Metastatic or Unresectable Solid Tumor MalignancyPhase 1NCT01226732
A Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
A Phase 1 study testing Capecitabine and Hsp90 Inhibitor AUY 922 in people with Metastatic or Unresectable Solid Tumor Malignancy, run by SCRI Development Innovations, LLC at 3 sites in United States.
Trial summary
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic or Unresectable Solid Tumor Malignancy
- What is being tested?
- Capecitabine and Hsp90 Inhibitor AUY 922
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2010to Jun 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate.
- Patient must be ≥4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy or chemotherapy). Patients who received a small molecule targeted therapy as part of their first line treatment regimen must be ≥4 weeks or ≥5 half lives from administration of last dose whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
- Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A).
- Life expectancy of ≥3 months.
- At least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (see Section 9).
- Normal bone marrow function defined as:
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- Absolute neutrophil count (ANC) ≥1500/μL
- Hemoglobin (Hgb) ≥9 g/dL
- Platelets ≥100,000/μL
- Adequate hepatic function defined as:
- AST or ALT and alkaline phosphatase (ALP) must be ≤3 x ULN, or ≤5 x ULN in patients with liver metastases
- Total bilirubin ≤1.5 x the institutional ULN
- Renal function defined as:
- Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance ≥40 mL/min
- Normal electrolytes defined as:
- Phosphorous ≥ LLN
- Magnesium ≥ LLN
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment and during the 6 months following completion of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
- Must be ≥18 years of age.
- Patients must be accessible for treatment and follow-up.
- Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
Who cannot join
- Untreated CNS metastases. Patients with treated CNS metastases may be enrolled, provided the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
- Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
- Impaired cardiac function with 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 (i.e. myocardial infarction and/or unstable angina) ≤6 months prior to study start
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- History of heart failure or left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO
- Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block.
- 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 QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922 (see Appendix D).
- Obligate use of a cardiac pacemaker
- Impairment of gastrointestinal function or gastrointestinal disease that in the opinion of the Investigator may significantly alter the absorption of study drugs (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).
- Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
- Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant (positive pregnancy test) or lactating.
- Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up procedures.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Florida Cancer Specialists
Fort Myers, Florida, 33916
Tennessee Oncology
Nashville, Tennessee, 37203
Oklahoma University
Oklahoma City, Oklahoma, 71304
About this study
Official title: A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including colorectal and breast cancer.
- Being tested
- Capecitabine, Hsp90 Inhibitor AUY 922
- Keywords
- Solid tumor, Capecitabine, Hsp90 inhibitor AUY922
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Taken orally twice daily on Days 1 through 14 of 21 day cycle.
Hsp90 Inhibitor AUY 922Drug
IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Hsp90 Inhibitor AUY922: 22mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
| Dose Level 2 | Experimental | Hsp90 Inhibitor AUY922: 28mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
| Dose Level 3 | Experimental | Hsp90 Inhibitor AUY922: 40mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
| Dose Level 4 | Experimental | Hsp90 Inhibitor AUY922: 55mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
| Dose Level 5 | Experimental | Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
| Dose Level 6 | Experimental | Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1250mg/m2 PO BID d 1-14 of 21-day cycles Receives: Drug: Capecitabine; Drug: Hsp90 Inhibitor AUY 922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Determination
To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.
Measured: 18 months
Secondary outcomes (2)
Drug Related Toxicities
To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen.
Measured: 18 months
Preliminary Efficacy Assessment: Response Rate (RR)
Response Rate (RR) is defined as the total number of patients with Complete Response (CR) or Partial Response (PR) as defined in RECIST v2. CR is defined as the dissappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor markers. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionJul 2013
- Study completionJun 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.
- Other trials for Metastatic or Unresectable Solid Tumor MalignancyStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Johanna C Bendell, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01226732
- Sponsor's protocol ID
- SCRI GI 143
- Status last verified
- Feb 2022
- First submitted
- 18 Oct 2010
- Last updated
- 8 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01226732
- Acronym / sponsor ID
- SCRI GI 143
- Keywords
- Solid tumor, Capecitabine, Hsp90 inhibitor AUY922
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Nov 2010
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 22 Oct 2010 (estimated)
- Results
- Posted 14 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including colorectal and breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 22mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles |
| Dose Level 2 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 28mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles |
| Dose Level 3 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 40mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles |
| Dose Level 4 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 55mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles |
| Dose Level 5 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles |
| Dose Level 6 | Experimental | Drug: Capecitabine, Drug: Hsp90 Inhibitor AUY 922Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1250mg/m2 PO BID d 1-14 of 21-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate.
- Patient must be ≥4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy or chemotherapy). Patients who received a small molecule targeted therapy as part of their first line treatment regimen must be ≥4 weeks or ≥5 half lives from administration of last dose whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.
- Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A).
- Life expectancy of ≥3 months.
- At least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (see Section 9).
Key exclusion criteria (18 listed)
- Untreated CNS metastases. Patients with treated CNS metastases may be enrolled, provided the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
- Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
- Impaired cardiac function with any one of the following:
- Impairment of gastrointestinal function or gastrointestinal disease that in the opinion of the Investigator may significantly alter the absorption of study drugs (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).
- Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
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 |
|---|---|---|
| CapecitabineAlso: XelodaTaken orally twice daily on Days 1 through 14 of 21 day cycle. | Drug | Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Dose Level 5, Dose Level 6 |
| Hsp90 Inhibitor AUY 922IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle | Drug | Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Dose Level 5, Dose Level 6 |
Primary outcome
Dose Determination
Time frame: 18 months
To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors.
2 secondary outcomes
Drug Related Toxicities
Time frame: 18 months
Preliminary Efficacy Assessment: Response Rate (RR)
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Johanna C Bendell, MD study chair
SCRI Development Innovations, LLC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Capecitabine and Hsp90 Inhibitor AUY 922 in people with Metastatic or Unresectable Solid Tumor Malignancy, run by SCRI Development Innovations, LLC at 3 sites in United States.
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 21 inclusion and 18 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 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 14 Jan 2015). 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?
Dose Determination (time frame: 18 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 8 Mar 2022.