Histologically or Cytologically Confirmed Pancreatic CaPhase 1NCT01294358

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

A Phase 1 study testing Gemcitabine in people with Histologically or Cytologically Confirmed Pancreatic Ca and Unresectable or Borderline Resectable Pancreatic Ca, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Background: Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink some of the tumor, but even with chemotherapy only about 25 percent of patients will live for 1 year following diagnosis. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Histologically or Cytologically Confirmed Pancreatic Ca, Unresectable or Borderline Resectable Pancreatic Ca
What is being tested?: Gemcitabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 26 Jan 2011to 23 Jul 2014
Phase: Phase 1
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 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically or cytologically confirmed locally advanced pancreatic adenocarcinoma or clinical and radiographic evidence of pancreatic cancer
Note: Patients with a limited disease burden outside the pancreas, who have undergone systemic chemotherapy for metastatic disease and have achieved a complete response on the metastatic lesions of greater than or equal to 6 months, and have no evidence of disease outside the pancreas at time of enrollment, are eligible.
Disease must be evaluable
Disease should be deemed unresectable by the MD Anderson criteria
Patients may be chemo naive or have received prior chemotherapy (including Gemcitabine) and/or radiation
Greater than or equal to 18 years of age

Show all 20Show fewer

Must be able to understand and sign the Informed Consent Document
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or equal to 2
Life expectancy of greater than three months
Patients of both genders must be willing to practice birth control during and for four months after receiving chemotherapy
Hematology:
Absolute neutrophil count greater than 1300/mm(3) without the support of Filgrastim.
Platelet count greater than 75,000/mm(3).
Hemoglobin greater than 8.0 g/dl.
Chemistry:
Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 3 times the upper limit of normal, unless patient carries a biliary stent. For these patients, to account for asymptomatic, transient elevations in transaminases ('transaminitis'), serum ALT/AST may be less than or equal to 5 times the upper limit of normal provided all other eligibility parameters are met.
Serum creatinine less than or equal to 1.8 mg/dl unless the measured creatinine clearance is greater than 60 mL/min/1.73 m(2)
Total bilirubin less than or equal to 2 mg/dl,
Prothrombin time (PT) within 2 seconds of the upper limit of normal or International Normalized Ratio (INR) less than or equal to 1.8
No history of prior/other malignancies within the 2 years prior to enrollment with the exception of basal cell carcinoma

Who cannot join

Metastatic disease including malignant ascites
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure
Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies
Weight less than 40 kg
Significant ascites, greater than 1000cc in the absence of peritoneal disease

Show all 9Show fewer

Concomitant medical problems that would place the patient at an unacceptable risk for the procedure
Need for concurrent chemotherapy
Discretion of the principal investigator (PI)

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink some of the tumor, but even with chemotherapy only about 25 percent of patients will live for 1 year following diagnosis. Several preliminary studies have shown that it is safe to give chemotherapy directly into the pancreas in the area of the tumor, and that giving gemcitabine over a longer period increases the amount of drug that is available to the tumor. Researchers are interested in studying whether giving the approved pancreatic cancer chemotherapy drug gemcitabine directly into the pancreas in the area of the cancer and at a slow rate of infusion is a safe and effective treatment.

Objectives:

To test the safety and effectiveness of administering gemcitabine directly to a pancreatic tumor at a slow rate of infusion.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with pancreatic cancer that is currently too large to be removed surgically but has not yet spread to other organs.

Design:

Participants will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies.
Participants will undergo pancreatic angiography and embolization, during which a catheter will be threaded into the blood vessels near the pancreas and a contrast dye will be used to show the blood vessels supplying the tumor. These blood vessels will then be surgically closed off.
After the embolization, gemcitabine will be given as an infusion into the area around the tumor over 24 hours.
Participants will return to the clinical center every 2 weeks after the first infusion for additional infusions of gemcitabine, using the same procedures as above. Participants will be monitored with frequent blood tests and imaging studies.
Two weeks after the fourth treatment (course 1), participants will have more imaging studies, a physical examination, and blood tests. If the tumor is shrinking, participants will have two more courses of treatment (eight more infusions of gemcitabine).
Participants will have followup visits every 3 months for 2 years following the last treatment and then every 6 months.

