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

Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)

http://www.clinicaltrials.gov/ct2/show/NCT01096732?term=GDC-0449
Purpose
This clinical trial is looking at the effect of a new drug called GDC-0449 in patients with cancer of the pancreas. Laboratory studies have shown that this drug blocks a process in pancreatic cells thought to be involved in cancer development and spread. This process is called the 'Hedgehog signalling pathway'. As yet, it is unclear whether blocking hedgehog signalling will directly affect the tumour cells themselves or the surrounding normal tissue. Understanding this distinction will help improve treatment strategies for pancreatic cancer. Patients will be offered to participate in this research study if they have localised pancreatic cancer that can be removed by surgery. In the period between diagnosis and surgery the investigators do not normally treat patients, however in this trial the investigators will ask patients to take GDC-0449 during the approximately two weeks until the day of surgery. All patients that enter this study will have undergone a diagnostic biopsy of the pancreatic tumour and the investigators will collect a second sample of the tumour at surgery. The main question of this study is whether the investigators can detect a change in hedgehog signalling in the normal tumour surrounding tissue. Furthermore the investigators will look very carefully whether this treatment is safe for patients. All problems before and after surgery will be carefully documented and the investigators have defined strict rules to stop the study if the investigators observe serious problems.
Estimated Enrollment: 20
Study Start Date: July 2010
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas

http://clinicaltrials.gov/ct2/show/NCT01088815?term=gdc-0449
Purpose
This is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog inhibitor (GDC-0449) in combination with chemotherapy (gemcitabine and nab-Paclitaxel).
Estimated Enrollment: 80
Study Start Date: May 2010
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

GDC-0449 and RO4929097 in Treating Women With Advanced Breast Cancer PI

http://clinicaltrials.gov/ct2/show/NCT01071564 PII
PURPOSE: This phase I trial is studying the side effects and best dose of giving GDC-0449 together with RO4929097 in treating women with advanced breast cancer.
Estimated Enrollment: 36
Study Start Date: November 2009
Estimated Primary Completion Date: September 2010

Basal Cell Nevus Syndrome (BCNS) PII

http://clinicaltrials.gov/ct2/show/NCT00957229?term=GDC-0449
The purpose of this study is to reduce the number of new surgically eligible BCCs by 50% appearing during month 3-18 of medication ingestion.

Study Start Date: August 2009
Estimated Study Completion Date: March 2013

Previous Genentech-Sponsored Phase I or II Cancer Study PII

http://clinicaltrials.gov/ct2/show/NCT00959647?term=GDC-0449
This is a multicenter, open-label extension study. Patients receiving GDC-0449 in a Genentech-sponsored study who have completed the parent study or who continue to receive GDC-0449 at the time of the parent study closure are eligible for continued treatment on this protocol.

Study Start Date: August 2009
Estimated Primary Completion Date: August 2017

Metastatic Pancreatic Cancer PI

http://clinicaltrials.gov/ct2/show/NCT00878163?term=GDC-0449
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449 with or without gemcitabine hydrochloride in treating patients with metastatic pancreatic cancer or solid tumors that cannot be removed by surgery.

Study Start Date: March 2009
Estimated Primary Completion Date: November 2009

Gemcitabine Hydrochloride With or Without GDC-0449 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer PII

http://clinicaltrials.gov/ct2/show/NCT01064622?term=hedgehog
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 more effective than gemcitabine hydrochloride alone in treating patients with pancreatic cancer.
PURPOSE: This randomized phase II trial is studying gemcitabine hydrochloride and GDC-0449 to see how well they work compared with gemcitabine hydrochloride alone in treating patients with recurrent or metastatic pancreatic cancer.

Study Start Date: September 2009
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Advanced Stomach Cancer or Gastroesophageal Junction Cancer PII

http://clinicaltrials.gov/ct2/show/NCT00982592?term=GDC-0449
This randomized phase II trial is studying giving combination chemotherapy together with GDC-0449 to see how well it works compared with giving combination chemotherapy without GDC-0449 in treating patients with advanced stomach cancer or gastroesophageal junction cancer.

Study Start Date: September 2009
Estimated Primary Completion Date: April 2011

Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists P1

http://clinicaltrials.gov/ct2/show/NCT00968981?term=GDC-0449
This is a two stage, Phase Ib study designed to describe the pharmacokinetics of GDC-0449 in patients with advanced solid tumors that are refractory to treatment or for whom no standard therapy exists.
Estimated Enrollment: 60
Study Start Date: September 2009

Advanced Basal Cell Carcinoma PII

http://clinicaltrials.gov/ct2/show/NCT00833417?term=GDC-0449
This is a Phase II, single-arm, two-cohort multicenter clinical trial evaluating the efficacy and safety of GDC-0449 in patients with advanced BCC. All patients will receive GDC-0449 until evidence of progression, intolerable toxicities most probably attributable to GDC-0449, or withdrawal from the study.
Study Start Date: January 2009
Estimated Primary Completion Date: July 2012

Extensive-Stage Small Cell Lung Cancer PII

http://clinicaltrials.gov/ct2/show/NCT00887159?term=GDC-0449
Drugs used in chemotherapy, such as cisplatin and etoposide phosphate, 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. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving cisplatin and etoposide are more effective when given together with GDC-0449 or cixutumumab in treating small cell lung cancer
http://clinicaltrials.gov/ct2/show/NCT0 ... m=GDC-0449
Study Start Date: July 2009
Estimated Primary Completion Date: December 2010

