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

Pancreatic Neoplasms Clinical Trial

— LAPACT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301143
• Other study ID #: ABI-007-PANC-007
• Status: Completed
• Phase: Phase 2
• Start date: April 21, 2015
• Est. completion date: April 26, 2018

Study information

• Verified date: March 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: April 26, 2018
• Est. primary completion date: November 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Non- metastasis, unresectable, adenocarcinoma pancreatic cancer patients

• No prior anticancer therapy for pancreatic cancer

•= 18 years of age with a performance status of 0 or 1•Adequate complete blood counts, hepatic function, and renal function

• Signed informed Consent

Exclusion Criteria:

• Active bacterial, viral, or fungal infection

• Infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or receiving immunosuppressive or myelosuppressive

• Subjects with sensory neuropathy, ascites, or plastic biliary stent.

• Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders (including but not limited to connective tissue disorders, lung disease, and cardiac or seizure disorders)

• Women who are pregnant or breast feeding

Related Conditions & MeSH terms

• Pancreatic Neoplasms

Intervention

Drug:
• nab-Paclitaxel

• Gemcitabine

• Chemoradiation

• Capecitabine

Procedure:
• Surgery
Surgical intervention

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUM Hôpital Saint-Luc	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	Centre Regional de lutte contre le cancer Paul Papin	Angers
France	Centre Hospitalier Belfort Montbeliard	Besançon
France	CHRU Besancon	Besançon
France	Hopital Beaujon	Clichy cedex
France	Hopital Saint Antoine	Paris
France	Hopital Haut Leveque	Pessac Cedex
Italy	Ospedale Sacro Cuore di Gesu FatebeneFratelli	Benevento
Italy	Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Policlinico Universitario Campus Biomedico Di Roma	Roma
Spain	Hospital Universitario a Coruna	A Coruna
Spain	ICO-Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Miguel Servet	Zaragoza
United States	Saint Joseph Mercy Ann Arbor Hospital	Ann Arbor	Michigan
United States	Piedmont Cancer Institute PC	Atlanta	Georgia
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Montefiore Einstein Cancer Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Mark H Zangmeister Center	Columbus	Ohio
United States	Karmanos Cancer Center Wayne State University	Detroit	Michigan
United States	Houston Methodist Cancer Center	Houston	Texas
United States	Clinical Research Alliance	Lake Success	New York
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Regional Cancer Care Associates LLC	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Smilow Cancer Hospital At Yale-New Haven	New Haven	Connecticut
United States	Cancer Treatment Centers of America - Southeastern Regional Medical Center	Newnan	Georgia
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	UC Davis Cancer Center	Sacramento	California
United States	Scripps Clinic Torrey Pines	San Diego	California
United States	ME Center for Cancer Medicine	Scarborough	Maine
United States	Mayo Clinic - Arizona	Scottsdale	Arizona
United States	State University of New York Upstate Medical Center	Syracuse	New York
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimates for Time to Treatment Failure (TTF)	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.	Day 1 of study treatment up to 28.75 months; (maximum time for the last tumor assessment)
Secondary	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	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.	Day 1 of study treatment up to the end of investigator choice period plus 28 days; up to 76.9 weeks
Secondary	Overall Response Rate (ORR): Percentage of Participants With Complete (CR) or Partial Response (PR) According to RECIST Version 1.1	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	Day 1 of study treatment up to the end of investigator choice period plus 28 days; up to 76.9 weeks
Secondary	Kaplan-Meier Estimate of Progression-Free Survival (PFS)	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.	Day 1 of study treatment up to 28.75 months (maximum time for the last tumor assessment)
Secondary	Kaplan-Meier Estimates for Overall Survival (OS)	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	Day 1 of study treatment up to 31.34 months (maximum time for survival follow-up)
Secondary	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	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	Baseline (Day -1), Day 1 of each cycle, for up to 19 cycles each cycle consisting of 28 days and the 28-day follow-up visit
Secondary	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	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	Baseline (Day -1), Day 1 of each cycle, for up to 19 cycles each cycle consisting of 28 days and the 28-day follow-up visit
Secondary	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	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	Baseline (Day -1), Day 1 of each cycle, for up to 19 cycles each cycle consisting of 28 days and the 28-day follow-up visit
Secondary	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	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	Baseline (Day -1), Day 1 of each cycle, for up to 19 cycles each cycle consisting of 28 days and the 28-day follow-up visit
Secondary	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	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	Baseline (Day -1), Day 1 of each cycle, for up to 19 cycles each cycle consisting of 28 days and the 28-day follow-up visit
Secondary	Participants With Treatment Emergent Adverse Events (TEAEs)	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).	Day 1 of study drug up to end of the study; up to 31.3 months