UCSF’s Clinical Trials

Posted 22 March 2016

Yesterday Irene and I went to UCSF to meet with the clinical trials folks. Overall, we were impressed with the doctor, who explained things to us clearly.

He agreed that radiation was a sensible next step, as it should provide some immediate relief, and it will take time to get into a clinical trial. UCSF has two trials for which I’m a potential match, but neither of them have openings at the moment. New openings come up from time to time, but I have no sense of their frequency.

These are the titles of the two trials:

1. A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10 in Advanced Solid Tumors and in Combination with FOLFIRI for Patients with Previously Treated Metastatic Colorectal Cancer
2. A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered CB-5083 in Patients with Advanced Solid Tumors

RSPO-LGR Pathway

The first trial is aimed at colon cancer, but since there is nothing aimed at duodenal cancer because of its rarity, colon and pancreatic cancer treatments are my best bets. It is a chemo regimen, similar to the one I was on before, with the addition of another drug, OMP-131R10. It targets something called the RSPO-LGR pathway. Here’s the description, on the off chance that you can make any sense out of it:

The RSPO-LGR pathway is believed to be an important cancer stem cell pathway. Human R-spondin (RSPO) proteins signal through the leucine-rich repeat-containing G-coupled receptors (LGRs). Antibodies that disrupt binding of RSPO proteins to LGRs, or that disrupt RSPO activation of LGR signaling, are potential anti-cancer agents. OncoMed has identified multiple antibodies targeting the RSPO-LGR pathway. OncoMed initiated a Phase 1a/1b clinical study for its first antibody targeting the RSPO-LGR pathway, anti-RSPO3 (OMP-131R10). A proprietary biomarker to prospectively screen patients for expression of RSPO is being developed in conjunction with this clinical program. Anti-RSPO3 has demonstrated activity in preclinical models against a variety of major tumor types, including colon, lung and ovarian cancers.

P97 Inhibitor

The second trial is for a drug that is an inhibitor of p97, a cancer-causing gene. Here’s the technical summary:

CB-5083 is a potent, highly selective, oral p97 inhibitor with broad in vivo activity in both multiple myeloma and solid tumor xenografts. CB-5083 is a potent inhibitor of endoplasmic reticulum associated degradation and induces a lethal unfodled protein response. Multiple myeloma is a cancer with a well-known dependence on protein homeostasis for survival with the proteasome inhibitors bortezomib and carfilzomib as FDA approved drugs. These agents are not effective in solid tumors owing to both chemistry and pharmacology limitations. Not only has Cleave demonstrated activity in solid tumors with CB-5083, we have also identified molecular features that correlate to increased anti-tumor activity in preclinical models.

At this point, I’m in the queue to be screened for these trials, but the soonest I could participate would be in about 6 weeks (2 weeks of radiation and then 4 weeks post-radiation to meet the trial’s requirements). It may well be much longer (if ever) before there is an opening. If there is an opening, I will need to decide if the likelihood of benefit justifies the hassle and side effects.

This leaves clinical trials at other facilities as the remaining frontier to explore. I plan to begin exploring this while undergoing the radiation treatments.

Emotionally Challenging

While there wasn’t really any news in the last couple of doctor’s visits, the doctors’ comments have driven home the seriousness of my situation. The sobering view, combined with increasing pain in my gut, has made it tough to keep a positive outlook.

I am soldiering on, though, and I’m still finding enjoyable times every day. I am back on pain killers most days, which is discouraging. I have high hopes for the radiation to give me a respite from the pain and a consequent improvement in my outlook for a few months.