Read the detailed description

Background:

Pancreatic cancer is the fourth leading cause of cancer death in the United States.
Surgery offers the only chance at cure; however, less than 20% of patients are considered resectable at initial presentation.
A common reason for being classified as unresectable is loco-regional advanced disease.
Several phase I studies of regional administration of chemotherapy have proven safe.
The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is achievement of higher local bio-available active drug levels at the tumor bed.
The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a phase I trial offering highly selective 24-hour intra-arterial administration of Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced pancreatic cancer.

Objectives:

Primary Objective:

To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose limiting toxicity (DLT)).
To establish the maximum tolerated dose (MTD)

Secondary Objectives:

To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT) perfusion criteria (European Association for the Study of the Liver (EASL))
To determine progression free and overall survival.
To evaluate the conversion rate from unresectable or borderline resectable to potentially resectable pancreatic cancer.
To determine progression-free and overall survival.
To analyze potential selection criteria to be used in future studies for patients who present with marginally unresectable or unresectable locally-advanced pancreatic cancer that might benefit from this approach.

Eligibility:

Unresectable locally-advanced pancreatic cancer.
18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2
Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.
No extra-pancreatic disease except regional lymph nodes.

Design:

This is a dose escalation phase-I study.
Patients considered unresectable due to locally-advanced pancreatic cancer will receive selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling port.
Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles.
Three to six patients will be enrolled per dose cohort.
18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no progressive disease (PD), patients will continue up to 6 cycles.
Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy including gemcitabine will be allowed, as this mode of administration has better bioavailability, offer potential for better biological effect and less systemic toxicity profiles.

Conditions: Histologically or Cytologically Confirmed Pancreatic Ca, Unresectable or Borderline Resectable Pancreatic Ca
Being tested: Gemcitabine
Keywords: Pancreatic Cancer, Regional Therapy, Selective Arterial Infusion, Locally Advanced Disease
Medical subject headings: Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GemcitabineDrug
Also called Gemzar
Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.

Study groups in NCT01294358
Study group	Role	What they receive
Gemcitabine Dose Escalation	Experimental	gemcitabine dose escalation Receives: Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicity (DLT )
Here is the number of participants with DLT. DLT is defined as follows: All grade 3 or greater toxicities with the exception of Grade 3 constitutional symptoms that persist for less than 72 hours, Grade 3 and 4 myelosuppression (neutrophils and thrombocytopenia) of less than 5 days duration. Grade 3 metabolic/laboratory events that are correctable within 24 hours. Events that are assessed by the principal investigator as clearly unrelated to the agent will not be considered DLTs (e.g., events directly related to catheter insertion, pain related to underlying disease).
Measured: Cycle 1 (4 weeks), for up to 6 cycles
MTD (Maximum Tolerated Dose)
The MTD is the highest dose that induces dose limiting toxicity (DLT) in no more than 2 patients among a cohort of 6 patients. If 1 or fewer patients experience dose limiting toxicity than the dose level will define the MTD. Only DLT's that occurred during cycle 1 of each dose level were used to determine the MTD.
Measured: Cycle 1 (4 weeks), for up to 6 cycles

Secondary outcomes (9)

