MelanomaPhase 2NCT01321437
Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma
A Phase 2 study testing therapeutic conventional surgery, laboratory biomarker analysis and Axitinib in people with Melanoma and Malignant Melanoma, run by University of California, Irvine at 1 site in United States.
Trial summary
The purpose of this research study is to determine the efficacy of Axitinib in treating individuals with Stage III melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Malignant Melanoma, Stage IIIA Melanoma
- What is being tested?
- therapeutic conventional surgery, laboratory biomarker analysis and Axitinib
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Dec 2016
- Phase
- Phase 2
- 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 documented melanoma with local lymph node stage III metastases.
- No prior systemic therapy. Prior adjuvant therapy with interferon does not count.
- No expectation of further effects of prior anticancer therapy.
- At least 1 target lesion, as defined by RECIST, that has not been irradiated. New lesions that have developed in a previously irradiated field may be used as sites of measurable disease assuming all other criteria are met. All target lesions must have a unidimensional diameter of at least 1 cm for spiral CT scans if the reconstruction algorithm is 0.5 cm), or an standard uptake value (SUV) value ≥ 2.5. Baseline measurements/evaluations must be completed within 4 weeks prior to treatment.
- Adequate bone marrow, hepatic, and renal function documented within 14 days prior to treatment as documented by:
- absolute neutrophil count (ANC, calculated as the absolute number of neutrophils and bands) ≥1.5 x 10^9 cells/L
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- platelets ≥100 x 10^9 cells /L
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN
- total bilirubin ≤1.5 x ULN
- serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min
- urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140, and the baseline diastolic blood pressure readings must be ≤90. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment.
- Written and voluntary informed consent
Who cannot join
- Stage IV disease
- History of hemoptysis
- Gastrointestinal abnormalities including:
- inability to take oral medication
- requirement for intravenous alimentation
- prior surgical procedures affecting absorption including gastric resection
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- treatment for active peptic ulcer disease in the past 6 months
- active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
- malabsorption syndromes.
- Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of epidermoid growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast growth factors (FGF) receptors.
- Current use or anticipated inability to avoid use of drugs that are known potent cytochrome P450 3A4 (CYP3A4) inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine).
- Current use or anticipated inability to avoid use of drugs that are known CYP3A4 or Cytochrome P450 1A2 (CYP1A2) inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's wort).
- Active seizure disorder or evidence of brain metastases. (Appropriate imaging should be done to rule out brain metastases.)
- A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
- History of a malignancy (other than melanoma) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years.
- 10. Major surgical procedure or any radiation therapy within 4 weeks of treatment, minimum rest period is 28 days post surgery; maximum rest period 56 days post surgery.
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence.
- Women who are pregnant or breast-feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chao Family Comprehensive Cancer Center
Orange, California, 92868
About this study
Official title: Phase 2 Study of the Anti-Angiogenesis Agent Axitinib (AG-013736) in Patients With Stage III Malignant Melanoma
The purpose of this research study is to determine the efficacy of Axitinib in treating individuals with Stage III melanoma.
Read the detailed description
The American Cancer Society estimates that there will be about 68,720 new cases of melanoma (29,900 in men and 25,200 in women) annually in the United States, and about 8,650 people will die from this cancer. The systemic therapy of advanced disease remains palliative until new agents are found that might improve the survival of patients with stage III melanoma.
Melanomas are often vascular, and a decrease in the number of blood vessels that supply the tumor may starve it of needed nutrients. An approach to blocking the growth of blood vessels that supply the tumor is to inhibit the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) signaling pathway. Axitinib (AG 013736) is a VEGFR TK inhibitor.
Because of the poor prognosis of patients with stage III melanoma and indications that anti-angiogenesis compounds might have clinically meaningful activity in this disease, a Phase 2 trial of the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) inhibitor Axitinib (AG 013736) is warranted.
- Conditions
- Melanoma, Malignant Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma
- Being tested
- therapeutic conventional surgery, laboratory biomarker analysis, Axitinib, pharmacological study
- Keywords
- Melanoma, Axitinib, Anti-angiogenesis, Neoadjuvant Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic conventional surgeryProcedure or surgery
Undergo surgery
laboratory biomarker analysisOther
Correlative studies
AxitinibDrug
Also called AG-013736, Inlyta
Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Axitinib | Experimental | Patients receive axitinib PO BID on days 1-28. Treatment repeats every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 14-21 days after completion of treatment. Beginning 28-56 days after surgery, patients receive axitinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity Receives: Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Drug: Axitinib; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate, Defined as the Percentage of Patients With a Confirmed Clinical Response (CR) or Partial Response (PR)
The response rate (CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) will be provided with an exact 95% 2-sided confidence interval calculated using a method based on the F distribution.
Measured: Up to 1 year
Secondary outcomes (4)
Progression-free Survival (PFS)
An estimate of the PFS curve from the Kaplan-Meier method will be presented. Median event time and a 2-sided 95% confidence interval for the median will be provided.
Measured: From the date of first dose of axitinib to the first date that criteria for progression were met or the patient died, assessed up to 1 year
Duration of Overall Response
Estimates of duration of overall response from the Kaplan-Meier method will be presented. Median event time (if appropriate) and a 2-sided 95% confidence interval for the median will be provided. The number of CR and PR patients may be small and thereby limit use of the Kaplan-Meier method to provide reliable information. In this case, descriptive statistics or listings will be provided.
Measured: From the day the criteria for PR or CR were met to the first day criteria for progression occurred, assessed up to 1 year
Survival
An estimate of the survival time curve from the Kaplan-Meier method will be presented. Median event time and a 2-sided 95% confidence interval for the median will be provided.
