Curis Hedgehog and Beyond --plus multi-targeting cancer inhibitors

All of the following compounds work at blocking the activating forms of a Hh signaling protein called "SMO." IP-926 team took a well known inhibitor and made it work better. GDC-0449 said I know I want to inhibit SMO lets make a brand new inhibitor (or class of molecules). Itraconazole was found during a Stanford screen and has been in use for the last 25 years for fungal infections.

--IP-926 synthetic derivative of Cyclopamine ...

Itraconazole, is an already approved drug as an oral antifungal but it has been show by a research team to also inhibit the Hh pathway. It was also shown to inhibit the pathway differently than the current SMO inhibitors in the clinic.

http://clinicaltrials.gov/ct2/show/NCT01108094

BCCs are the most common human cancer in the US and affect over 1 million people. There is no effective drug to prevent basal cell carcinomas ...

NEW ORLEANS - An oral inhibitor of the hedgehog pathway proved dramatically effective for the treatment and prevention of basal cell carcinomas in patients with basal cell nevus syndrome in a phase II study.

Indeed, the randomized double-blind trial was halted early for ethical reasons because patients assigned to vismodegib, formerly known as GDC-0449, demonstrated a 25-fold reduction in the rate of new basal cell carcinomas (BCCs), compared with placebo-treated controls, Dr. Jean Y. Tang ...

A Study of TAK-441 in Adult Patients With Advanced Nonhematologic Malignancies P1
http://clinicaltrials.gov/ct2/show/NCT01204073
This is the first study in which TAK-441 is administered to humans. The patient population will consist of adults aged 18 or older who have advanced nonhematologic malignancies and for whom standard treatment is no longer effective or does not offer curative or life-prolonging potential. Following completion of the dose escalation study, patients will be enrolled as part of 2 expansion cohorts. ...

The emergence of new small molecules with capacity of blocking the Hedgehog signaling pathway provides a novel therapeutic approach in pancreatic adenocarcinoma treating the primary tumor, stroma, systemic metastases and pancreatic cancer stem cells by hedgehog pathway inhibition. This phase 2 clinical trial will evaluate the progression free survival (PFS) in patients with previously untreated metastatic pancreatic adenocarcinoma. We hypothesize that the combination of cytotoxic agents (gemcitabine and nab-paclitaxel) with the Hedgehog inhibitor GDC-0449 may ...

http://clinicaltrials.gov/ct2/show/NCT01071564

The Notch like the Hedgehog pathway is very important in stem cell maintenance and repair of cells. This is also a Roche Compound.

http://www.cnb.uam.es/~jlpompa/


The second is a blocker of Hh (hedgehog) signaling, GDC-0449, which we are combining with a blocker of gamma secretase (RO4929097) in a novel study for people with recurrent sarcomas. We are seeking funding to perform this multi-center study, focusing on biopsies ...

http://clinicaltrials.gov/ct2/show/NCT01064622
Gemcitabine Hydrochloride With or Without GDC-0449 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer
Purpose
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. GDC-0449 may slow the growth of tumor cells. It is not yet known whether giving gemcitabine hydrochloride together with GDC-0449 is ...

Advanced Solid Tumors
http://clinicaltrials.gov/ct2/show/NCT00880308?term=LDE225 PI
This first-in-human dose-escalation study is to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of LDE225 given orally on a daily dosing schedule in patients with advanced solid tumors.

• Study Start Date: March 2009
• Estimated Primary Completion Date: December 2010

Skin Basal Cell Carcinomas in Gorlin's Syndrome Patients PI / PII
http://clinicaltrials.gov/ct2/show/NCT00961896?term=LDE225
A double-blind, randomized, vehicle-controlled Proof of Concept (PoC) study to evaluate the safety, local tolerability, pharmacokinetics and pharmacodynamics of ...

Advanced and/or Metastatic Solid Tumor Malignancies PI
http://clinicaltrials.gov/ct2/show/NCT00761696?term=IPI-926
A Phase 1 Study of IPI-926 in Patients With Advanced and/or Metastatic Solid Tumor Malignancies

A Study Evaluating IPI-926 in Combination With Gemcitabine in Patients With Metastatic Pancreatic Cancer PI/PII
http://clinicaltrials.gov/ct2/show/NCT01130142
Study IPI-926-03 is a Phase 1b/2 clinical trial to evaluate IPI 926 in combination with gemcitabine in patients with previously untreated metastatic pancreatic cancer. Phase 1b is designed as a dose escalation study. Once the maximum ...

First Line Colon Cancer

Completed Enrollment Q2 2009 N=199

Advanced Ovarian Cancer

Completed Enrollment Q4 2009 N=104

Advanced BCC

FPI Q1 2009 N=100