Response Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Measured: Every 2 cycles (8 weeks), up to 18 weeks
Response Rate Using Positron Emission Tomography (PET)
Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Measured: Every 2 cycles (8 weeks), up to 18 weeks
Response Rate Using Magnetic Resonance Imaging (MRI)
Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Measured: Every 2 cycles (8 weeks), up to 18 weeks
Response Using Computed Tomography (CT) Perfusion Criteria European Association for the Study of the Liver (EASL1)
Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Measured: Every 2 cycles (8 weeks), up to 18 weeks
Median Time to Progression
Time to progression is the time between the first day of treatment to the day of disease progression. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.
Measured: From first day of treatment to the day of progression, assessed up to 221 months
Median Overall Survival (OS)
Overall survival is defined as the time between the first day of treatment to the day of death.
Measured: Overall survival was assessed through study completion, an average of 3 years.
Number of Participants Who Converted From Unresectable or Borderline Resectable To Potentially Resectable Pancreatic Cancer
Resectability is defined by the MD Anderson Resectability criteria: Resectable is no extension; normal fat plane between the tumor and the artery (superior mesenteric artery (SMA)). No extension (celiac axis/hepatic artery). Patent (superior mesenteric vein/portal vein (SMV/PV)). Borderline resectable is tumor abutment ≤180◦ (one half or less) of the circumference of the artery; periarterial stranding and tumor points of contact forming a convexity against the vessel improve chances of resection (SMA). Short-segment encasement/abutment of the common hepatic artery (typically at the gastroduodenal origin) (celiac axis/hepatic artery). Short-segment occlusion with suitable vessel above and below (SMV/PV). Locally advanced is encased (>180◦) (SMA). Encased and no technical option for reconstruction usually because of extension to the celiac axis/splenic/left gastric junction or the celiac origin (celiac axis/hepatic artery). Occluded and no technical option for reconstruction (SMV/PV).
Measured: 4 months
Number of Potential Selection Criteria to Be Used in Future Studies for Patients With Marginally Unresectable Or Unresectable Locally-Advanced Pancreatic Cancer
Number of selection criteria that can be used for unresectable pancreatic cancer.
Measured: up to 2.5 years
Number of Participants With Serious and Non-Serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned
Measured: Date treatment consent signed to date off study, approximately 2 years and 2 months and 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Jan 201123 Jul 2014

First posted11 Feb 2011 (estimated)
Study start26 Jan 2011
Primary completion23 Jul 2014
Study completion23 Jul 2014

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 (4)Papers the sponsor has linked to this study.
Other trials for Histologically or Cytologically Confirmed Pancreatic CaStudies 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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01294358
Sponsor's protocol ID: 110099
Other IDs: 11-C-0099, P10764
Status last verified: Nov 2019
First submitted: 10 Feb 2011
Last updated: 13 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep;35(3):421-30. doi: 10.1016/s0168-8278(01)00130-1. No abstract available.
PubMed 11592607
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
PubMed 19474385
Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999 Jul;189(1):1-7. doi: 10.1016/s1072-7515(99)00075-7.
PubMed 10401733
Davis JL, Pandalai P, Ripley RT, Langan RC, Steinberg SM, Walker M, Toomey MA, Levy E, Avital I. Regional chemotherapy in locally advanced pancreatic cancer: RECLAP trial. Trials. 2011 May 19;12:129. doi: 10.1186/1745-6215-12-129.
PubMed 21595953

Study at a glance

From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial
ClinicalTrials.gov ID: NCT01294358
Acronym / sponsor ID: 110099
Conditions: Histologically or Cytologically Confirmed Pancreatic Ca, Unresectable or Borderline Resectable Pancreatic Ca
Keywords: Pancreatic Cancer, Regional Therapy, Selective Arterial Infusion, Locally Advanced Disease
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 26 Jan 2011 (actual)
Primary completion: 23 Jul 2014 (actual)
Study completion: 23 Jul 2014 (actual)
First posted: 11 Feb 2011 (estimated)
Results: Posted 1 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink some of the tumor, but even with chemotherapy only about 25 percent of patients will live for 1 year following diagnosis. Several preliminary studies have shown that it is safe to give chemotherapy directly into the pancreas in the area of the tumor, and that giving gemcitabine over a longer period increases the amount of drug that is available to the tumor. Researchers are interested in studying whether giving the approved pancreatic cancer chemotherapy drug gemcitabine directly into the pancreas in the area of the cancer and at a slow rate of infusion is a safe and effective treatment.

Objectives:

To test the safety and effectiveness of administering gemcitabine directly to a pancreatic tumor at a slow rate of infusion.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with pancreatic cancer that is currently too large to be removed surgically but has not yet spread to other organs.

