Advanced CancerPhase 1NCT00551850
A Safety Study of an Oral EGFR Inhibitor, AV-412, Administered Three Times Weekly in Advanced Solid Tumor Patients
A Phase 1 study testing AV-412 in people with Advanced Cancer and Refractory Cancer, run by AVEO Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
The Epidermal Growth Factor Receptor (EGFR) is a validated target for the treatment of cancer, and agents targeting EGFR such as erlotinib (Tarceva®) are approved by the FDA for treatment of various solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Refractory Cancer
- What is being tested?
- AV-412
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2007to May 2010
- Phase
- Phase 1
- 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
- Ability to give written informed consent
- 18 years and older
- Evaluable disease or measurable disease according to RECIST.
- Subjects enrolled in the MTD Cohort B must have the following:
- A diagnosis of non-small cell lung carcinoma (NSCLC)
- Received prior therapy with erlotinib or gefitinib for a minimum of 12 weeks
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- Demonstrated disease stabilization or an objective response during that prior treatment
- Evidence of disease progression and measurable disease, according to RECIST
- Histologically confirmed solid tumor malignancy that is locally advanced or metastatic
- Disease that is currently refractory to, or not amenable to, standard therapy and/or subjects who are unwilling to try standard chemotherapy
- Disease that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor
- Karnofsky performance status ≥ 70%
- Life expectancy ≥ 3 months, as judged by the investigator
- No childbearing potential; or use of a medically acceptable form of contraception during the study through the end of follow-up period
Who cannot join
- Pregnant or lactating women
- Primary CNS malignancy and/or active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy
- Hematologic malignancies (including leukemia of any form, lymphoma, and multiple myeloma)
- Active second malignancy or history of another malignancy within 2 years with the exception of:
- Treated, non-melanoma skin cancers
- Treated carcinoma in situ (CIS) of the breast or cervix
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- Controlled, superficial carcinoma of the bladder
- T1a or b prostate carcinoma comprising < 5% of resected tissue, with prostate specific antigen (PSA) within normal limits (WNL) since resection
- Any of the following hematologic abnormalities:
- Hemoglobin ≤ 9.0 g/dL
- ANC ≤ 1500 per mm3
- Platelet count ≤ 75,000 per mm3
- Any of the following serum chemistry abnormalities:
- Total bilirubin > 1.5 × the ULN
- AST or ALT ≥ 3 × ULN (≥ 5 × ULN if due to hepatic involvement by tumor)
- Serum albumin < 2.5 g/dL
- Creatinine ≥ 1.5 × ULN
- Significant cardiovascular disease or condition, including:
- Congestive heart failure requiring therapy
- Ventricular arrhythmia requiring therapy
- Severe conduction disturbance (including QTc interval prolongation > 0.47 sec [corrected], history of a severe arrhythmia, or history of a familial arrhythmia [eg, Wolff-Parkinson-White syndrome])
- Angina pectoris requiring therapy
- Left ventricular ejection fraction (LVEF) < 50% by MUGA or echocardiogram
- Uncontrolled hypertension (as determined by investigator)
- Myocardial infarction (MI) within 6 months prior to administration of first dose
- >Class I cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria
- Significant gastrointestinal abnormalities, including:
- Requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- Grade 2 diarrhea due to any etiology
- Ulcerative colitis or Crohn's disease
- Known history of significant ophthalmologic abnormalities, including:
- Severe dry eye syndrome
- Keratoconjunctivitis sicca
- Sjogren's syndrome
- Severe exposure keratopathy
- Disorders that might increase the risk for epithelium-related complications (eg, bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis)
- Serious/active infection or any infection requiring parenteral antibiotics
- Inadequate recovery from prior antineoplastic therapy
- Inadequate recovery from any prior surgical procedure or major surgical procedure within 2 weeks prior to administration of first dose
- Life-threatening illness, or organ system dysfunction which, in the opinion of the investigator, would limit life expectancy to < 3 months, compromise the subject's safety, or interfere with evaluation of the safety of the study drug
- Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures
- Inability to comply with the protocol requirements
- Drugs and Treatments to be Excluded:
- Any prior therapy with the following:
- Doxorubicin at a cumulative dose > 450 mg/m2 or equivalent dose of another anthracycline (eg, daunorubicin, epirubicin, idarubicin) or anthracenedione (eg, mitoxantrone).
