Pancreatic AdenocarcinomaPhase 2NCT01064622
Gemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer
A Phase 2 study testing Gemcitabine Hydrochloride and Vismodegib in people with Pancreatic Adenocarcinoma and Recurrent Pancreatic Carcinoma, run by National Cancer Institute (NCI) at 25 sites in United States.
Trial summary
This randomized phase I/II trial studies gemcitabine hydrochloride and vismodegib to see how well they work compared with gemcitabine hydrochloride alone in treating patients with recurrent or metastatic pancreatic cancer. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage IV Pancreatic Cancer AJCC v6 and v7
- What is being tested?
- Gemcitabine Hydrochloride and Vismodegib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 25 sitesUnited States
- Study dates
- 3 Sep 2009to 31 Jan 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
- Patients must have 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 computed tomography (CT) scan
- Patients must have either:
- Newly diagnosed chemo-naïve metastatic pancreatic cancer; only patients who have not received any chemotherapy for their metastatic disease are eligible
- Recurrent disease after curative-intent surgery which has now recurred and is metastatic; patients who have recurrent disease may have received adjuvant chemotherapy or adjuvant chemoradiation, but may not have received any chemotherapy for metastatic disease; adjuvant therapy must have been completed >= 6 months prior to the diagnosis of recurrent disease, or if not adjuvant therapy received, surgery must have been performed >= 6 months prior to the diagnosis of recurrent disease
- Age >= 21 years
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- Life expectancy > 3 months
- Karnofsky performance status >= 80%
- Granulocytes >= 1,500/mcL
- Platelet count >= 100,000/mcL
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN) (=< 5 times ULN in the presence of liver metastases)
- Creatinine within normal institutional limit (< 1.5) OR creatinine clearance >= 65 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- International normalized ratio (INR) =< 1.5 (=< 3 for patients on warfarin)
- Patients who are on warfarin anticoagulation are allowed to participate as long as they fit the following 4 criteria:
- They are therapeutic on a stable warfarin dose
- Their INR target range is no greater than 3
- They are monitored with weekly INR testing
- They have no active bleeding or pathological condition that carries high risk of bleeding Other anticoagulants, including enoxaparin (Lovenox) and fondaparinux (Arixtra) are also permitted
- Women of child-bearing potential and men must use at least one form of contraception (i.e., barrier contraception) at least 4 weeks prior to study entry and then two forms of contraception (i.e barrier contraception and one other method of contraception), for the duration of study participation, and for at least 12 months post-treatment; for appropriate methods of contraception considered acceptable; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Pregnancy Testing: Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days (at initial screening/consideration for the trial - serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
- Ability to understand and the willingness to sign a written informed consent document
- Patients with recurrent disease after curative-intent surgical resection must have sufficient archival material for correlative studies (20 unstained 5 micron slides and 20 unstained 10 micron slides, or an archival tissue block
Who cannot join
- No prior chemotherapy for metastatic pancreatic cancer; patients who have received any chemotherapy and/or radiation therapy in the adjuvant setting must have completed this therapy ≥6 months prior to enrollment on the trial at the time of recurrence
- Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to hedgehog antagonist GDC-0449 or any other agents used in this study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
- GDC-0449 inhibits CYP2C8, CYP2C9, and CYP2C19 drug metabolism enzymes in vitro at concentrations that may be clinically relevant. Therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows
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- Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
- Patients with clinically active liver disease, including active viral or other hepatitis or cirrhosis are ineligible
- Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia, defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
- No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
- Uncontrolled intercurrent illness including, but not limited to,
- Ongoing or active infection,
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449; these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GDC-0449; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Tower Cancer Research Foundation
Beverly Hills, California, 90211
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Decatur Memorial Hospital
Decatur, Illinois, 62526
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Loyola University Medical Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Weill Cornell Medical Center
New York, New York, 10065
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
City of Hope South Pasadena
South Pasadena, California, 91030
Central Illinois Hematology Oncology Center
Springfield, Illinois, 62702
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
UM Saint Joseph Medical Center
Towson, Maryland, 21204
About this study
Official title: A Multi-center, Double Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine Plus GDC-0449 (NSC 747691), a Hh Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer (10052747)
This randomized phase I/II trial studies gemcitabine hydrochloride and vismodegib to see how well they work compared with gemcitabine hydrochloride alone in treating patients with recurrent or metastatic pancreatic cancer. 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. Vismodegib may slow the growth of tumor cells. It is not yet known whether giving gemcitabine hydrochloride together with vismodegib is more effective than gemcitabine hydrochloride alone in treating patients with pancreatic cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare the progression-free survival of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 (vismodegib) versus gemcitabine plus placebo.
