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Paclitaxel

Gemcitabine

Capecitabine

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Antimetabolites

nab-Paclitaxel 125 mg/m2 intravenous (IV) infusion over approximately 30 to 45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle Subjects who complete 6 cycles of nab-paclitaxel and gemcitabine without disease progression or unacceptable toxicities, the Investigator will then determine the best option for the subject.

* Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR
* Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR
* Surgical intervention

nab-Paclitaxel

Chemoradiation

Surgery

Teng Jin Ong, MD

This clinical study is in subjects who are 18 years old or older with locally advanced pancreatic cancer who have not received prior treatment for their pancreatic cancer. The study treats all subjects with nab-Paclitaxel plus gemcitabine for approximately 6 months of treatment. Subjects who complete the treatment will choose, with their treating physicians, what additional treatment should be given: more nab-Paclitaxel plus gemcitabine, Chemoradiation therapy, or surgery to treat the locally advanced pancreatic cancer.

This is an international, non-randomized, open-label, multi-center, Phase 2 study in subjects who are 18 years old or older with locally advanced pancreatic cancer who have not received prior treatment for their pancreatic cancer. All subjects will be treated with nab-paclitaxel plus gemcitabine for 6 cycles followed by an Investigator's Choice of continuation of treatment with nab-paclitaxel plus gemcitabine, chemoradiation therapy, or surgery.

Safety assessments by laboratory testing and physical exams will be conducted through-out the study.

Efficacy assessments by physical exam will be preformed through-out the study and tumor imaging will be conducted approximately every 2 months.

Subjects will be considered active study participants from enrollment up to, but not including, survival follow-up period.

Phase 2 Nab® -Paclitaxel (Abraxane®) Plus Gemcitabine in Subjects With Locally Advanced Pancreatic Cancer (LAPC)

Nab-paclitaxel (Abraxane) Plus Gemcitabine in Subjects With Locally Advanced Pancreatic Cancer (LAPC): An International, Open-label, Multi-center, Phase 2 Study (LAPACT).

TTF was defined as the time after the first dose of study therapy to discontinuation of study therapy due to disease progression, death by any cause, or the start of a new non-protocol-defined anticancer therapy/surgery. If a participant does not progress, die or start a new non-protocol-defined anticancer therapy, the participant was censored on the last tumor assessment date.

Tumor evaluations of CT or MRI scans were assessed by the investigative sites and response determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1.

The definition for progressive disease (PD) was \>= 20% increase in the sum of diameters of target lesions from nadir, and the sum showed an absolute increase of \>= 5 mm; the progression of a non-target lesion or the appearance of any new lesions is also considered progression.

Median and its 90% confidence interval (CI) of TTF were estimated using the method of Brookmeyer and Crowley.

DCR was defined as the percentage of participants with a CR or PR or SD from of date of first treatment to 16 weeks. Tumor assessments after start of non-protocol-defined anticancer therapy were excluded.

RECIST 1.1 Definition:

* CR: disappearance of all target and non-target lesions; any pathological lymph nodes (target or non-target) must have reduction in short axis to \< 10 mm and no new lesions diagnosed.
* PR: a \>= 30% decrease in the sum of diameters of target lesions from baseline; no evidence of progression in any of the non-target lesions diagnosed at baseline; and no new lesions diagnosed.
* SD: neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for PD.

The two-sided 90% binomial confidence intervals (CIs) were estimated by Wilson score method.

ORR was defined as the percentage of participants that achieved a combined incidence of complete (CR) and partial response (PR) using RECIST 1.1 guidelines as assessed by the investigator. Assessments after new non-protocol-defined anticancer therapy are excluded. For participants who had resectable surgery in Investigator Choice period, assessments after surgical intervention are excluded.

RECIST 1.1 Definition:

* CR: disappearance of all target and non-target lesions; any pathological lymph nodes (target or non-target) must have reduction in short axis to \< 10 mm and no new lesions diagnosed.
* PR: a \>= 30% decrease in the sum of diameters of target lesions from baseline; no evidence of progression in any of the non-target lesions diagnosed at baseline; and no new lesions diagnosed.

The two-sided 90% binomial confidence intervals (CIs) were estimated by Wilson score method

Progression-free Survival (PFS) was defined as the time from the date of the first dose to the date of disease progression or death (by any cause), whichever is earlier. The analysis day was calculated from enrollment date for one participant who was not treated. Participants who have no disease progression or have not died were censored to last tumor assessment date with progression-free.