- HKI-272 or any other irreversible EGFR tyrosine kinase inhibitor (eg, CI- 1033 and similar agents).
- Therapy within 2 weeks prior to administration of the first dose or at any time during the study with:
- Herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components)
- Therapy within 3 weeks prior to administration of the first dose or at any time during the study with:
- Erlotinib (Tarceva®) or gefitinib (Iressa®)
- Antibodies to EGFR (eg, cetuximab, panitumumab)
- Agents targeting HER2 (ErbB2) (eg, trastuzumab, lapatinib)
- Therapy within 4 weeks prior to administration of the first dose or at any time during the study with:
- Chemotherapy with the exception of the following:
- Mitomycin C or nitrosoureas within 6 weeks prior to administration of first dose
- High-dose chemotherapy with stem cell support within 6 months prior to administration of first dose
- Other antineoplastic agents (standard or therapeutic) for primary malignancy, including but not limited to signal transduction inhibitors and monoclonal antibodies.
- Immunotherapy, cancer vaccines, biological response modifiers
- Systemic hormonal therapy within 4 weeks prior to administration of the first dose or at any time during the study, with the exception of the following allowed therapies:
- Hormonal therapy for appetite stimulation or contraception
- Nasal, ophthalmic, and topical glucocorticoid preparations
- Oral replacement therapy for adrenal insufficiency
- Stable hormonal therapy for prostate carcinoma
- Low-dose maintenance, or short course (ie, 7 days) steroid therapy for other conditions
- Any experimental therapy within 4 weeks prior to or at any time during the study
- Radiotherapy for the primary malignancy:
- Within 2 weeks prior to first study drug administration if involving ≤25% of marrow-containing bone
- Within 4 weeks prior to first study drug administration if involving >25% of marrow-containing bone
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Kansas Masonic Cancer Research Center
Kansas City, Kansas, 66160
Montefiore Medical Center
New York, New York, 10461
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase I, Multi-Center, Dose-Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of AV-412 Administered Orally Three Times Weekly to Subjects With Advanced Solid Tumors
The Epidermal Growth Factor Receptor (EGFR) is a validated target for the treatment of cancer, and agents targeting EGFR such as erlotinib (Tarceva®) are approved by the FDA for treatment of various solid tumors. AV-412 is a novel inhibitor of the EGFR-tyrosine kinase, with added activity against Her2 and other oncogenic kinases. Based on evidence of preclinical activity in various solid tumors, AV-412 is being developed as a possible novel treatment for cancer in humans.
PURPOSE: The purpose of this study is to test the safety and tolerability of AV-412, and determine the maximum tolerated dose of AV-412 when administered orally three times weekly.
Read the detailed description
This is an open-label, dose escalation trial, and all subjects will receive oral AV-412 administered three times weekly or once weekly for 4 weeks (1 cycle) to evaluate safety and tolerability of AV-412. Treatment duration will be a minimum of 2 consecutive dosing cycles (8 weeks), if tolerated.
- Upon completion of the 2 cycles, subjects with documented stable disease or an objective response may continue to receive therapy at the same dose and schedule previously utilized, as long as tolerability is acceptable, for up to 1 year. Treatment beyond 1 year from the time of enrollment will be reviewed on a case-by-case basis between the sponsor and investigator.
- Subjects experiencing unacceptable toxicities or with documented disease progression will be discontinued from further participation in the study Accrual to next cohort will occur only after acceptable tolerance has been demonstrated throughout Cycle 1, and only after consultation with medical monitor.
- Conditions
- Advanced Cancer, Refractory Cancer
- Being tested
- AV-412
- Keywords
- epidermal growth factor inhibitor, solid tumors, advanced cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AV-412Drug
oral solid dosage form administered three times weekly for 4 weeks (1 cycle)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: AV-412 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of AV-412 administered orally 3 times weekly and once weekly in subjects with relapsed or refractory solid tumor malignancies.