Design:

Participants will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies.
Participants will undergo pancreatic angiography and embolization, during which a catheter will be threaded into the blood vessels near the pancreas and a contrast dye will be used to show the blood vessels supplying the tumor. These blood vessels will then be surgically closed off.
After the embolization, gemcitabine will be given as an infusion into the area around the tumor over 24 hours.
Participants will return to the clinical center every 2 weeks after the first infusion for additional infusions of gemcitabine, using the same procedures as above. Participants will be monitored with frequent blood tests and imaging studies.
Two weeks after the fourth treatment (course 1), participants will have more imaging studies, a physical examination, and blood tests. If the tumor is shrinking, participants will have two more courses of treatment (eight more infusions of gemcitabine).
Participants will have followup visits every 3 months for 2 years following the last treatment and then every 6 months.

Detailed description

Background:

Pancreatic cancer is the fourth leading cause of cancer death in the United States.
Surgery offers the only chance at cure; however, less than 20% of patients are considered resectable at initial presentation.
A common reason for being classified as unresectable is loco-regional advanced disease.
Several phase I studies of regional administration of chemotherapy have proven safe.
The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is achievement of higher local bio-available active drug levels at the tumor bed.
The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a phase I trial offering highly selective 24-hour intra-arterial administration of Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced pancreatic cancer.

Objectives:

Primary Objective:

To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose limiting toxicity (DLT)).
To establish the maximum tolerated dose (MTD)

Secondary Objectives:

To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT) perfusion criteria (European Association for the Study of the Liver (EASL))
To determine progression free and overall survival.
To evaluate the conversion rate from unresectable or borderline resectable to potentially resectable pancreatic cancer.
To determine progression-free and overall survival.
To analyze potential selection criteria to be used in future studies for patients who present with marginally unresectable or unresectable locally-advanced pancreatic cancer that might benefit from this approach.

Eligibility:

Unresectable locally-advanced pancreatic cancer.
18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2
Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.
No extra-pancreatic disease except regional lymph nodes.

Design:

This is a dose escalation phase-I study.
Patients considered unresectable due to locally-advanced pancreatic cancer will receive selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling port.
Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles.
Three to six patients will be enrolled per dose cohort.
18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no progressive disease (PD), patients will continue up to 6 cycles.
Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy including gemcitabine will be allowed, as this mode of administration has better bioavailability, offer potential for better biological effect and less systemic toxicity profiles.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Gemcitabine Dose Escalation	Experimental	Drug: Gemcitabinegemcitabine dose escalation

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

Histologically or cytologically confirmed locally advanced pancreatic adenocarcinoma or clinical and radiographic evidence of pancreatic cancer
Note: Patients with a limited disease burden outside the pancreas, who have undergone systemic chemotherapy for metastatic disease and have achieved a complete response on the metastatic lesions of greater than or equal to 6 months, and have no evidence of disease outside the pancreas at time of enrollment, are eligible.
Disease must be evaluable
Disease should be deemed unresectable by the MD Anderson criteria
Patients may be chemo naive or have received prior chemotherapy (including Gemcitabine) and/or radiation

Key exclusion criteria (9 listed)

Metastatic disease including malignant ascites
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure
Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies
Weight less than 40 kg

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
GemcitabineAlso: GemzarGemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.	Drug	Gemcitabine Dose Escalation

Primary outcome

Number of Participants With Dose Limiting Toxicity (DLT )
Time frame: Cycle 1 (4 weeks), for up to 6 cycles
Here is the number of participants with DLT. DLT is defined as follows: All grade 3 or greater toxicities with the exception of Grade 3 constitutional symptoms that persist for less than 72 hours, Grade 3 and 4 myelosuppression (neutrophils and thrombocytopenia) of less than 5 days duration. Grade 3 metabolic/laboratory events that are correctable within 24 hours. Events that are assessed by the principal investigator as clearly unrelated to the agent will not be considered DLTs (e.g., events directly related to catheter insertion, pain related to underlying disease).
MTD (Maximum Tolerated Dose)
Time frame: Cycle 1 (4 weeks), for up to 6 cycles
The MTD is the highest dose that induces dose limiting toxicity (DLT) in no more than 2 patients among a cohort of 6 patients. If 1 or fewer patients experience dose limiting toxicity than the dose level will define the MTD. Only DLT's that occurred during cycle 1 of each dose level were used to determine the MTD.