The definition for progressive disease (PD) was at least a 20% increase in the sum of diameters of target lesions from nadir; the sum must also demonstrate an absolute increase of \>= 5 mm; the progression of a non-target lesion or the appearance of any new lesions is also considered progression.

Median and its 90% confidence interval of PFS were estimated using the method of Brookmeyer and Crowley.

Overall survival was defined as the time from the date of first dose of study therapy to the date of death (by any cause). Participants who were alive at the end of study or clinical data cut were censored on the last known time that the participant was alive or the clinical cutoff date, whichever was earlier. Median and its 90% confidence interval of OS were estimated using the method of Brookmeyer and Crowley

The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) is a validated health-related quality of life (HRQoL) measure. The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures, including 5 functional scales, 3 symptom scales, 6 single symptom items, and 1 global health status / quality of life scale. No item occurs in more than one scale. All reported measures are transformed to a 0 - 100 scale. In the Global Health Status and 5 functional scales, 0 = worst possible quality of life/health status and 100 = best possible quality of life/health status. The best score on treatment is the best score from all post-baseline visits and is compared to the baseline to get the following responder categories. Responder categories: - Improved: \>=10 increase from baseline - Stable: neither increase nor decrease \>10 - Worsened: \>=10 decrease from baseline

The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) is a validated health-related quality of life (HRQoL) measure. The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures, including 5 functional scales, 3 symptom scales, 6 single symptom items, and 1 global health status / quality of life scale. No item occurs in more than one scale. All reported measures are transformed to a 0 to 100 scale. In the symptom scales and single symptom items, 0 = optimal health state and 100 = worst possible health state. The best score on treatment is the best score from all post-baseline visits and is compared to the baseline to get the following responder categories. Responder categories: - Improved: \>=10 decrease from baseline - Stable: neither increase nor decrease \>10 - Worsened: \>=10 increase from baseline

The EORTC pancreatic cancer module is a validated tool intended for patients at all disease stages undergoing surgical resection, palliative surgical intervention, endoscopic palliation or palliative chemotherapy. The module includes 26 questions, organized into 7 scales and 10 individual item scores. All reported measures are transformed to a 0 to 100 scale. Six summary scales reported are: - Pancreatic Pain - Digestive Symptoms - Altered Bowel Habits - Hepatic Scale - Body Image - Sexuality Scores of 0 = optimal health state and 100 = worst possible health state. The best score on treatment is the best score from all post-baseline visits and is compared to the baseline. Responder categories: - Improved: \>=MID decrease from baseline - Stable: no increase or decrease \>MID - Worsened: \>=MID increase from baseline MID = half the baseline standard deviation

The EORTC pancreatic cancer module is a validated tool intended for patients at all disease stages undergoing surgical resection, palliative surgical intervention, endoscopic palliation or palliative chemotherapy. The module includes 26 questions, organized into 7 scales and 10 individual item scores. The summary scale for Satisfaction with Health Care is reported. All reported measures are transformed to a 0 to 100 scale. Scores of 0 = not satisfied, worst possible health state and 100 = extremely satisfied, best possible health state. The best score on treatment is the best score from all post-baseline visits and is compared to the baseline to get the following responder categories. Responder categories: - Improved: \>=MID increase from baseline - Stable: no increase or decrease \>MID - Worsened: \>=MID decrease from baseline MID = half the baseline standard deviation

The EORTC pancreatic cancer module is a validated tool intended for patients at all disease stages undergoing surgical resection, palliative surgical intervention, endoscopic palliation or palliative chemotherapy. The module includes 26 questions, organized into 7 scales and 10 individual item scores. The 10 individual item scores are reported. All reported measures are transformed to a 0 to 100 scale. Scores of 0 = best possible health state and 100 = worst possible health state. The best score on treatment is the best score from all post-baseline visits and is compared to the baseline to get the following responder categories. Responder categories: - Improved: \>=MID decrease from baseline - Stable: no increase or decrease \>MID - Worsened: \>=MID increase from baseline MID = half the baseline standard deviation

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).

Celgene

One participant was enrolled but not treated. The safety population consisted of participants who received at least one dose of nab-paclitaxel.