Measured: 4 weeks (1 cycle)
Secondary outcomes (3)
Characterize the pharmacokinetic (PK) profile of AV-412
Measured: 8 weeks ( 2 cycles)
Determine the effect of AV-412 on global and targeted gene expression patterns in blood from all subjects enrolled in the MTD expansion cohorts
Measured: 8 weeks (2 cycles)
Evaluate the antineoplastic activity of AV-412
Measured: 8 weeks (2 cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionOct 2009
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVEO Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pankaj Bhargava, M.D., Study director, AVEO Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00551850
- Sponsor's protocol ID
- AV-412-07-102
- Status last verified
- Sep 2011
- First submitted
- 30 Oct 2007
- Last updated
- 4 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multi-Center, Dose-Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of AV-412 Administered Orally Three Times Weekly to Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00551850
- Acronym / sponsor ID
- AV-412-07-102
- Conditions
- Advanced Cancer, Refractory Cancer
- Keywords
- epidermal growth factor inhibitor, solid tumors, advanced cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- AVEO Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 31 Oct 2007 (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.
The Epidermal Growth Factor Receptor (EGFR) is a validated target for the treatment of cancer, and agents targeting EGFR such as erlotinib (Tarceva®) are approved by the FDA for treatment of various solid tumors. AV-412 is a novel inhibitor of the EGFR-tyrosine kinase, with added activity against Her2 and other oncogenic kinases. Based on evidence of preclinical activity in various solid tumors, AV-412 is being developed as a possible novel treatment for cancer in humans.
PURPOSE: The purpose of this study is to test the safety and tolerability of AV-412, and determine the maximum tolerated dose of AV-412 when administered orally three times weekly.
Detailed description
This is an open-label, dose escalation trial, and all subjects will receive oral AV-412 administered three times weekly or once weekly for 4 weeks (1 cycle) to evaluate safety and tolerability of AV-412. Treatment duration will be a minimum of 2 consecutive dosing cycles (8 weeks), if tolerated.
- Upon completion of the 2 cycles, subjects with documented stable disease or an objective response may continue to receive therapy at the same dose and schedule previously utilized, as long as tolerability is acceptable, for up to 1 year. Treatment beyond 1 year from the time of enrollment will be reviewed on a case-by-case basis between the sponsor and investigator.
- Subjects experiencing unacceptable toxicities or with documented disease progression will be discontinued from further participation in the study Accrual to next cohort will occur only after acceptable tolerance has been demonstrated throughout Cycle 1, and only after consultation with medical monitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AV-412 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Ability to give written informed consent
- 18 years and older
- Evaluable disease or measurable disease according to RECIST.
- Subjects enrolled in the MTD Cohort B must have the following:
- Histologically confirmed solid tumor malignancy that is locally advanced or metastatic
Key exclusion criteria (70 listed)
- Pregnant or lactating women
- Primary CNS malignancy and/or active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy
- Hematologic malignancies (including leukemia of any form, lymphoma, and multiple myeloma)
- Active second malignancy or history of another malignancy within 2 years with the exception of:
- Any of the following hematologic abnormalities:
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 |
|---|---|---|
| AV-412oral solid dosage form administered three times weekly for 4 weeks (1 cycle) | Drug | 1 |
Primary outcome
Evaluate the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of AV-412 administered orally 3 times weekly and once weekly in subjects with relapsed or refractory solid tumor malignancies.
Time frame: 4 weeks (1 cycle)
3 secondary outcomes
Characterize the pharmacokinetic (PK) profile of AV-412
Time frame: 8 weeks ( 2 cycles)
Determine the effect of AV-412 on global and targeted gene expression patterns in blood from all subjects enrolled in the MTD expansion cohorts
Time frame: 8 weeks (2 cycles)
Evaluate the antineoplastic activity of AV-412
Time frame: 8 weeks (2 cycles)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2011.
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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.
Pankaj Bhargava, M.D. study director
AVEO Pharmaceuticals
4 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 AV-412 in people with Advanced Cancer and Refractory Cancer, run by AVEO Pharmaceuticals, Inc. at 4 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 14 inclusion and 70 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 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of AV-412 administered orally 3 times weekly and once weekly in subjects with relapsed or refractory solid tumor malignancies. (time frame: 4 weeks (1 cycle)). 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 4 Oct 2011.