Adenocarcinoma of the PancreasPhase 2NCT01484860
Study of AUY922 in Metastatic Pancreatic Cancer Who Are Resistant to First Line Chemotherapy
A Phase 2 study testing AUY922 in people with Adenocarcinoma of the Pancreas and Metastatic Disease, run by University Health Network, Toronto at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Pancreas, Metastatic Disease
- What is being tested?
- AUY922
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2012to Aug 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 22Show fewer
- 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
- Magnesium above LLN or correctable with supplements
- Adequate liver function defined as:
- AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN)
- AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if liver metastases are present
- Serum bilirubin ≤ 1.5 x ULN
- eGFR ≥ 50 mL /min
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization. Postmenopausal women must have been amenorrheic for ≥ 24 months in order to be considered "of non-childbearing potential". This should be documented appropriately in the patient's medical history.
Who cannot join
- 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
Show all 33Show fewer
- 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.
- Patients with a known central nervous system metastases. CT scan of the brain is NOT required unless there is suspicion of CNS metastases.
- Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
- Pregnant or lactating females.
- Women of child bearing potential or sexually active males who are not employing adequate contraception. Adequate methods of contraception include use of oral contraceptives or Depot-Provera, with an additional barrier method (diaphragm with spermicidal gel OR condoms with spermicide); a double-barrier method (diaphragm with spermicidal gel AND condoms with spermicide); partner vasectomy and total abstinence.
- Patients who received systemic anti-cancer treatment prior to the first dose of study medication within the following time frames:
- Radiotherapy, conventional chemotherapy: within 4 weeks
- Palliative radiotherapy: within 2 weeks
- Monoclonal antibodies: within 4 weeks
- Nitrosoureas and mitomycin: within 6 weeks
- Targeted agents or investigational dugs: within 4 weeks
- Patients who have had any surgery within 2 weeks prior to registration or who have not recovered from such therapy.
- Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection.
- Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted)
- Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)
- Unresolved diarrhea ≥ CTCAE grade 2 within 72 hours prior to registration
- Patients with acute or chronic renal disease. Chronic renal disease will be defined as patients who have stable creatinine ≥ to 1.5 ULN and/or eGFR ≤ 50mL/min. Acute renal disease will be defined as patients that have an acute (within less then 4 weeks) rise in creatinine to ≥ 1.5 ULN and/or eGFR ≤ 50mL/min, that has not resolved to the previously normal baseline levels.
- Patients with active liver disease that requires intervention.
- Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients). Patients competent but physically unable to sign the consent form may have the document signed by their nearest relative or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Single Arm Study of AUY922 in Patients With Metastatic Pancreatic Adenocarcinoma Who Are Resistant to First Line Chemotherapy
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.
Read more
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.
Read the detailed description
This is a single arm open label Phase II clinical trial evaluating the efficacy of AUY922 in patients with advanced pancreatic cancer who have been previously treated with or are intolerant to first line chemotherapy. The primary objective is to assess the efficacy of this agent by assessing the disease control rate (DCR) (objective response plus prolonged stable disease (>16 weeks).
The current standard therapy for patients who have advanced, metastatic or inoperable pancreatic cancer previously treated with or intolerant to first line chemotherapy is best supportive care. New treatment options are urgently needed.
Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone protein involved in the stabilization of a number of membrane and intracellular proteins including HER2, BCR-ABL, C-SRC, EGFR, RAF, VEGFR, AKT, and RAS. Many of these proteins are highly expressed in pancreatic adenocarcinoma.
AUY922 is a novel isoxazole-based HSP90 inhibitor. AUY922 acts by inhibiting HSP90 ATPase activity (IC50 of 30 nm) and preventing the formation of a multichaperone complex between HSP90 and other heat shock proteins. This then prevents HSP90 from performing its functions on client proteins.
- Conditions
- Adenocarcinoma of the Pancreas, Metastatic Disease
- Being tested
- AUY922
- Keywords
- AUY922, Pancreas, Pancreatic cancer, Adenocarcinoma of the pancreas, Cancer of the pancreas, Metastatic, Advanced, Advanced disease, Prior systemic anticancer therapy
- Medical subject headings
- Neoplasm Metastasis, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922Drug
AUY922 is a solution for intravenous administration Dose: 70 mg/m2 over 1 hour, weekly
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine anti-tumor activity using disease control rate
Disease control rate is defined as objective response rate plus prolonged stable disease (≥16 weeks).