Measured: From the day of first dose of axitinib to the day of death, until at least one year after the initial dose for the last treated patient.
Frequencies of Patients Experiencing at Least One Adverse Event (AE)
Will be displayed by body system and preferred term according to Medical Dictionary for Regulatory Activities (MedDRA) terminology. Detailed information collected for each AE will include: description of the event, duration, whether the AE was serious, intensity, relationship to study drug, action taken, and clinical outcome. Intensity (severity) of the AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: Up to at least 28 days after the last dose of study drug, on average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2016
- Study completionDec 2016
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 MelanomaStudies of the same condition, open and under way.
- More trials run by University of California, IrvineThe 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, John P. Fruehauf, University of California, Irvine
- Investigators
- John P. Fruehauf, MD, PhD, Principal investigator, Chao Family Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01321437
- Sponsor's protocol ID
- UCI 10-55 [HS# 2011-8282]
- Other IDs
- 2011-8282, WS830279, NCI-2012-02173
- Status last verified
- Dec 2020
- First submitted
- 21 Mar 2011
- Last updated
- 20 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of the Anti-Angiogenesis Agent Axitinib (AG-013736) in Patients With Stage III Malignant Melanoma
- ClinicalTrials.gov ID
- NCT01321437
- Acronym / sponsor ID
- UCI 10-55 [HS# 2011-8282]
- Conditions
- Melanoma, Malignant Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma
- Keywords
- Melanoma, Axitinib, Anti-angiogenesis, Neoadjuvant Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Dec 2011
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 23 Mar 2011 (estimated)
- Results
- Posted 20 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine the efficacy of Axitinib in treating individuals with Stage III melanoma.
Detailed description
The American Cancer Society estimates that there will be about 68,720 new cases of melanoma (29,900 in men and 25,200 in women) annually in the United States, and about 8,650 people will die from this cancer. The systemic therapy of advanced disease remains palliative until new agents are found that might improve the survival of patients with stage III melanoma.
Melanomas are often vascular, and a decrease in the number of blood vessels that supply the tumor may starve it of needed nutrients. An approach to blocking the growth of blood vessels that supply the tumor is to inhibit the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) signaling pathway. Axitinib (AG 013736) is a VEGFR TK inhibitor.
Because of the poor prognosis of patients with stage III melanoma and indications that anti-angiogenesis compounds might have clinically meaningful activity in this disease, a Phase 2 trial of the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) inhibitor Axitinib (AG 013736) is warranted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib | Experimental | Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysis, Drug: Axitinib, Other: pharmacological studyPatients receive axitinib PO BID on days 1-28. Treatment repeats every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 14-21 days after completion of treatment. Beginning 28-56 days after surgery, patients receive axitinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically documented melanoma with local lymph node stage III metastases.
- No prior systemic therapy. Prior adjuvant therapy with interferon does not count.
- No expectation of further effects of prior anticancer therapy.
- At least 1 target lesion, as defined by RECIST, that has not been irradiated. New lesions that have developed in a previously irradiated field may be used as sites of measurable disease assuming all other criteria are met. All target lesions must have a unidimensional diameter of at least 1 cm for spiral CT scans if the reconstruction algorithm is 0.5 cm), or an standard uptake value (SUV) value ≥ 2.5. Baseline measurements/evaluations must be completed within 4 weeks prior to treatment.
- Adequate bone marrow, hepatic, and renal function documented within 14 days prior to treatment as documented by:
Key exclusion criteria (19 listed)
- Stage IV disease
- History of hemoptysis
- Gastrointestinal abnormalities including:
- Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of epidermoid growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast growth factors (FGF) receptors.
- Current use or anticipated inability to avoid use of drugs that are known potent cytochrome P450 3A4 (CYP3A4) inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine).
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 |
|---|---|---|
| therapeutic conventional surgeryUndergo surgery | Procedure or surgery | Axitinib |
| laboratory biomarker analysisCorrelative studies | Other | Axitinib |
| AxitinibAlso: AG-013736, InlytaAxitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events. | Drug | Axitinib |
| pharmacological studyCorrelative studies | Other | Axitinib |
Primary outcome
Overall Response Rate, Defined as the Percentage of Patients With a Confirmed Clinical Response (CR) or Partial Response (PR)
Time frame: Up to 1 year
The response rate (CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) will be provided with an exact 95% 2-sided confidence interval calculated using a method based on the F distribution.
4 secondary outcomes
Progression-free Survival (PFS)
Time frame: From the date of first dose of axitinib to the first date that criteria for progression were met or the patient died, assessed up to 1 year
Duration of Overall Response
Time frame: From the day the criteria for PR or CR were met to the first day criteria for progression occurred, assessed up to 1 year
Survival
Time frame: From the day of first dose of axitinib to the day of death, until at least one year after the initial dose for the last treated patient.
Frequencies of Patients Experiencing at Least One Adverse Event (AE)
Time frame: Up to at least 28 days after the last dose of study drug, on average of 1 year.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- 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.
John P. Fruehauf, MD, PhD principal investigator
Chao Family Comprehensive Cancer Center
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 therapeutic conventional surgery, laboratory biomarker analysis and Axitinib in people with Melanoma and Malignant Melanoma, run by University of California, Irvine at 1 site 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 16 inclusion and 19 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 20 Jan 2021. 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 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 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?
Yes. Results are posted in the registry (first posted 20 Jan 2021). 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?
Overall Response Rate, Defined as the Percentage of Patients With a Confirmed Clinical Response (CR) or Partial Response (PR) (time frame: Up to 1 year). 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 20 Jan 2021.