219216

Trial Overview The study is testing the safety and effectiveness of a new treatment called NDI-219216. Patients will take it orally every day, aiming to see if it's safe, its side effects, how it affects the body, and whether it can reduce tumor size.

Participant Groups

Group I: Part C Dose Expansion Experimental Treatment 1 Intervention

Part C will enroll 2 groups of patients with dMMR/MSI-h status and other select criteria, utilizing the optimal dose identified from Part B. NDI-219216 will be administered daily in 28-day repeating cycles.

Group II: Part B Project Optimus Experimental Treatment 1 Intervention

Part B will enroll up to 3 cohorts of patients randomized between up to 3 dose levels determined from Part A Dose Escalation. NDI-219216 will be administered daily in repeating 28-day treatment cycles.

Group III: Part A dose escalation Experimental Treatment 1 Intervention

Part A Dose Escalation will involve enrolling sequential cohorts with increasing doses of NDI-219216 administered daily in repeating 28-day treatment cycles. The Dose Limiting Toxicity review period for each cohort will be 21 days for each patient enrolled, with review by a Safety Review Committee prior to escalation to the next dose level.

Who Is Running the Clinical Trial?

Nimbus Wadjet, Inc.

Lead Sponsor

Trials

1

Recruited

130+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

Cediranib, when combined with standard chemotherapy (cisplatin and gemcitabine), showed promising anti-tumor activity in advanced non-small cell lung cancer, with a response rate of 26.7% among all patients and 33.3% among those evaluable.

The study found that cediranib can be safely administered at a daily dose of 30 mg without dose-limiting toxicities, although some manageable side effects like fatigue and diarrhea were noted, indicating its potential for further development in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. Goss, G., Shepherd, FA., Laurie, S., et al.[2022]

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

References

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

Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). [2015]

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

A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. [2022]

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

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. [2018]

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

Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. [2022]