Measured: 18-20 months
Secondary outcomes (4)
Determine safety and tolerability of AUY922
Number of participants with adverse events. Frequency, severity and grading of adverse events. Number of participants requiring dose reductions.
Measured: 18-20 months
Progression Free Survival
Determine antitumor activity of AUY922 using duration of time from start of treatment to time of progression or death (progression-free survival).
Measured: 18-20 months
Overall Survival
Determine antitumor activity of AUY922 using median time from date of enrollment to date of death (overall survival)
Measured: 18-20 months
Stable Disease Duration
Median time from date of enrollment to date of disease progression.
Measured: 18-20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma of the PancreasStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Malcolm J. Moore, M.D., Principal investigator, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01484860
- Sponsor's protocol ID
- DDP-922
- Status last verified
- Feb 2019
- First submitted
- 10 Nov 2011
- Last updated
- 15 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single Arm Study of AUY922 in Patients With Metastatic Pancreatic Adenocarcinoma Who Are Resistant to First Line Chemotherapy
- ClinicalTrials.gov ID
- NCT01484860
- Acronym / sponsor ID
- DDP-922
- Conditions
- Adenocarcinoma of the Pancreas, Metastatic Disease
- Keywords
- AUY922, Pancreas, Pancreatic cancer, Adenocarcinoma of the pancreas, Cancer of the pancreas, Metastatic, Advanced, Advanced disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Jan 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 2 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single arm open label Phase II clinical trial evaluating the efficacy of AUY922 in patients with advanced pancreatic cancer who have been previously treated with or are intolerant to first line chemotherapy. The primary objective is to assess the efficacy of this agent by assessing the disease control rate (DCR) (objective response plus prolonged stable disease (>16 weeks).
The current standard therapy for patients who have advanced, metastatic or inoperable pancreatic cancer previously treated with or intolerant to first line chemotherapy is best supportive care. New treatment options are urgently needed.
Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone protein involved in the stabilization of a number of membrane and intracellular proteins including HER2, BCR-ABL, C-SRC, EGFR, RAF, VEGFR, AKT, and RAS. Many of these proteins are highly expressed in pancreatic adenocarcinoma.
AUY922 is a novel isoxazole-based HSP90 inhibitor. AUY922 acts by inhibiting HSP90 ATPase activity (IC50 of 30 nm) and preventing the formation of a multichaperone complex between HSP90 and other heat shock proteins. This then prevents HSP90 from performing its functions on client proteins.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 | Experimental | Drug: AUY922AUY922 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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).
Key exclusion criteria (33 listed)
- 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:
- 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.
- Patients with a known central nervous system metastases. CT scan of the brain is NOT required unless there is suspicion of CNS metastases.
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 |
|---|---|---|
| AUY922AUY922 is a solution for intravenous administration Dose: 70 mg/m2 over 1 hour, weekly | Drug | AUY922 |
Primary outcome
Determine anti-tumor activity using disease control rate
Time frame: 18-20 months
Disease control rate is defined as objective response rate plus prolonged stable disease (≥16 weeks).
4 secondary outcomes
Determine safety and tolerability of AUY922
Time frame: 18-20 months
Progression Free Survival
Time frame: 18-20 months
Overall Survival
Time frame: 18-20 months
Stable Disease Duration
Time frame: 18-20 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
Related trials for Adenocarcinoma of the Pancreas
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 3
Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
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.
Malcolm J. Moore, M.D. principal investigator
Princess Margaret Hospital, Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AUY922 in people with Adenocarcinoma of the Pancreas and Metastatic Disease, run by University Health Network, Toronto at 1 site in Canada.
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 22 inclusion and 33 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: stopped early, as of the sponsor's last update on 15 Feb 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 Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
Determine anti-tumor activity using disease control rate (time frame: 18-20 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Feb 2019.