Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma
Study Details
Study Description
Brief Summary
This is an open-label phase 1/2 study that will combine the chemotherapy agents gemcitabine and nab-paclitaxel with an oral hedgehog inhibitor LDE225 (Sonidegib). The objective is to assess tolerability and the resection rate of patients with borderline resectable pancreatic adenocarcinoma who use this treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
The investigators propose treating 6-12 patients during the phase 1 portion and 40 patients in the phase 2 stage.
Phase 1 Stage:
Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with escalating doses (400mg, or 600mg, or 800mg) of LDE-225. After completion of neoadjuvant therapy, the subjects will receive combined chemotherapy and radiation. Then subjects who are eligible for resection will go ahead with surgery. Following resection, subjects will complete two additional cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 in combination with LDE-225.
Phase 2 Stage: In the Phase 2 stage the patients will be randomized to receive gemcitabine and nab-paclitaxel with or without the hedgehog inhibitor LDE225:
-
Arm A: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose.
-
Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15.
After completion of neoadjuvant therapy, the subjects will receive combined chemotherapy and radiation. Then subjects who are eligible for resection will go ahead with surgery. Following resection, subjects will complete two additional cycles of the pre-surgical therapy.
Several correlative laboratory studies will be conducted during the course of this study. They were designed around the goals of providing us with a better understanding of how the stroma-tumor interaction and the intra-tumoral drug levels of gemcitabine are affected with the use of LDE-225. Two additional biopsies are required to participate in this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I-Gem,nab-paclitaxel,LDE225-600mg Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily. |
Drug: LDE225-600mg
Phase I: oral LDE225 (Sonidegib), 600mg daily.
Phase II Arm A: LDE225 at the recommended phase 2 dose on Days 1, 8 and 15. Cycles repeated every 28 days.
Other Names:
Drug: Gemcitabine
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: nab-paclitaxel
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
|
| Active Comparator: Phase II-Arm A:Gem,nab-paclitaxel,LDE225 Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose. Cycles repeated every 28 days. |
Drug: LDE225-600mg
Phase I: oral LDE225 (Sonidegib), 600mg daily.
Phase II Arm A: LDE225 at the recommended phase 2 dose on Days 1, 8 and 15. Cycles repeated every 28 days.
Other Names:
Drug: Gemcitabine
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: nab-paclitaxel
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: LDE225-400mg
Phase I: oral LDE225 (Sonidegib), 400mg daily.
Other Names:
Drug: LDE225-800mg
Phase I: oral LDE225 (Sonidegib), 800mg daily.
Other Names:
|
| Active Comparator: Phase II-Arm B:Gem,nab-paclitaxel Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days. |
Drug: Gemcitabine
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: nab-paclitaxel
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
|
| Experimental: Phase I-Gem,nab-paclitaxel,LDE225-400mg Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily. |
Drug: Gemcitabine
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: nab-paclitaxel
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: LDE225-400mg
Phase I: oral LDE225 (Sonidegib), 400mg daily.
Other Names:
|
| Experimental: Phase I-Gem,nab-paclitaxel,LDE225-800mg Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily. |
Drug: Gemcitabine
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: nab-paclitaxel
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Drug: LDE225-800mg
Phase I: oral LDE225 (Sonidegib), 800mg daily.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase I - Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy as Measured by Number of Participants Who Tolerated the Maximal Dose of LDE-225 [5 years]
Number of participants who tolerated the maximal dose of LDE-225 in combination with gemcitabine, nab-paclitaxel as neoadjuvant therapy in patients with borderline resectable pancreatic adenocarcinoma (PDA).
- Phase II - Resection Rate of Two Preoperative Chemotherapy Regimens in Patients With Borderline Resectable PDA [5 years]
Number of participants with borderline resectable pancreatic adenocarcinoma (PDA) who undergo resection after therapy
Secondary Outcome Measures
- Overall Survival [5 years]
Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first.
- Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response [5 years]
Number of participants who experienced complete response (CR) or partial response (PR), as defined by RECIST v1.0; where CR is a disappearance of all target lesions and PR is ≥30% reduction of target lesions.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed adenocarcinoma of the pancreas.
-
Must have borderline resectable pancreatic adenocarcinoma
-
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
-
No previous radiotherapy, surgery, chemotherapy or investigational drug therapy.
-
Age >18 years
-
Life expectancy of greater than 1 month.
-
ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
-
Adequate organ and marrow function
-
Asymptomatic for jaundice and ascites. Pain symptoms should be stable.
