PhII Study STA-9090 as Second or Third-Line Therapy for Metastatic Pancreas Cancer

Phase 2

Terminated

Conditions: Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer

Interventions: Drug: STA-9090
Radiation: Radiologic imaging
Procedure: blood draw

Registration Number: NCT01227018

Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary: RATIONALE: Heat shock protein (HSP)90 inhibitor STA-9090 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. PURPOSE: This phase II trial is studying how well hsp90 inhibitor STA-9090 works as second- or third-line therapy for the treatment of patients with metastatic pancreatic cancer.

Detailed Description: PRIMARY OBJECTIVES: I. To measure the 8-week disease control (CR + PR + SD) rate of therapy with STA-9090 in patients with metastatic pancreas cancer who have failed (either progressed or did not tolerate) one or two lines of prior therapy. SECONDARY OBJECTIVES: I. To determine response rate (by RECIST criteria v1.1). II. To determine overall survival. III. To evaluate the safety and toxicity profile in this patient population. TERTIARY OBJECTIVES: I. We will obtain from all patients blood samples pre and post therapy (after 1 week of therapy) and isolate serum for interrogation for a variety of biomarkers (eg AKT, Stat3, Caspase 3). OUTLINE: Patients receive Hsp90 inhibitor STA-9090 intravenous (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 weeks.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Microscopic confirmation of a diagnosis of metastatic adenocarcinoma (pathology may be from either the primary tumor or metastatic lesion) or poorly differentiated carcinoma of the pancreas s/p 1 or 2 prior chemotherapy regimens for metastatic disease (excluding neuroendocrine tumors, periampullary tumors and cystadenocarcinoma)
Patients who received adjuvant or neoadjuvant therapy will be eligible if they have progressed within 6 months of completing therapy and have not received a metastatic regimen or if they progressed > 6 months after completing therapy and have received 1-2 lines of therapy for metastatic disease
Measurable disease by RECIST criteria
ECOG PS 0 or 1
Life expectancy of at least 12 weeks
Absolute neutrophil count (ANC) >= 1,500/mm^3
Platelet count >= 100,000/mm^3
Creatinine =< 2.0 mg/dl
Total bilirubin =< 2.0 mg/dl
AST and ALT =< 2.5 x ULN in absence of liver metastasis; =< 5 x ULN in presence of liver metastasis
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of therapy
Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation
Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study-specific procedures

Exclusion Criteria

Primary brain tumors or active brain metastases; however, patients with a history of CNS metastases will be eligible if they have been treated and are stable for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for a minimum of 2 weeks prior to enrollment
History of stroke within 6 months of treatment or other significant neurological limitations
History of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty of coronary bypass surgery
History of or current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block
New York Heart Association class II/III/IV congestive heart failure with a history of dyspnea, orthopnea or edema that required current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics
Current or prior radiation therapy to the left hemithorax
Major surgery within 4 weeks prior to entering the study
Poor venous access for study drug administration or would require a peripheral or central indwelling catheter for study drug administration; study drug administration via indwelling catheters is prohibited at this time
Use of any investigational agents within 4 weeks prior to entering the study
History of severe allergic reactions to excipients (e.g., Polyethylene glycol 300 and Polysorbate 80), including severe hypersensitivity reactions defined as >= Grade 3 based on NCI CTCAE version 4.0
Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation or systemic steroids for treatment of autoimmune disease), however, patients may receive steroids for stable CNS metastases as described in exclusion criterion 1
Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
Ventricular ejection fraction (Ef) =< 55%
Baseline QTc > 470 msec or previous history of QT prolongation while taking other medications
Patients who received more than two lines of prior therapy for metastatic disease, neoadjuvant or post-op adjuvant therapy is not considered one line of therapy as long as there was > 6 months of disease-free interval
Pregnant or breast-feeding females

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
STA-9090	Radiologic imaging	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
STA-9090	STA-9090	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
STA-9090	blood draw	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Disease Control Rate	at 8 weeks from the start of therapy	Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions, and progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions. Disease control is defined as CR + PR + SD after 8 weeks of therapy.

Secondary Outcome Measures

Name	Time	Method
Best Response	On-treatment date, to date of disease progression (assessed up to 1 year)	Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Overall Survival	study entry to date of death or last date known alive (assessed over 2.5 yrs)	Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)
Number of Patients With Each Worst Grade Toxicity	On study date to 30 days following final dose of study drug	Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death