9 secondary outcomes

Response Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Every 2 cycles (8 weeks), up to 18 weeks
Response Rate Using Positron Emission Tomography (PET)
Time frame: Every 2 cycles (8 weeks), up to 18 weeks
Response Rate Using Magnetic Resonance Imaging (MRI)
Time frame: Every 2 cycles (8 weeks), up to 18 weeks
Response Using Computed Tomography (CT) Perfusion Criteria European Association for the Study of the Liver (EASL1)
Time frame: Every 2 cycles (8 weeks), up to 18 weeks
Median Time to Progression
Time frame: From first day of treatment to the day of progression, assessed up to 221 months
Median Overall Survival (OS)
Time frame: Overall survival was assessed through study completion, an average of 3 years.
Number of Participants Who Converted From Unresectable or Borderline Resectable To Potentially Resectable Pancreatic Cancer
Time frame: 4 months
Number of Potential Selection Criteria to Be Used in Future Studies for Patients With Marginally Unresectable Or Unresectable Locally-Advanced Pancreatic Cancer
Time frame: up to 2.5 years
Number of Participants With Serious and Non-Serious Adverse Events
Time frame: Date treatment consent signed to date off study, approximately 2 years and 2 months and 21 days

Results and safety

Results posted to the registry on 1 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
18 mg/m(2)/24h	4	4
36 mg/m(2)/24h	0	0
72 mg/m(2)/24h	0	0
96 mg/m(2)/24h	0	0
115 mg/m(2)/24h.	0	0

Primary outcome: Number of Participants With Dose Limiting Toxicity (DLT )

Time frame: Cycle 1 (4 weeks), for up to 6 cycles. Count of participants. Unit: Participants

Measure	18 mg/m(2)/24h n = 4	36 mg/m(2)/24h n = 6	72 mg/m(2)/24h n = 4	96 mg/m(2)/24h n = 2	115 mg/m(2)/24h n = 1
Value	0	1	0	0	0

Primary outcome: MTD (Maximum Tolerated Dose)

Time frame: Cycle 1 (4 weeks), for up to 6 cycles. Number. Unit: mg/ml/24h

Measure	Gemcitabine Dose Escalation n = 6
Value	115

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Date treatment consent signed to date off study, approximately years, 2 months and 21 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
18 mg/m(2)/24h	0 of 4 (0%)	3 of 4 (75%)	0 of 4
36 mg/m(2)/24h	1 of 6 (16.7%)	5 of 6 (83.3%)	2 of 6
72 mg/m(2)/24h	0 of 4 (0%)	2 of 4 (50%)	2 of 4
96 mg/m(2)/24h.	2 of 2 (100%)	1 of 2 (50%)	1 of 2
115 mg/m(2)/24h	1 of 1 (100%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 11592607Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep;35(3):421-30. doi: 10.1016/s0168-8278(01)00130-1. No abstract available.
Background: PubMed 19474385Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
Background: PubMed 10401733Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999 Jul;189(1):1-7. doi: 10.1016/s1072-7515(99)00075-7.
Derived from this study: PubMed 21595953Davis JL, Pandalai P, Ripley RT, Langan RC, Steinberg SM, Walker M, Toomey MA, Levy E, Avital I. Regional chemotherapy in locally advanced pancreatic cancer: RECLAP trial. Trials. 2011 May 19;12:129. doi: 10.1186/1745-6215-12-129.
Individual participant dataSharing planned: No

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.

Udo Rudloff, M.D. principal investigator

National Cancer Institute (NCI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 20 inclusion and 9 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 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 1 Oct 2018). 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?

Number of Participants With Dose Limiting Toxicity (DLT ) (time frame: Cycle 1 (4 weeks), for up to 6 cycles). The study lists 2 primary outcomes in all. 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 NCT01294358, which also lists 4 linked publications.

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 13 Nov 2019.