Trial Summary

This interesting trial is a multi-cancer effort including NET.  The phase I clinical trial of Procaspase Activating Compound-1 (PAC-1), a drug that spurs programmed cell death in cancer cells, found only minor side effects in patients with end-stage cancers. The drug stalled the growth of tumors in the five people in the trial with neuroendocrine cancers and reduced tumor size in two of those patients. It also showed some therapeutic activity against sarcomas, scientists and clinicians report in the British Journal of Cancer.  As of March 1, 2019, only patients with neuroendocrine tumors will be enrolled in Component 1 of this study. PAC-1 is taken orally on days 1-21 of a 28-day cycle. The maximum tolerated dose (MTD) of PAC-1 (5 dose levels) will be determined using a modified-Fibonacci dose-escalation 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.

Results

Forty-eight patients were enrolled with 33 completing ≥2 cycles of therapy and evaluable for DLT. DL 7 (750 mg/day) was established as the recommended phase 2 dose, with grade 1 and 2 neurological adverse events noted, while NNCF testing showed stable neurologic and cognitive evaluations. PAC-1’s t_1/2 was 28.5 h after multi-dosing, and systemic drug exposures achieved predicted therapeutic concentrations. PAC-1 clinical activity was observed in patients with neuroendocrine tumour (NET) with 2/5 patients achieving durable partial response.

Conclusions

PAC-1 dose at 750 mg/day was recommended for phase 2 studies. The activity of PAC-1 in treatment-refractory NET warrants further investigation.

Note a Phase 2 trial is not yet listed so this post is informational only.  The phase 1 trial took place in 3 US locations, Illinois, Maryland and Minnesota.