Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00735917
• Collaborator: (none)
• Enrollment: 19
• Locations: 9
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well saracatinib works in treating patients with previously treated metastatic pancreatic cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: saracatinib; Other: pharmacogenomic studies; Other: pharmacological study; Procedure: positron emission tomography; Radiation: fludeoxyglucose F 18; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the 6-month survival of biomarker-positive patients with previously treated metastatic pancreatic cancer receiving AZD0530 (saracatinib).

2. To determine the adverse events of this drug in these patients.

SECONDARY OBJECTIVES:

1. To evaluate the response rate in patients treated with this drug. II. To evaluate the overall survival of patients treated with this drug. III. To explore the pharmacodynamic effects of AZD0530 with optional tumor biopsies, pharmacokinetic studies, and positron emission tomography (PET) scans in a subset of patients.

OUTLINE:

Patients receive saracatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor therapy) Patients receive saracatinib PO QD on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: saracatinib; Given PO; Other Names: AZD0530 ; Other: pharmacogenomic studies; Optional correlative studies; Other Names: Pharmacogenomic Study ; Other: pharmacological study; Optional correlative studies; Other Names: pharmacological studies ; Procedure: positron emission tomography; Optional correlative studies; Other Names: FDG-PET PET PET scan tomography, emission computed ; Radiation: fludeoxyglucose F 18; Optional correlative studies; Other Names: 18FDG FDG ; Other: laboratory biomarker analysis; Optional correlative studies

Outcome Measures

Primary Outcome Measures

1. Six Month Survival [Up to 6 months]

   The proportion of successes will be estimated by the number of surviving participants at 6 months divided by the total number of evaluable patients. A confidence interval for the 6-month survival rate was calculated using the exact binomial method.

Secondary Outcome Measures

1. Overall Survival [Up to 2 years]

   Overall survival time is defined as the time from registration to death due to any cause. The median survival time and 95% confidence intervals will be estimated using the method of Kaplan-Meier.

2. Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR]) [Evaluated using the first 6 courses of treatment]

   A confirmed tumor response is defined to be a CR or PR noted as> the objective status on 2 consecutive evaluations at least 4 weeks apart. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)> > Complete Response (CR): Disappearance of all non-nodal target lesions and each target lymph node must have a reduction in short axis to <1.0 centimeters.> > Partial response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axes of the target lymph nodes taking as reference the baseline sum of diameters.

3. Duration of Response [From the date first objective status is noted to be either a CR or PR to the date progression is documented, assessed up to 2 years]

   Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Estimated by the method of Kaplan-Meier.

4. Progression-Free Survival [Progression and survival status assessed every month, up to 2 years]

   Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Metastatic disease

• Received ≥ 1 prior chemotherapy regimen, preferably gemcitabine hydrochloride-based

• Biomarker screening portion of study:

• For subjects without archival tissue available (core biopsy or resection specimen; fine-needle aspirate samples only are not sufficient), must be willing to undergo a fresh needle-core biopsy of a safely biopsiable metastasis

• No known brain metastases

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%

• White blood cell (WBC) ≥ 3,000/mm³

• Absolute neutrophil count (ANC) ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL

• Total bilirubin < 1.5 times upper normal limit (ULN) (patients may have been shunted in order to achieve normal bilirubin level)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 times ULN (< 5 times ULN for patients with liver metastases)

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Urine protein < 1,000 mg

• Urine protein: creatinine ratio ≤ 1.0

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Asymptomatic human immunodeficiency virus (HIV) allowed

• Willingness to undergo 2 tumor biopsies

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530

• No prolonged QTc interval (i.e., ≥ 480 msec)

• No other significant electrocardiogram (ECG) abnormalities

• No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 150 mm Hg or diastolic BP ≥ 90 mm Hg)

• No concurrent cardiac dysfunction including, but not limited to, any of the following:

• History of ischemic heart disease

• Myocardial infarction

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs ability to swallow AZD0530 tablets

• No uncontrolled concurrent illness including, but not limited to any of the following:

• Ongoing or active infection

• Psychiatric illness or social situations that would limit compliance with study requirements

• No other malignancy within the past 5 years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix

• Recovered from all prior therapy (< grade 2) (excluding alopecia) administered within the past 4 weeks

• At least 3 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin)

• At least 4 weeks since prior radiotherapy

• More than 7 days since prior and no concurrent cytochrome P450 3A4 (CYP3A4)-active agents

• No ongoing adverse events (excluding alopecia) due to chemotherapy or radiotherapy given more than 4 weeks prior to study

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

• Concurrent low molecular weight heparin or full-dose coumadin allowed

• Concurrent therapeutic hematopoietic growth factors allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	University of Colorado at Denver	Aurora	Colorado	United States	80045
3	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
4	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
7	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
8	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
9	National University Hospital	Singapore		Singapore	119074

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Wells Messersmith, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00735917
• Other Study ID Numbers: NCI-2009-00194; NCI-2009-00194; MAYO-MC0547; CDR0000610063; MC0547; 7602; P30CA015083; N01CM62205; NCT01647035
• First Posted: Aug 15, 2008
• Last Update Posted: Apr 2, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Pancreatic Neoplasms; Saracatinib; Fluorodeoxyglucose F18

Study Results

Participant Flow

Recruitment Details	Nineteen patients with gemcitabine-resistant metastatic pancreatic cancer were enrolled from four U.S. locations from October 2008 to January 2011.
Pre-assignment Detail	All 19 patients accrued to this study were used to report endpoints.