SECONDARY OBJECTIVES:
- To compare overall survival of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 versus gemcitabine plus placebo.
II. To compare the objective response rate of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 versus gemcitabine alone.
III. To determine the toxicity experienced by pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449.
IV. To determine the activity, in an exploratory analysis, of gemcitabine plus GDC-0449 in patients who progress on gemcitabine plus placebo.
TERTIARY OBJECTIVES:
- To determine if tumor immunohistochemical expression patterns of proteins in the Hh pathway, including sonic hedgehog (Shh), indian hedgehog (Ihh), patched tumor suppressor gene (PTCH), smoothened protein (SMO), and GLI1 and 2, within pancreatic tissue obtained at the time of curative intent surgery predict response and prognosticate outcome of patients treated with or without GDC-0449 at the time of relapse.
II. To determine the prognostic ability (relapse free survival, [RFS]) of these biologic markers for resected patients in an archival cohort of patients undergoing resection.
III. To determine expression pattern of pancreatic CSC markers, including CD44, CD24, CD133, aldehyde dehydrogenase (ALDH) and epithelial specific antigen (ESA) by immunohistochemistry (IHC) on these archival tissues in relation to Hh pathway markers and correlate these with clinical outcomes.
IV. To determine whether high baseline serum Shh, as well as changes in serum Shh during treatment, predict treatment efficacy and/or prognosticate clinical outcome.
- To determine the frequency of mutation of Hh pathway genes, PTCH, SMO, SuFU, and if the presence or absence of mutations are correlated with clinical outcome.
VI. To determine the frequency of amplification of Hh pathway genes, gene copy number by quantitative polymerase chain reaction (qPCR) of GLI1 and SMO in those tumors that have high protein expression as seen by IHC. Gene amplification will be correlated with clinical outcome.
VII. To determine if there is a correlation of K-ras mutation, and MET and RON expression, amplification, or mutation status with Hh pathway abnormalities, CSC markers, and clinical outcomes.
VIII. To determine if baseline contrast perfusion imaging volume transfer constant (Ktrans) within primary and liver metastatic lesions as measured on a 256-detector computed tomography (CT) scanner predicts objective response rates, and other clinical endpoints including progression-free survival (PFS), to treatment with gemcitabine and GDC-0449/placebo. (University of Chicago ONLY) IX. To determine if treatment with Gemcitabine and GDC-0449 improves tumor perfusion, as measured by Ktrans, over the course of treatment by serial CT scans every 2 cycles, compared to tumors treated with Gemcitabine and placebo. (University of Chicago ONLY) X. To determine if improved tumor perfusion with GDC-0449 treatment (if observed) improves objective response rates and other clinical endpoints including PFS. (University of Chicago ONLY)
OUTLINE: This is a multicenter, safety lead-in study (part I) followed by a randomized study (part II).
An initial 6 patients are enrolled in the part I portion of the study. If no dose-limiting toxicities occur in these patients, subsequent patients are enrolled in the part II portion of the study.
PART I (safety lead-in study): Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and hedgehog antagonist GDC-0449 orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART II (randomized study): Patients are stratified according to disease status (recurrent after surgery vs metastatic) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride 1000 mg/m^2 IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.
ARM II: Patients receive gemcitabine hydrochloride 1000 mg/m^2 IV over 30 minutes on days 1, 8, and 15 and hedgehog antagonist GDC-0449 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue, blood, serum, and plasma samples are collected periodically for biomarker and other analyses.
After completion of study treatment, patients are followed periodically.