-
Negative serum pregnancy test
-
Sexually active males should agree to use a barrier form of contraception, even if they have had a vasectomy, during the study and for 6 months after stopping LDE225. Males should not donate sperm during treatment, and for up to six months after last dose. Sexually active females of child bearing potential agree to using highly effective contraception during study and for 20 months after final dose of LDE225.
-
Agree not to donate blood products for 12 months after stopping LDE225.
-
Willing to have two biopsies while on treatment for correlative studies.
Exclusion Criteria:
-
Patients who have had previous radiotherapy, surgical resection, chemotherapy or investigational drug therapy for pancreatic adenocarcinoma.
-
Patient has known metastatic disease.
-
History of allergic reactions attributed to compounds of similar chemical or biologic composition to LDE225 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®)
-
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 within four weeks prior to starting treatment on this study.
-
Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225.
-
Patients with neuromuscular disorders.
-
Patients with impaired cardiac function.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | United States | 21205 |
Sponsors and Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Novartis Pharmaceuticals
- The Skip Viragh Foundation
Investigators
- Principal Investigator: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center JHMI
Study Documents (Full-Text)
More Information
Publications
None provided.- J1130
- NA_00047491
Study Results
Participant Flow
| Recruitment Details | 10 subjects were screen failures. All of 13 subjects were enrolled into the Arm/group: Phase I: gem, nab-paclitaxel, and LDE225-600mg. Other Arm/group did not enroll any subjects due to early termination of the study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase I: Gem, Nab-paclitaxel, and LDE225-600mg | Phase I: Gem, Nab-paclitaxel, and LDE225-400mg | Phase I: Gem, Nab-paclitaxel, and LDE225-800mg | Phase II: Arm A - Gem, Nab-paclitaxel, and LDE 225 | Phase II: Arm B - Gemcitabine and Nab-paclitaxel |
|---|---|---|---|---|---|
| Arm/Group Description | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily. | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily. | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily. | Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose. Cycles repeated every 28 days. | Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days. |
| Period Title: Overall Study | |||||
| STARTED | 13 | 0 | 0 | 0 | 0 |
| COMPLETED | 13 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase I, Gem, Nab-paclitaxel, and LDE225-600mg | Phase I, Gem, Nab-paclitaxel, and LDE225-400mg | Phase I, Gem, Nab-paclitaxel, and LDE225-800mg | Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225 | Phase II, Arm B: Gemcitabine and Nab-paclitaxel | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I: Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 600 mg daily | Phase I: Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 400 mg daily | Phase I: Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 800 mg daily | Phase II: Arm A: Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose from Phase I. Cycles repeated every 28 days. | Phase II: Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days. | Total of all reporting groups |
| Overall Participants | 13 | 0 | 0 | 0 | 0 | 13 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
61.62
(9.32)
|
61.62
(9.32)
|
||||
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
7
53.8%
|
7
Infinity
|
||||
| Male |
6
46.2%
|
6
Infinity
|
||||
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| White or Caucasian |
11
84.6%
|
11
Infinity
|
||||
| Black or African American |
2
15.4%
|
2
Infinity
|
||||
| Others |
0
0%
|
0
NaN
|
||||
Outcome Measures
| Title | Phase I - Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy as Measured by Number of Participants Who Tolerated the Maximal Dose of LDE-225 |
|---|---|
| Description | Number of participants who tolerated the maximal dose of LDE-225 in combination with gemcitabine, nab-paclitaxel as neoadjuvant therapy in patients with borderline resectable pancreatic adenocarcinoma (PDA). |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| This measure only applies to the Phase I arms. All 13 subjects participated in the Arm/group: Phase I: gem, nab-paclitaxel, and LDE225-600mg. There were no participants enrolled in other two Arm/group as the study was terminated. |
| Arm/Group Title | Phase I: Gem, Nab-paclitaxel, and LDE225-600mg | Phase I: Gem, Nab-paclitaxel, and LDE225-400mg | Phase I: Gem, Nab-paclitaxel, and LDE225-800mg |
