OnCo
ideasIdea

A prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compression

Nerve damage from taxanes and platinum is common, often permanent and has no approved preventive. Test the most promising candidates head to head in one programme.

Chemotherapy-induced peripheral neuropathy affects a large share of patients treated with taxanes, platinum or bortezomib and drives dose reduction. SARM1, an executioner of axon degeneration, is validated genetically in mouse models and inhibitors are in early clinical development for other neuropathies; HDAC6 inhibitors and cryotherapy or compression of hands and feet have supportive data. The proposal is a multi-arm platform trial in adjuvant breast and colorectal cancer comparing candidate preventives against placebo with a patient-reported neuropathy endpoint (EORTC CIPN20) and quantitative sensory testing.

Hypothesis
At least one intervention reduces moderate-to-severe patient-reported neuropathy at 12 months by an absolute 15 percentage points without compromising chemotherapy dose delivery or disease-free survival.
Rationale
Axon degeneration has defined molecular executioners; cooling has already shown signals; the population is large and homogeneous, making trials fast and cheap relative to oncology drugs.
What would test it
Phase 2/3 platform trial in adjuvant taxane and oxaliplatin regimens with pre-specified futility and dose-delivery safety monitoring.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks

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