- Conditions
- Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage IV Pancreatic Cancer AJCC v6 and v7
- Being tested
- Gemcitabine Hydrochloride, Hydrocortisone/Placebo, Vismodegib
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar
Given IV
Hydrocortisone/PlaceboOther
Also called Hydrocortisone Used as a Placebo
Given PO
VismodegibDrug
Also called Erivedge, GDC 0449, GDC-0449, GDC0449
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (gemcitabine hydrochloride and placebo) | Active comparator | Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II. Receives: Drug: Gemcitabine Hydrochloride; Other: Hydrocortisone/Placebo |
| Arm II (gemcitabine hydrochloride and vismodegib) | Experimental | Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Gemcitabine Hydrochloride; Drug: Vismodegib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Time from randomization to disease progression or death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
Measured: Up to 3 years
Secondary outcomes (4)
Overall Survival
Time from randomization to death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
Measured: Up to 3 years
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 6 months
Incidence of Adverse Events
Details are provided in Adverse Events section below. Reported here are percentage of patients in each arm with any grade 1 or higher adverse event, regardless of attribution.
Measured: Up to 3 years
Activity (Overall Response Rate) in Crossover Patients
RECIST response rate in patients after crossover from placebo to vismodegib arm. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2010 (estimated)
- Study start3 Sep 2009
- Primary completion9 Dec 2012
- Study completion31 Jan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hedy L Kindler, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01064622
- Sponsor's protocol ID
- NCI-2011-01454
- Other IDs
- NCI-2011-01454, 10-00099, CDR0000655378, UCCRC-8418, 09-068, 8418, N01CM00038, N01CM00071
- Status last verified
- Oct 2017
- First submitted
- 5 Feb 2010
- Last updated
- 19 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. doi: 10.1200/JCO.2015.62.8719. Epub 2015 Nov 2.
PubMed 26527777
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Double Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine Plus GDC-0449 (NSC 747691), a Hh Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer (10052747)
- ClinicalTrials.gov ID
- NCT01064622
- Acronym / sponsor ID
- NCI-2011-01454
- Conditions
- Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage IV Pancreatic Cancer AJCC v6 and v7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 3 Sep 2009 (actual)
- Primary completion
- 9 Dec 2012 (actual)
- Study completion
- 31 Jan 2013 (actual)
- First posted
- 8 Feb 2010 (estimated)
- Results
- Posted 13 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I/II trial studies gemcitabine hydrochloride and vismodegib to see how well they work compared with gemcitabine hydrochloride alone in treating patients with recurrent or metastatic pancreatic cancer. 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. Vismodegib may slow the growth of tumor cells. It is not yet known whether giving gemcitabine hydrochloride together with vismodegib is more effective than gemcitabine hydrochloride alone in treating patients with pancreatic cancer.
Detailed description
PRIMARY OBJECTIVES:
- To compare the progression-free survival of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 (vismodegib) versus gemcitabine plus placebo.
SECONDARY OBJECTIVES:
- To compare overall survival of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 versus gemcitabine plus placebo.
II. To compare the objective response rate of advanced pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449 versus gemcitabine alone.
III. To determine the toxicity experienced by pancreatic cancer patients treated with the combination of gemcitabine plus GDC-0449.
IV. To determine the activity, in an exploratory analysis, of gemcitabine plus GDC-0449 in patients who progress on gemcitabine plus placebo.
TERTIARY OBJECTIVES:
- To determine if tumor immunohistochemical expression patterns of proteins in the Hh pathway, including sonic hedgehog (Shh), indian hedgehog (Ihh), patched tumor suppressor gene (PTCH), smoothened protein (SMO), and GLI1 and 2, within pancreatic tissue obtained at the time of curative intent surgery predict response and prognosticate outcome of patients treated with or without GDC-0449 at the time of relapse.
II. To determine the prognostic ability (relapse free survival, [RFS]) of these biologic markers for resected patients in an archival cohort of patients undergoing resection.
III. To determine expression pattern of pancreatic CSC markers, including CD44, CD24, CD133, aldehyde dehydrogenase (ALDH) and epithelial specific antigen (ESA) by immunohistochemistry (IHC) on these archival tissues in relation to Hh pathway markers and correlate these with clinical outcomes.
IV. To determine whether high baseline serum Shh, as well as changes in serum Shh during treatment, predict treatment efficacy and/or prognosticate clinical outcome.