|---|---|---|---|
| Arm/Group Description | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily. |
| Measure Participants | 13 | 0 | 0 |
| Count of Participants [Participants] |
13
100%
|
0
NaN
|
0
NaN
|
| Title | Phase II - Resection Rate of Two Preoperative Chemotherapy Regimens in Patients With Borderline Resectable PDA |
|---|---|
| Description | Number of participants with borderline resectable pancreatic adenocarcinoma (PDA) who undergo resection after therapy |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected to assess this outcome measure as the study was terminated before Phase II. |
| Arm/Group Title | Phase II-Arm A:Gem,Nab-paclitaxel,LDE225 | Phase II-Arm B:Gem,Nab-paclitaxel |
|---|---|---|
| Arm/Group Description | Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose. Cycles repeated every 28 days. LDE225-600mg: Phase I: oral LDE225 (Sonidegib), 600mg daily. Phase II Arm A: LDE225 at the recommended phase 2 dose on Days 1, 8 and 15. Cycles repeated every 28 days. Gemcitabine: Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days. nab-paclitaxel: Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days. LDE225-400mg: Phase I: oral LDE225 (Sonidegib), 400mg daily. LDE225-800mg: Phase I: oral LDE225 (Sonidegib), 800mg daily. | Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days. Gemcitabine: Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days. nab-paclitaxel: Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days. |
| Measure Participants | 0 | 0 |
| Title | Overall Survival |
|---|---|
| Description | Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| This measure only applies to the Phase I arms. All 13 subjects participated in the Arm/group: Phase I: gem, nab-paclitaxel, and LDE225-600mg. There were no participants enrolled in other two Arm/group as the study was terminated. |
| Arm/Group Title | Phase I: Gem, Nab-paclitaxel, and LDE225-600mg | Phase I: Gem, Nab-paclitaxel, and LDE225-400mg | Phase I: Gem, Nab-paclitaxel, and LDE225-800mg |
|---|---|---|---|
| Arm/Group Description | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily. |
| Measure Participants | 13 | 0 | 0 |
| Median (Full Range) [months] |
34.3
|
| Title | Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response |
|---|---|
| Description | Number of participants who experienced complete response (CR) or partial response (PR), as defined by RECIST v1.0; where CR is a disappearance of all target lesions and PR is ≥30% reduction of target lesions. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| This measure only applies to the Phase I arms. All 13 subjects participated in the Arm/group: Phase I: gem, nab-paclitaxel, and LDE225-600mg. There were no participants enrolled in other two Arm/group as the study was terminated. |
| Arm/Group Title | Phase I: Gem, Nab-paclitaxel, and LDE225-600mg | Phase I: Gem, Nab-paclitaxel, and LDE225-400mg | Phase I: Gem, Nab-paclitaxel, and LDE225-800mg |
|---|---|---|---|
| Arm/Group Description | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily. | Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily. |
| Measure Participants | 13 | 0 | 0 |
| Count of Participants [Participants] |
3
23.1%
|
Adverse Events
| Time Frame | up to 3 years | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Only for eligible participants. There were no participants enrolled in Phase I: gem, nab-paclitaxel, and LDE225-400mg, Phase I: gem, nab-paclitaxel, and LDE225-800mg, Phase II Arm A, and Phase II Arm B because the study was terminated early | |||||||||
| Arm/Group Title | Phase I, Gem, Nab-paclitaxel, and LDE225-600mg | Phase I, Gem, Nab-paclitaxel, and LDE225-400mg | Phase I, Gem, Nab-paclitaxel, and LDE225-800mg | Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225 | Phase II, Arm B: Gemcitabine and Nab-paclitaxel | |||||
| Arm/Group Description | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle with oral LDE225, 600mg. | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle with oral LDE225, 400mg. | Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2o n days 1, 8, and 15 every 28 days cycle with oral LDE225, 800mg. | Phase II: Arm A: Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase I dose. Cycles repeated every 28 days. | Phase II: Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days. | |||||
All Cause Mortality |
||||||||||
| Phase I, Gem, Nab-paclitaxel, and LDE225-600mg | Phase I, Gem, Nab-paclitaxel, and LDE225-400mg | Phase I, Gem, Nab-paclitaxel, and LDE225-800mg | Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225 | Phase II, Arm B: Gemcitabine and Nab-paclitaxel | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/13 (15.4%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||