Young Patients With Medulloblastoma PI

http://clinicaltrials.gov/ct2/show/NCT00822458?term=GDC-0449
This phase I trial is studying the side effects and best dose of GDC-0449 in treating young patients with medulloblastoma that is recurrent or did not respond to previous treatment.
Study Start Date: January 2009
Estimated Primary Completion Date: August 2010

Adult Patients With Recurrent or Refractory Medulloblastoma PII

http://clinicaltrials.gov/ct2/show/NCT00939484?term=GDC-0449
This phase II trial is studying how well GDC-0449 works in treating adult patients with recurrent or refractory medulloblastoma
Study Start Date: June 2009
Estimated Primary Completion Date: September 2010

Recurrent Glioblastoma Multiforme PII

http://clinicaltrials.gov/ct2/show/NCT00980343?term=GDC-0449
This randomized phase II trial is studying how well GDC-0449 works in treating patients with recurrent glioblastoma multiforme that can be removed by surgery.
Study Start Date: October 2009
Estimated Primary Completion Date: April 2010

First-Line Therapy for Metastatic Colorectal Cancer PII

http://clinicaltrials.gov/ct2/show/NCT00636610?term=GDC-0449
This is a randomized, placebo-controlled, double-blind study of GDC-0449 added to biochemotherapy standard-of-care regimens for metastatic CRC, with treatment until disease progression. Patients will receive either FOLFOX or FOLFIRI chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use will be made by the treating physician and patient. Patients will be randomized to receive GDC-0449 or placebo and will be stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease is present at baseline.
Study Start Date: March 2008
Estimated Primary Completion Date: March 2011

Maintenance Therapy in Patients With Ovarian Cancer PII

http://clinicaltrials.gov/ct2/show/NCT00739661?term=GDC-0449
The proposed study is a Phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial of GDC-0449 in patients with ovarian cancer in a second or third complete remission. Patients will be randomized in a 1:1 ratio to either GDC-0449 or placebo. Randomization will be stratified based on whether their cancer is in a second or third complete remission.
Study Start Date: September 2008
Estimated Primary Completion Date: January 201

Curis Announces Positive Results in Genentech Pivotal Phase II Clinical Trial of GDC-0449 in Advanced Basal Cell Carcinoma

LEXINGTON, Mass.--(BUSINESS WIRE)-- Curis, Inc. (NASDAQ:CRIS - News), a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced a positive outcome from a pivotal Phase II clinical trial conducted by Roche and Genentech, Curis’ collaborator and a wholly owned member of the Roche Group, of GDC-0449, a first-in-class hedgehog pathway inhibitor, in patients with advanced basal cell carcinoma (BCC). Genentech informed Curis that the study met its primary endpoint of achieving a target overall response rate, showing that GDC-0449 shrank advanced BCC tumors in a pre-defined percentage of people in the study. A preliminary safety assessment showed the most common adverse events were consistent with previous experience with vismodegib. A detailed safety assessment is ongoing. Roche has indicated that it anticipates making at least one regulatory submission in 2011 to seek approval to commercialize GDC-0449.

Genentech plans to submit the data from the clinical trial for presentation at a future medical meeting.

Roche also informed Curis that GDC-0449 (also known as RG3616) now has a generic name approved by the World Health Organization, vismodegib (pronounced vis-mo-DE-jib).

"We are extremely pleased by the highly encouraging outcome of this study, particularly since there is currently no standard of care for patients with this serious disease,” said Dan Passeri, Curis President and Chief Executive Officer. “We look forward to Genentech’s presentation of the study data in more detail in the near future, and to its planned regulatory submissions for vismodegib.”

For more information about ongoing studies of vismodegib in BCC, patients and doctors can contact the Genentech clinical trial call center at (888) 662-6728 or visit http://www.clinicaltrials.gov.

About the Pivotal Phase II Trial (ERIVANCE BCC/SHH4476g)

ERIVANCE BCC is an international, single-arm, multi-center, two-cohort, open-label Phase II study that enrolled 104 patients with advanced BCC, including metastatic and/or locally advanced BCC, defined as patients whose lesions are not appropriate for surgery, or for whom surgery would result in substantial deformity. Study participants received 150 mg vismodegib once daily until disease progression. The primary endpoint of the study was overall response rate (tumor shrinkage) as assessed by independent reviewers. Secondary endpoints of the study included overall response rate as assessed by study investigators, duration of response, progression-free survival, overall survival and the safety profile. A preliminary safety assessment showed the most common adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhea. Serious adverse events were observed, including fatal events. The deaths are being further evaluated, but do not appear to be related to vismodegib.

About Basal Cell Carcinoma

According to the American Cancer Society, BCC is the most common type of skin cancer and accounts for approximately 80 percent of all diagnosed skin cancers. The disease is generally considered curable when the cancer is restricted to a small area of the skin. However, in a small group of people, if the disease is left untreated or does not respond to treatment, the cancer may advance further into the skin, bones or other tissues. In rare cases, BCC may advance or spread to other parts of the body, at which point the disease can become difficult to treat and life-threatening.

About Vismodegib and the Hedgehog Pathway

Vismodegib is designed to selectively inhibit signaling in the Hedgehog pathway by targeting a protein called Smoothened. The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and becomes less active in adults. However, mutations in the pathway that reactivate Hedgehog signaling are seen in several different types of cancer. Abnormal signaling in the Hedgehog pathway is implicated in the majority of BCC cases.

Genentech is also evaluating vismodegib in a Phase II trial in people with operable forms of BCC, which opened in October 2010. Additionally, vismodegib is being evaluated by third-party investigators in a number of other cancers and in people with BCC who have Gorlin syndrome. Gorlin syndrome is a condition that affects many areas of the body and increases the risk of developing BCC. For more information, visit http://www.clinicaltrials.gov.