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Overall Participants	19
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	11 57.9%
Male	8 42.1%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Six Month Survival
Description	The proportion of successes will be estimated by the number of surviving participants at 6 months divided by the total number of evaluable patients. A confidence interval for the 6-month survival rate was calculated using the exact binomial method.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	19
Number (95% Confidence Interval) [percentage of patients]	11

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as the time from registration to death due to any cause. The median survival time and 95% confidence intervals will be estimated using the method of Kaplan-Meier.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	19
Median (95% Confidence Interval) [months]	2.5

3. Secondary Outcome

Title	Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR])
Description	A confirmed tumor response is defined to be a CR or PR noted as> the objective status on 2 consecutive evaluations at least 4 weeks apart. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)> > Complete Response (CR): Disappearance of all non-nodal target lesions and each target lymph node must have a reduction in short axis to <1.0 centimeters.> > Partial response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axes of the target lymph nodes taking as reference the baseline sum of diameters.
Time Frame	Evaluated using the first 6 courses of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	19
Number [participants]	0 0%

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Estimated by the method of Kaplan-Meier.
Time Frame	From the date first objective status is noted to be either a CR or PR to the date progression is documented, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

No patients qualified for a confirmed response and therefore this endpoint was not analyzed.

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

5. Secondary Outcome

Title	Progression-Free Survival
Description	Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.
Time Frame	Progression and survival status assessed every month, up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	19
Median (95% Confidence Interval) [months]	1.6

Adverse Events

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	13/19 (68.4%)
Blood and lymphatic system disorders
Hemoglobin decreased	3/19 (15.8%)	3
Thrombotic microangiopathy	1/19 (5.3%)	1
Gastrointestinal disorders
Abdominal pain	1/19 (5.3%)	1
Diarrhea	1/19 (5.3%)	1
Intra-abdominal hemorrhage	2/19 (10.5%)	2
Nausea	4/19 (21.1%)	4
Upper gastrointestinal hemorrhage	1/19 (5.3%)	1
Vomiting	4/19 (21.1%)	4
General disorders
Disease progression	2/19 (10.5%)	2
Fatigue	3/19 (15.8%)	3
Hepatobiliary disorders
Gallbladder perforation	1/19 (5.3%)	1
Infections and infestations
Biliary tract infection	1/19 (5.3%)	1
Infection	1/19 (5.3%)	1
Sepsis	1/19 (5.3%)	1
Investigations
Alkaline phosphatase increased	2/19 (10.5%)	2
Aspartate aminotransferase increased	2/19 (10.5%)	2
Bilirubin increased	3/19 (15.8%)	3
Gamma-glutamyltransferase increased	1/19 (5.3%)	1
Metabolism and nutrition disorders
Anorexia	2/19 (10.5%)	2
Dehydration	1/19 (5.3%)	1
Serum sodium decreased	2/19 (10.5%)	2
Renal and urinary disorders
Cystitis	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/19 (5.3%)	1
Dyspnea	2/19 (10.5%)	3
Hypoxia	1/19 (5.3%)	1
Pleural effusion	1/19 (5.3%)	1
Pneumonitis	1/19 (5.3%)	1
Respiratory disorder	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)
Blood and lymphatic system disorders
Hemoglobin decreased	12/19 (63.2%)	16
Gastrointestinal disorders
Abdominal pain	2/19 (10.5%)	2
Diarrhea	4/19 (21.1%)	5
Dry mouth	1/19 (5.3%)	1
Duodenal ulcer	1/19 (5.3%)	1
Flatulence	1/19 (5.3%)	1
Nausea	8/19 (42.1%)	10
Vomiting	3/19 (15.8%)	3
General disorders
Chills	2/19 (10.5%)	2
Fatigue	9/19 (47.4%)	13
Fever	3/19 (15.8%)	3
Hepatobiliary disorders
Hepatic failure	2/19 (10.5%)	2
Investigations
Activated partial thromboplastin time prolonged	1/19 (5.3%)	1
Alanine aminotransferase increased	3/19 (15.8%)	3
Alkaline phosphatase increased	1/19 (5.3%)	1
Aspartate aminotransferase increased	3/19 (15.8%)	3
Bilirubin increased	3/19 (15.8%)	3
Creatinine increased	4/19 (21.1%)	4
INR increased	1/19 (5.3%)	1
Leukocyte count decreased	2/19 (10.5%)	2
Lymphocyte count decreased	1/19 (5.3%)	1
Platelet count decreased	3/19 (15.8%)	3
Metabolism and nutrition disorders
Anorexia	2/19 (10.5%)	2
Blood glucose increased	2/19 (10.5%)	2
Dehydration	2/19 (10.5%)	2
Serum albumin decreased	2/19 (10.5%)	2
Serum calcium increased	1/19 (5.3%)	1
Serum potassium decreased	1/19 (5.3%)	2
Serum potassium increased	1/19 (5.3%)	1
Serum sodium decreased	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Myalgia	5/19 (26.3%)	6
Renal and urinary disorders
Protein urine positive	2/19 (10.5%)	2
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	2/19 (10.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.