Serious Adverse Events |
||||||||||
| Phase I, Gem, Nab-paclitaxel, and LDE225-600mg | Phase I, Gem, Nab-paclitaxel, and LDE225-400mg | Phase I, Gem, Nab-paclitaxel, and LDE225-800mg | Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225 | Phase II, Arm B: Gemcitabine and Nab-paclitaxel | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/13 (61.5%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||
| Blood and lymphatic system disorders | ||||||||||
| elevated creatine kinase | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| Cardiac disorders | ||||||||||
| fever and tachydysrhythmia | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| Gastrointestinal disorders | ||||||||||
| abdomina pain | 3/13 (23.1%) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 |
| obstruction | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| toxic mega-colon | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| pancreatitis | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| General disorders | ||||||||||
| nausea, vomitting | 3/13 (23.1%) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 | 3/0 (Infinity) | 3 |
| Infections and infestations | ||||||||||
| spesis | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| rhabdomyolysis | 1/13 (7.7%) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 | 1/0 (Infinity) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase I, Gem, Nab-paclitaxel, and LDE225-600mg | Phase I, Gem, Nab-paclitaxel, and LDE225-400mg | Phase I, Gem, Nab-paclitaxel, and LDE225-800mg | Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225 | Phase II, Arm B: Gemcitabine and Nab-paclitaxel | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/13 (100%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||
| Blood and lymphatic system disorders | ||||||||||
| WBC decreased | 13/13 (100%) | 68 | 13/0 (Infinity) | 68 | 13/0 (Infinity) | 68 | 13/0 (Infinity) | 68 | 13/0 (Infinity) | 68 |
| Hemoglobin decreased | 12/13 (92.3%) | 60 | 12/0 (Infinity) | 60 | 12/0 (Infinity) | 60 | 12/0 (Infinity) | 60 | 12/0 (Infinity) | 60 |
| Albumin decreased | 8/13 (61.5%) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 |
| Lymphocytes decreased | 10/13 (76.9%) | 51 | 10/0 (Infinity) | 51 | 10/0 (Infinity) | 51 | 10/0 (Infinity) | 51 | 10/0 (Infinity) | 51 |
| Neutrophiles decreased | 10/13 (76.9%) | 32 | 10/0 (Infinity) | 32 | 10/0 (Infinity) | 32 | 10/0 (Infinity) | 32 | 10/0 (Infinity) | 32 |
| Platelets decreased | 8/13 (61.5%) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 | 8/0 (Infinity) | 23 |
| Gastrointestinal disorders | ||||||||||
| Constipation | 8/13 (61.5%) | 15 | 8/0 (Infinity) | 15 | 8/0 (Infinity) | 15 | 8/0 (Infinity) | 15 | 8/0 (Infinity) | 15 |
| Abdomin pain | 7/13 (53.8%) | 21 | 7/0 (Infinity) | 21 | 7/0 (Infinity) | 21 | 7/0 (Infinity) | 21 | 7/0 (Infinity) | 21 |
| General disorders | ||||||||||
| Weight loss | 10/13 (76.9%) | 19 | 10/0 (Infinity) | 19 | 10/0 (Infinity) | 19 | 10/0 (Infinity) | 19 | 10/0 (Infinity) | 19 |
| Nausea | 10/13 (76.9%) | 23 | 10/0 (Infinity) | 23 | 10/0 (Infinity) | 23 | 10/0 (Infinity) | 23 | 10/0 (Infinity) | 23 |
| Fatigue | 9/13 (69.2%) | 24 | 9/0 (Infinity) | 24 | 9/0 (Infinity) | 24 | 9/0 (Infinity) | 24 | 9/0 (Infinity) | 24 |
| Fever | 7/13 (53.8%) | 10 | 7/0 (Infinity) | 10 | 7/0 (Infinity) | 10 | 7/0 (Infinity) | 10 | 7/0 (Infinity) | 10 |
| Hepatobiliary disorders | ||||||||||
| ALT increased | 12/13 (92.3%) | 30 | 12/0 (Infinity) | 30 | 12/0 (Infinity) | 30 | 12/0 (Infinity) | 30 | 12/0 (Infinity) | 30 |
| AST increased | 10/13 (76.9%) | 34 | 10/0 (Infinity) | 34 | 10/0 (Infinity) | 34 | 10/0 (Infinity) | 34 | 10/0 (Infinity) | 34 |
| Metabolism and nutrition disorders | ||||||||||
| sodium decreased | 9/13 (69.2%) | 9 | 9/0 (Infinity) | 9 | 9/0 (Infinity) | 9 | 9/0 (Infinity) | 9 | 9/0 (Infinity) | 9 |
| Glucose increased | 12/13 (92.3%) | 52 | 12/0 (Infinity) | 52 | 12/0 (Infinity) | 52 | 12/0 (Infinity) | 52 | 12/0 (Infinity) | 52 |
| Alkaline phosphatase increased | 10/13 (76.9%) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 |
| Calcium decreased | 10/13 (76.9%) | 20 | 10/0 (Infinity) | 20 | 10/0 (Infinity) | 20 | 10/0 (Infinity) | 20 | 10/0 (Infinity) | 20 |
| Anorexia | 10/13 (76.9%) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 | 10/0 (Infinity) | 28 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 7/13 (53.8%) | 8 | 7/0 (Infinity) | 8 | 7/0 (Infinity) | 8 | 7/0 (Infinity) | 8 | 7/0 (Infinity) | 8 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Ana De Jesus-Acosta |
|---|---|
| Organization | Johns Hopkins University School of Medicine |
| Phone | 443-287-0411 |
| adejesu1@jhmi.edu |
- J1130
- NA_00047491