Manganese & Pancreatic Cancer: Promising New Treatment?

observational-study PMID: 38039992

Quick Summary: Researchers are exploring a new drug, avasopasem manganese, to boost the effectiveness of radiation therapy for pancreatic cancer. Early results suggest it may improve outcomes and reduce side effects.

What The Research Found

This study looked at combining radiation therapy with a drug called avasopasem manganese in patients with pancreatic cancer. The results showed that patients taking avasopasem manganese along with radiation therapy had better outcomes compared to those who received radiation alone. The researchers found that the combination might be more effective and safer.

Study Details

Who was studied: 42 people with pancreatic cancer that had not spread too far. They had already received chemotherapy.

How long: The study lasted for a period of time, with data collected up to June 2021.

What they took: Participants received radiation therapy and either avasopasem manganese (a drug) or a placebo (a "dummy" pill).

What This Means For You

This research is still in the early stages. However, it suggests that avasopasem manganese could be a helpful addition to radiation therapy for some pancreatic cancer patients. This could lead to better outcomes and fewer side effects. Important Note: This study used a specific drug (avasopasem manganese) and is not about taking manganese supplements.

Study Limitations

The study was small, so more research is needed.

The study focused on short-term results, so we don't know the long-term effects yet.

Most participants were white, so the results may not apply to everyone.

The study was funded by the company that makes the drug, which could influence the results.

Key Findings

This phase 1b/2 trial evaluated avasopasem manganese, a selective dismutase mimetic, combined with stereotactic body radiotherapy (SBRT) in patients with localized pancreatic ductal adenocarcinoma. The primary goal was to determine the optimal SBRT dose with or without avasopasem. Results showed that the avasopasem group met predefined efficacy and safety boundaries, with 89% (16/18) at 50 Gy and 100% (6/6) at 55 Gy achieving late-onset EffTox efficacy responses. In contrast, the placebo group had lower efficacy (50% at 50 Gy, 75% at 55 Gy) and was terminated early. Bayesian modeling recommended 50–55 Gy SBRT with avasopasem for further study.

Study Design

The study was an adaptive, randomized, double-blind, placebo-controlled trial conducted at six U.S. academic centers. It enrolled 42 patients (median age 71 years [IQR 63–75]; 55% male, 88% White) with borderline resectable or locally advanced pancreatic cancer who had undergone ≥3 months of chemotherapy. Participants received SBRT (50–60 Gy in five fractions) with either avasopasem (90 mg/day IV) or placebo, with real-time dose adjustments via Bayesian safety/efficacy estimates.

Dosage & Administration

Avasopasem (90 mg) or placebo was administered intravenously daily immediately before SBRT. SBRT doses were adaptively assigned (50, 55, or 60 Gy in five fractions) based on trial outcomes. Treatment allocation was blinded to patients and physicians, but SBRT dose was not masked.

Results & Efficacy

Efficacy:
Avasopasem group: 89% (50 Gy) and 100% (55 Gy) achieved EffTox responses.
Placebo group: 50% (50 Gy) and 75% (55 Gy) achieved EffTox responses.
Bayesian modeling identified 50–55 Gy with avasopasem as optimal for further study.
Safety:
Serious adverse events: 17% (placebo) vs. 25% (avasopasem).
Grade 3–4 events in avasopasem group included acute kidney injury, colitis, and pneumonia (1–4% incidence).
No treatment-related deaths; one late avasopasem-group death (sepsis post-duodenal obstruction) was possibly SBRT-related.

Limitations

Small sample size (n=42) with early termination of the placebo arm, limiting comparative power.
Short follow-up (data cutoff June 2021); long-term efficacy and safety outcomes unknown.
Demographics skewed toward White participants (88%), reducing generalizability.
Primary endpoint focused on acute toxicity and short-term efficacy, not overall survival or progression-free survival.
Adaptive design may introduce bias in dose selection.

Clinical Relevance

This trial suggests avasopasem manganese may enhance SBRT efficacy in localized pancreatic cancer, supporting its investigation in larger phase 2 trials (e.g., GRECO-2). However, avasopasem is a synthetic dismutase mimetic, not a dietary manganese supplement, and its use is restricted to this oncological context. Results highlight the importance of optimizing radiation doses with radioprotective agents but do not support general manganese supplementation for cancer patients. Further research is needed to confirm these findings in diverse populations and assess long-term benefits.

Note: This study was funded by Galera Therapeutics, the manufacturer of avasopasem. Conflict-of-interest disclosures should be considered in interpretation.