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Nab-Paclitaxel Plus Gemcitabine (Induction Period)

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Overall includes nab-Paclitaxel plus Gemcitabine treatment cycles during the Induction Period, as well as the subset of participants who continued the regimen during the Investigator Choice Period.

Nab-Paclitaxel Plus Gemcitabine (Overall)

In the Induction period, nab-paclitaxel 125 mg/m\^2 intravenous (IV) infusion was administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine without disease progression or unacceptable toxicities, the Investigator then determined the best option for the participant in the Investigator's Choice Period: - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention

Nab-Paclitaxel Plus Gemcitabine

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG performance status assesses how the disease affects the daily living activities of the participant and helps determine appropriate treatment and prognosis. - 0 = Fully Active (Most Favorable Activity); - 1 = Restricted activity but ambulatory; - 2 = Ambulatory but unable to carry out work activities; - 3 = Limited Self-Care; - 4 = Completely Disabled.

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 0 = None or no neuromotor or neurosensory loss; 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

Baseline Albumin

Serum CA 19-9 concentrations may be elevated in patients with gastrointestinal malignancies such as pancreatic cancer.

Baseline CA19-9 measures are missing for six participants.

Carbohydrate Antigen 19-9 (CA19-9)

Neutrophil to lymphocyte ratio (NLR) is used as a marker of subclinical inflammation. Increased NLR is associated with poor prognosis in advanced pancreatic cancer.

Baseline Neutrophil - to - Lymphocyte Ratio (NLR)

Sum of Longest Diameter of Target Lesions

Number of Target Lesions

Time from Primary Diagnosis to First Dose

Intent-to-treat (ITT) population at start of Induction

Anne McClain, Senior Manager

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine without disease progression or unacceptable toxicities, the Investigator then determined the best option for the participant in the Investigator's Choice Period. - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention

Intent to treat population was defined as all participants enrolled into the study.

Kaplan-Meier Estimates for Time to Treatment Failure (TTF)

Disease Control Rate (DCR): Percentage of Participants With Complete (CR) or Partial Response (PR), or Stable Disease (SD) for ≥ 16 Weeks According to RECIST Version 1.1

Intent to treat population was defined as all participants who were enrolled into the study.

Overall Response Rate (ORR): Percentage of Participants With Complete (CR) or Partial Response (PR) According to RECIST Version 1.1

Kaplan-Meier Estimate of Progression-Free Survival (PFS)

Kaplan-Meier Estimates for Overall Survival (OS)

Global Health Status: Improved

Global Health Status: Stable

Global Health Status: Worsened

Physical Functioning Scale: Improved

Physical Functioning Scale: Stable

Physical Functioning Scale: Worsened

Role Functioning Scale: Improved

Role Functioning Scale: Stable

Role Functioning Scale: Worsened

Emotional Functioning Scale: Improved

Emotional Functioning Scale: Stable

Emotional Functioning Scale: Worsened

Cognitive Functioning Scale: Improved

Cognitive Functioning Scale: Stable

Cognitive Functioning Scale: Worsened

Social Functioning Scale: Improved

Social Functioning Scale: Stable

Social Functioning Scale: Worsened

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine the Investigator then determined the best option for the participant in the Investigator's Choice Period. - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention

Intent to treat population was defined as all participants enrolled into the study with both baseline and post baseline values.

Participant Counts in Response Categories Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): Global Health Status and 5 Functioning Scales

Symptom Scale-Fatigue: Improved

Symptom Scale-Fatigue: Stable

Symptom Scale-Fatigue: Worsened

Scale-Nausea+Vomiting: Improved

Scale-Nausea+Vomiting: Stable

Scale-Nausea+Vomiting: Worsened

Symptom Scale-Pain: Improved

Symptom Scale-Pain: Stable

Symptom Scale-Pain: Worsened

Symptom - Dyspnoea: Improved

Symptom - Dyspnoea: Stable

Symptom - Dyspnoea: Worsened

Symptom - Insomnia: Improved

Symptom - Insomnia: Stable

Symptom - Insomnia: Worsened

Symptom - Appetite loss: Improved

Symptom - Appetite loss: Stable

Symptom - Appetite loss: Worsened

Symptom - Constipation: Improved

Symptom - Constipation: Stable

Symptom - Constipation: Worsened

Symptom - Diarrhoea: Improved

Symptom - Diarrhoea: Stable

Symptom - Diarrhoea: Worsened

Symptom - Financial difficulties: Improved

Symptom - Financial difficulties: stable:

Symptom - Financial difficulties: Worsened

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine, the Investigator then determined the best option for the participant in the Investigator's Choice Period. - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention

Participant Counts in Response Categories Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): Symptom Scales and Single Symptom Items

Pancreatic Pain Scale: Improved

Pancreatic Pain Scale: Stable

Pancreatic Pain Scale: Worsened

Digestive Symptom Scale: Improved

Digestive Symptom Scale: Stable

Digestive Symptom Scale: Worsened

Altered Bowel Habits Scale: Improved

Altered Bowel Habits Scale: Stable

Altered Bowel Habits Scale: Worsened

Hepatic Scale: Improved

Hepatic Scale: Stable

Hepatic Scale: Worsened

Body Image Scale: Improved

Body Image Scale: Stable

Body Image Scale: Worsened

Sexuality Scale: Improved

Sexuality Scale: Stable

Sexuality Scale: Worsened

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine the Investigator then determined the best option for the participant in the Investigator's Choice Period. - Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR - Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR - Surgical intervention

Participant Counts in Response Categories Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire For Pancreatic Cancer (EORTC-QLQ PAN26): Six Summary Scales

Satisfaction with Health Care Scale: Improved

Satisfaction with Health Care Scale: Stable

Satisfaction with Health Care Scale: Worsened

Participant Counts in Response Categories Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire For Pancreatic Cancer (EORTC-QLQ PAN26): Satisfaction With Health Care Scale

Abdominal Bloating: Improved

Abdominal Bloating: Stable

Abdominal Bloating: Worsened

Taste Changes: Improved

Taste Changes: Stable

Taste Changes: Worsened

Indigestion: Improved

Indigestion: Stable

Indigestion: Worsened

Flatulence: Improved

Flatulence: Stable

Flatulence: Worsened

Weight Loss: Improved

Weight Loss: Stable

Weight Loss: Worsened

Limb Weakness: Improved

Limb Weakness: Stable

Limb Weakness: Worsened

Dry Mouth: Improved

Dry Mouth: Stable

Dry Mouth: Worsened

Treatment Side-Effects: Improved

Treatment Side-Effects: Stable

Treatment Side-Effects: Worsened

Worry About Future Health: Improved

Worry About Future Health: Stable

Worry About Future Health: Worsened

Limits on Activity Planning: Improved

Limits on Activity Planning: Stable

Limits on Activity Planning: Worsened

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. For participants who completed 6 cycles of nab-paclitaxel and gemcitabine without disease progression or unacceptable toxicities, the Investigator then determined the best option for the participant in the Investigator's Choice Period.

Participant Counts in Response Categories Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire For Pancreatic Cancer (EORTC-QLQ PAN26): 10 Individual Item Scores

>= 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 related serious TEAE

>=1 TEAE leading to discontinuation of IP

>=1 related TEAE leading to discontinuation of IP

>=1 TEAE leading to dose reduction of IP

>=1 related TEAE leading to dose reduction of IP

>=1 TEAE leading to interruption of IP

>=1 related TEAE leading to interruption of IP

>= TEAE leading to death

>=1 related TEAE leading to death

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Six treatment cycles were planned.

nab-Paclitaxel 125 mg/m\^2 intravenous (IV) infusion administered over approximately 30-45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m\^2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Overall includes nab-Paclitaxel plus Gemcitabine treatment cycles during the Induction Period, as well as the subset of participants who continued the regimen during the Investigator Choice Period.

The Treated population consists of all participants who received at least 1 dose of nab-paclitaxel or gemcitabine.

Participants With Treatment Emergent Adverse Events (TEAEs)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 2 Nab® -Paclitaxel (Abraxane®) Plus Gemcitabine in Subjects With Locally Advanced Pancreatic Cancer (LAPC)	NCT02301143	Pancreatic Neop...	nab-Paclitaxel Gemcitabine Chemoradiation Capecitabine Surgery	18 Years -	Celgene
Phase 2 Nab® -Paclitaxel (Abraxane®) Plus Gemcitabine in Subjects With Locally Advanced Pancreatic Cancer (LAPC)	NCT02301143	Pancreatic Neop...	nab-Paclitaxel Gemcitabine Chemoradiation Capecitabine Surgery	18 Years -	Celgene

Spots Global Cancer Trial Database for locally advanced pacriatic cancer