Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Digestive System Neoplasms

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Participants received nab-Paclitaxel 125 mg/m\^2 administered as an intravenous (IV) infusion over 30 to 40 minutes, followed by gemcitabine 1000 mg/m\^2 as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, subject or physician decision, withdrawal of consent, or death.

Participants received gemcitabine 1000 mg/m\^2 administered as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, subject or physician decision, withdrawal of consent, or death.

nab-Paclitaxel 125 mg/m\^2 on Days 1, 8, and 15 of every 28 day treatment cycle by intravenous (IV) administration for a total of 6 cycles.

nab-Paclitaxel

Gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 of a 28 day cycle by IV administration for a total of 6 cycles.

Bristol-Myers Squibb

The purpose of this study is to compare whether there is a delay or prevention of recurrence or death in participants with surgically removed pancreatic cancer who then take nab-Paclitaxel in combination with gemcitabine compared to those who take gemcitabine alone.

ABI-007-PANC-003 is a Phase 3, international, multicenter, randomized, open-label, controlled study that will compare the efficacy of nab-paclitaxel in combination with gemcitabine to gemcitabine alone as adjuvant treatment for 6 cycles in patients with surgically resected pancreatic adenocarcinoma.

Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the "Apact" Study)

A Phase 3, Multicenter, Open-label, Randomized Study of Nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Subjects With Surgically Resected Pancreatic Adenocarcinoma

Disease free survival was defined as the time from the date of randomization to the date of disease recurrence or death, whichever occurred earlier. Disease recurrence was determined by the independent radiological review of computed tomography (CT) or magnetic resonance imaging (MRI) scans. Participants who did not have disease recurrence or did not die were censored at the last tumor assessment date with disease-free status or the randomization date if the last tumor assessment with disease-free status was missing. Disease-free status referred to a status that was neither being disease recurrent nor indeterminate or not evaluable. Participants who received new anti-cancer therapy or cancer-related surgery prior to disease recurrence or death were censored at the date of last tumor assessment with disease-free status prior to the start of new anti-cancer therapy or cancer-related surgery or the randomization date.

Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the end of study or clinical data cut were censored on the last-known-to-be-alive date or the clinical cutoff date, whichever was earlier.

TEAEs are defined as any adverse event (AE) that begin or worsen on or after the start of study drug or procedure of the study period through the maximum duration of the period plus 28 days. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study drug was determined by the investigator. A treatment-related TEAE is defined as TEAE which was considered to be related to one or both of the study drugs and reported as 'Suspected' on the case report form. AEs with a missing relationship were treated as 'treatment-related' in data summaries. IP (investigational product) refers to nab-Paclitaxel and/or Gemcitabine. "Related" TEAE refers to relation to study drug (IP).

The number of participants with grade 3-4 laboratory abnormalities in selected clinically significant parameters. Grades for chemistry parameters were coded using National Cancer Institute Common Terminology Criteria for Adverse Events (Grade 3= severe, Grade 4= life-threatening).

Celgene

The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Participants received nab-Paclitaxel 125 mg/m\^2 administered as an intravenous (IV) infusion over 30 to 40 minutes, followed by gemcitabine 1000 mg/m\^2 as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, participant or physician decision, withdrawal of consent, or death.

Nab-Paclitaxel and Gemcitabine

Participants received gemcitabine 1000 mg/m\^2 administered as an IV infusion over 30 to 40 minutes on Days 1, 8 and 15 of each 28-day treatment cycle for 6 cycles, unless there was evidence of radiologic disease recurrence, unacceptable toxicity, participant or physician decision, withdrawal of consent, or death.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Region of Enrollment

Body Surface Area (BSA)

ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: 0 = Fully active, no restrictions; 1 = Restricted activity but ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities; 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled, no self-care, confined to bed or chair; 5 = Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Physician assessment for grading of peripheral neuropathy in participants receiving chemotherapy according to National Cancer Institute Common Toxicity Criteria (NCICTC): - Grade 1 = Asymptomatic: loss of deep tendon reflexes or paresthesia; - Grade 2 = Moderate symptoms: limiting instrumental Activities of Daily Living (ADLs); - Grade 3 = Severe symptoms: limiting self-care ADL; assistance device indicated; - Grade 4 = Life-threatening consequences: urgent intervention indicated.

Physician Assessment of Peripheral Neuropathy

Time from Surgery to Randomization

The TNM system is the most widely used cancer staging system. Most hospitals and medical centers use the TNM system as their main method for cancer reporting. In the TNM system: The T refers to the size and extent of the main tumor. The main tumor is usually called the primary tumor and the "T" followed by a number shows the size of the tumor. The N refers to the number of nearby lymph nodes that have cancer. The M refers to whether the cancer has metastasized. This means that the cancer has spread from the primary tumor to other parts of the body.