- To determine the frequency of mutation of Hh pathway genes, PTCH, SMO, SuFU, and if the presence or absence of mutations are correlated with clinical outcome.
VI. To determine the frequency of amplification of Hh pathway genes, gene copy number by quantitative polymerase chain reaction (qPCR) of GLI1 and SMO in those tumors that have high protein expression as seen by IHC. Gene amplification will be correlated with clinical outcome.
VII. To determine if there is a correlation of K-ras mutation, and MET and RON expression, amplification, or mutation status with Hh pathway abnormalities, CSC markers, and clinical outcomes.
VIII. To determine if baseline contrast perfusion imaging volume transfer constant (Ktrans) within primary and liver metastatic lesions as measured on a 256-detector computed tomography (CT) scanner predicts objective response rates, and other clinical endpoints including progression-free survival (PFS), to treatment with gemcitabine and GDC-0449/placebo. (University of Chicago ONLY) IX. To determine if treatment with Gemcitabine and GDC-0449 improves tumor perfusion, as measured by Ktrans, over the course of treatment by serial CT scans every 2 cycles, compared to tumors treated with Gemcitabine and placebo. (University of Chicago ONLY) X. To determine if improved tumor perfusion with GDC-0449 treatment (if observed) improves objective response rates and other clinical endpoints including PFS. (University of Chicago ONLY)
OUTLINE: This is a multicenter, safety lead-in study (part I) followed by a randomized study (part II).
An initial 6 patients are enrolled in the part I portion of the study. If no dose-limiting toxicities occur in these patients, subsequent patients are enrolled in the part II portion of the study.
PART I (safety lead-in study): Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and hedgehog antagonist GDC-0449 orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART II (randomized study): Patients are stratified according to disease status (recurrent after surgery vs metastatic) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride 1000 mg/m^2 IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.
ARM II: Patients receive gemcitabine hydrochloride 1000 mg/m^2 IV over 30 minutes on days 1, 8, and 15 and hedgehog antagonist GDC-0449 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue, blood, serum, and plasma samples are collected periodically for biomarker and other analyses.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (gemcitabine hydrochloride and placebo) | Active comparator | Drug: Gemcitabine Hydrochloride, Other: Hydrocortisone/PlaceboPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II. |
| Arm II (gemcitabine hydrochloride and vismodegib) | Experimental | Drug: Gemcitabine Hydrochloride, Drug: VismodegibPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
- Patients must have 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 computed tomography (CT) scan
- Patients must have either:
- Age >= 21 years
- Life expectancy > 3 months
Key exclusion criteria (18 listed)
- No prior chemotherapy for metastatic pancreatic cancer; patients who have received any chemotherapy and/or radiation therapy in the adjuvant setting must have completed this therapy ≥6 months prior to enrollment on the trial at the time of recurrence
- Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to hedgehog antagonist GDC-0449 or any other agents used in this study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gemcitabine HydrochlorideAlso: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, GemzarGiven IV | Drug | Arm I (gemcitabine hydrochloride and placebo), Arm II (gemcitabine hydrochloride and vismodegib) |
| Hydrocortisone/PlaceboAlso: Hydrocortisone Used as a PlaceboGiven PO | Other | Arm I (gemcitabine hydrochloride and placebo) |
| VismodegibAlso: Erivedge, GDC 0449, GDC-0449, GDC0449Given PO | Drug | Arm II (gemcitabine hydrochloride and vismodegib) |
Primary outcome
Progression-free Survival
Time frame: Up to 3 years
Time from randomization to disease progression or death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
4 secondary outcomes
Overall Survival
Time frame: Up to 3 years
Objective Response Rate
Time frame: Up to 6 months
Incidence of Adverse Events
Time frame: Up to 3 years
Activity (Overall Response Rate) in Crossover Patients
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26527777Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. doi: 10.1200/JCO.2015.62.8719. Epub 2015 Nov 2.
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RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hedy L Kindler principal investigator
University of Chicago Comprehensive Cancer Center
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine Hydrochloride and Vismodegib in people with Pancreatic Adenocarcinoma and Recurrent Pancreatic Carcinoma, run by National Cancer Institute (NCI) at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01064622, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.