Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas

NCT01088815 | Completed Phase 2 Results DMC

• 2 other identifiers: J1013NA_00036883
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Metastatic Pancreatic Cancer

Keywords

Adenocarcinoma; Hedgehog; Neoplasms; Digestive System Diseases; Neoplasms by Site; Digestive System Neoplasms; Neoplasms by Histologic Type; Pancreatic Neoplasms; Pancreatic Diseases; Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel.

  Number of months from time first therapy received to the earliest documented disease progression or death from any cause.

  6 years

• Safety of Combination Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas as Assessed by Number of Grade 3 or 4 Adverse Events

  Number of grade 3 or 4 adverse events as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.0) that occur after Cycle 2, Day 1

  6 years

Secondary Outcomes (4)

• Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Overall Survival

  6 years

• Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Tumor Response

  6 years

• Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Changes in Pancreatic Cancer Stem Cell

  6 years

• Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Hedgehog Signaling Pathway Downregulation

  6 years

Study Arms (1)

Gemcitabine, nab-paclitaxel, GDC-0449

EXPERIMENTAL

Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib)

Drug: Gemcitabine, nab-Paclitaxel, GDC-0449

Interventions

Gemcitabine, nab-Paclitaxel, GDC-0449 DRUG

1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily

Gemcitabine, nab-paclitaxel, GDC-0449

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cells tumors are excluded. Biopsy within 14 days of starting treatment.
• Patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Patient has NOT received previous radiotherapy, surgery or chemotherapy or investigational drug therapy for the treatment of metastatic disease. If the patient received radiotherapy, chemotherapy or investigational therapy in the adjuvant setting it should be completed 3 weeks prior to enrollment. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least six months after completing the last dose of gemcitabine
• Age \>18 years.
• Life expectancy of greater than 1 month.
• ECOG performance status 0 or 1 (Karnofsky \>70%).
• Patients must have adequate organ and marrow function

You may not qualify if:

• Patient had received chemotherapy or radiotherapy for metastatic disease
• Patient is receiving other investigational agents.
• Patient has known brain metastases, unless previously treated and well controlled for at least three months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study.
• Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.
• Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded
• Patient has undergone a major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ) within four weeks prior to Day 1 of treatment on this study.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Stand Up To Cancer: collaborator
• Genentech, Inc.: collaborator
• Celgene Corporation: collaborator

Study Sites (3)

Translational Genomics Research Institute (TGen)

Scottsdale, Arizona, 85258, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• De Jesus-Acosta A, Sugar EA, O'Dwyer PJ, Ramanathan RK, Von Hoff DD, Rasheed Z, Zheng L, Begum A, Anders R, Maitra A, McAllister F, Rajeshkumar NV, Yabuuchi S, de Wilde RF, Batukbhai B, Sahin I, Laheru DA. Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma. Br J Cancer. 2020 Feb;122(4):498-505. doi: 10.1038/s41416-019-0683-3. Epub 2019 Dec 20.

  PMID: 31857726 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma; Neoplasms; Digestive System Diseases; Neoplasms by Site; Digestive System Neoplasms; Neoplasms by Histologic Type; Pancreatic Diseases; Carcinoma

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; HhAntag691

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Endocrine System Diseases; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Ana De Jesus Acosta
• Organization: Johns Hopkins SKCCC

adejesu1@jhmi.edu

443-287-0411

Study Officials

• Daniel Laheru, MD

  Sidney Kimmel Comprehensive Cancer Center JHMI

  PRINCIPAL INVESTIGATOR

• Ana De Jesus-Acosta, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2010
• First Posted: March 17, 2010
• Study Start: September 17, 2010
• Primary Completion: December 1, 2017
• Study Completion: February 17, 2018
• Last Updated: April 26, 2019
• Results First Posted: April 26, 2019

Record last verified: 2019-04

Locations

US (3)