TNM Classification

The nodal status refers to the N and includes the number of nearby lymph nodes that are positive or negative for cancer.

Nodal Status

Resection status was based on investigational site data (pathology reports were collected, but central pathology review and/or standardization was not conducted).

Resection Status

The Intent-to-treat (ITT) population consisted of all randomized participants regardless of whether the participant received any investigational product (IP) or had any efficacy assessments collected.

Bristol-Myers Squibb Study Director

The intent-to-treat population consisted of all randomized participants regardless of whether they received any investigational product (IP) or had any efficacy assessment collected.

Kaplan Meier Estimate for Disease Free Survival (DFS) According to the Independent Radiological Review Committee

25th Quartile

50th Quartile

75th Quartile

The intent-to-treat population consisted of all randomized participants regardless of whether the participant received any IP or had any efficacy assessment collected.

Kaplan Meier Estimate of Overall Survival (OS)

≥1 TEAE

≥1 Related TEAE

≥1 TEAE of Severity Grade 3 or Higher

≥ 1 Related TEAE of Severity Grade 3 or Higher

≥1 Serious TEAE

≥1 Serious Related TEAE

≥1 TEAE Leading to Withdrawal of IP

≥1 Related TEAE Leading to Withdrawal of IP

≥1 TEAE Lead Dose Reduction: nab-Paclitaxel or Gem

≥1 Related TEAE Dose Reduct: nab-Paclitaxel or Gem

TEAE Lead Dose Interruption nab-Paclitaxel or Gem

≥1 Related TEAE Dose Interruption to IP

TEAE Leading to Death

>=1 Related TEAE Leading to Death

Treated Population consisted of randomized participants who received at least one dose of study drug.

Number of Participants With Treatment Emergent Adverse Events (TEAE's)

Alkaline phosphatase

Alanine aminotransferase

Aspartate aminotransferase

Bilirubin

All treated participants with at least one post-baseline value and received at least one dose of investigational product (IP).

The Number of Participants With Clinical Chemistry Laboratory-Detected Abnormalities (Grade 3-4)

Pre-Treatment (Randomization) Period

Treatment Period

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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 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.

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.

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.

LDE225-600mg

Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.

Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.

nab-paclitaxel

Phase I: oral LDE225 (Sonidegib), 400mg daily.

LDE225-400mg

Phase I: oral LDE225 (Sonidegib), 800mg daily.

LDE225-800mg

Ana De Jesus-Acosta, MD

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.

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:

1. 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.
2. 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.

Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma

Phase 1/2 Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma.

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).

Number of participants with borderline resectable pancreatic adenocarcinoma (PDA) who undergo resection after therapy

Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first.

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.

Novartis Pharmaceuticals

The Skip Viragh Foundation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

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.

Phase I, Gem, Nab-paclitaxel, and 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.

Phase I, Gem, Nab-paclitaxel, and 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 I, Gem, Nab-paclitaxel, and 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 A: Gem, Nab-paclitaxel, and LDE 225

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.

Phase II, Arm B: Gemcitabine and Nab-paclitaxel

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.

Not Hispanic or Latino

All participants were enrolled in Phase 1, gem, nab-paclitaxel, and LDE225-600mg arm only. Other arms did not have any participants due to the study's early termination.

Dr. Ana De Jesus-Acosta

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.

Phase I: Gem, Nab-paclitaxel, and 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), 400 mg daily.

Phase I: Gem, Nab-paclitaxel, and 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), 800 mg daily.

Phase I: Gem, Nab-paclitaxel, and LDE225-800mg

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.

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

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.

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. 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.

Phase II-Arm B:Gem,Nab-paclitaxel

No data was collected to assess this outcome measure as the study was terminated before Phase II.

Phase II - Resection Rate of Two Preoperative Chemotherapy Regimens in Patients With Borderline Resectable PDA

Overall Survival

Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the "Apact" Study)	NCT01964430	Pancreatic Neop... Digestive Syste... Neoplasms by Si... Neoplasms Endocrine Gland... Pancreatic Dise... Digestive Syste... Endocrine Syste... Gemcitabine Antimetabolites...	nab-Paclitaxel Gemcitabine	18 Years -	Celgene
Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma	NCT01431794	Pancreatic Duct...	LDE225-600mg Gemcitabine nab-paclitaxel LDE225-400mg LDE225-800mg	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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