Study of AUY922 in Metastatic Pancreatic Cancer Who Are Resistant to First Line Chemotherapy

NCT01484860 | Terminated Phase 2 DMC

• 1 other identifier: DDP-922
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study to see how useful study drug AUY922 is in patients with metastatic pancreatic cancer who have received or are intolerant to first-line chemotherapy. AUY922 is an intravenous drug that blocks a protein called heat shock protein 90 (Hsp90). Hsp90 works by keeping a number of other proteins stable and active, including many proteins that are involved in tumor growth and death. When Hsp90 is blocked from working, it is believed that many of the other proteins that it stabilizes will also be blocked, which will cause tumor growth to slow or stop. During the study, patients will visit the clinic once a week, every 4 week cycles to receive AUY922 intravenously and to have tests and procedures done. As part of the study, archived tumor tissue will be collected and patients will be asked to have blood samples taken for pharmacokinetic testing. Patients will be invited to take part in an optional banking of blood samples for future studies. The primary hypothesis of this study is that AUY922 improves disease control rate compared with what would be expected from best supportive care.

Conditions

Adenocarcinoma of the Pancreas; Metastatic Disease

Keywords

AUY922; Pancreas; Pancreatic cancer; Adenocarcinoma of the pancreas; Cancer of the pancreas; Metastatic; Advanced; Advanced disease; Prior systemic anticancer therapy

Outcome Measures

Primary Outcomes (1)

• Determine anti-tumor activity using disease control rate

  Disease control rate is defined as objective response rate plus prolonged stable disease (≥16 weeks).

  18-20 months

Secondary Outcomes (4)

• Determine safety and tolerability of AUY922

  18-20 months

• Progression Free Survival

  18-20 months

• Overall Survival

  18-20 months

• Stable Disease Duration

  18-20 months

Study Arms (1)

AUY922

EXPERIMENTAL

AUY922 will be administered as a weekly infusion at a dose of 70 mg/m2 based on the recommended phase II dose from the phase I study or alternate dose based on the phase I study final results.The drug will be continued until disease progression or unacceptable toxicity. One cycle will be defined as 4 weeks of treatment.

Drug: AUY922

Interventions

AUY922 DRUG

AUY922 is a solution for intravenous administration Dose: 70 mg/m2 over 1 hour, weekly

AUY922

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas with metastatic disease
• Patients have received at least one prior systemic anticancer therapy for their advanced disease, which may include a gemcitabine based or 5-FU based therapeutic regimen. Patients with resected disease who relapse within 6 months of completion of adjuvant gemcitabine would also be eligible.
• Patients with progressive disease (radiological confirmation required) after at least one line of chemotherapy for pancreatic adenocarcinoma. Patients must have at least one measurable lesion as defined by RECIST criteria. Irradiated lesions are only evaluable for disease progression.
• Patient's age is ≥ 18 years of age
• Patients may have received prior radiation treatment for management of local disease providing that disease progression has been documented, all toxicities have resolved, to ≤ grade 1 and the last fraction of radiation treatment was completed at least 4 weeks prior to randomization (2 weeks for palliative radiotherapy).
• ECOG performance status of 0 or 1.
• Life expectancy of greater than 12 weeks
• Patients must have following laboratory values within 7 days prior to starting treatment:
• Hematological:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 90 g/L
• Platelets (plt) ≥ 100 x 109/L
• Biochemistry:
• Potassium within normal limits
• Total calcium (corrected for serum albumin) and Phosphorus within normal limits

You may not qualify if:

• Patients with a history of another primary malignancy that is clinically significant or requires active intervention
• Prior treatment with any HSP90 or HDAC inhibitor compounds, including valproic acid
• Patients with a significant history of cardiac disease, including:
• Impaired cardiac function, including any one of the following:
• History (or family history) of long QT syndrome
• Mean QTc ≥ 450 msec on baseline ECG
• History of clinically manifested ischemic heart disease ≤ 6 months prior to study start
• History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO
• Clinically significant ECG abnormalities
• History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes
• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Clinically significant resting bradycardia (\< 50 beats per minute)
• Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing start of treatment.
• Obligate use of a cardiac pacemaker
• Patients with a serious active infection at the time of registration or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Malcolm J. Moore, M.D.

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: December 2, 2011
• Study Start: January 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

CA (1)