MelanomaPhase 2NCT01174238

A Two Arm Trial of Axitinib and Carboplatin/Paclitaxel in Melanoma

A Phase 2 study testing Axitinib, Carboplatin and Paclitaxel in people with Melanoma, run by Adil Daud at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Melanoma
What is being tested?: Axitinib, Carboplatin and Paclitaxel
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteUnited States
Study dates: Jul 2010to Dec 2013
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 or cytologically proven melanoma with Stage IV or unresectable stage III disease.
Male or female, age ≥ 18 years.
Resolution of all acute toxic effects of prior radiotherapy, chemotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
May have ≤ 2 prior chemotherapy treatments and any prior immunotherapy treatments. These can include dacarbazine and/or temozolomide but not carboplatin or paclitaxel.
At least 2 weeks since the end of prior systemic treatment (4 weeks for bevacizumab-containing regimens), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤ 1 or back to baseline except for alopecia or hypothyroidism.
No evidence of preexisting uncontrolled hypertension. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.

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Adequate organ function as defined by the following criteria:
Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
Total serum bilirubin ≤ 1.5 x ULN (Grade 0-1)
Absolute neutrophil count (ANC) ≥ 1500 /ml
Platelets ≥ 100,000/mL
Hemoglobin ≥ 9.0 g/dL (may be transfused or erythropoietin treated)
Serum calcium ≥12.0 mg/dL
Serum creatinine ≤ 1.5 x ULN
Patients with CNS (central nervous system) metastasis must have had either:
Resected CNS metastasis without evidence of recurrence for > 12 weeks, OR
Brain metastasis treated by stereotactic radiosurgery without evidence of recurrence or progression for 12 weeks, OR
Multiple brain lesions treated with whole brain radiation therapy with stable disease off corticosteroids for at least 12 weeks prior to the start of therapy, AND
Without any evidence of leptomeningeal disease, AND
Patients must be neurologically intact.
May have previous adjuvant therapy with interferon, vaccines, or therapy with IL-2 or GM-CSF.
Measurable disease by RECIST criteria.
ECOG performance status 0 or 1.

Who cannot join

Major surgery within 4 weeks of starting the study treatment.
Radiation therapy within 2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
NCI CTCAE version 4.0 grade 2 or greater hemorrhage within 4 weeks of starting study treatment.
History of hemoptysis or bleeding from GI tract.
History of abdominal fistulae or perforation within 6 months prior to starting study treatment.
History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease on screening CT or MRI scan.

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Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
Hypertension that cannot be controlled by medications.
Current use or anticipated need for treatment with drugs that are known potent CYP3A inhibitors (grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
Current use or anticipated need for treatment with drugs that are known potent CYP3A or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
CNS disease on stable dexamethasone
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Cutaneous Onocology Group at the Helen Dillar Family Comprehensive Cancer Center UCSF
San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Two Arm Phase II Trial of Sequential Axitinib and Carboplatin/Paclitaxel in Melanoma With Correlative FLT PET Scans (3'Deoxy-3'-18F-Fluorothymidine Positron Emission Tomography Scans)(CC# 10852)

This is a two arm prospective Phase II pilot trial designed to determine the optimal duration of break between axitinib and chemotherapy with carboplatin/paclitaxel in melanoma. In this study, 6 patients will be enrolled to Arm A, the FLT PET scan (3'deoxy-3'-18F-Fluorothymidine positron emission tomography scans)cohort. 30 patients will be enrolled to Arm B, the treatment-only cohort. 36 total patients will be enrolled. The treatment schedule will be the same in either cohort, with the exception of the FLT PET scans.

Read the detailed description

This is a two arm prospective Phase II pilot trial designed to determine the optimal duration of break between axitinib and chemotherapy with carboplatin/paclitaxel in melanoma. In this study, 6 patients will be enrolled to Arm A, the FLT-PET (3'deoxy-3'-18F-Fluorothymidine positron emission tomography scans)cohort. 30 patients will be enrolled to Arm B, the treatment-only cohort. 36 total patients will be enrolled. The treatment schedule and dose will be the same in either cohort, with the exception of the FLT PET scans. We are enrolling only 6 patients to Arm A, the FLT-PET cohort, because of study financial considerations.

Patients will be enrolled in Arm A first, the FLT-PET cohort, to accommodate the radiological manufacture of the FLT-PET scan dye. It is expensive to manufacture and it is not usable forever. However if a patient is unable to participate in Arm A because of logistical issues, i.e. not being able to travel to UCSF for FLT-PET scans we will offer them participation in Arm B so that they can receive treatment that is not available off study.

Each treatment cycle will last for 21days. During Cycle 1, patients will be treated with:

Days 1-14: axitinib 5 mg PO twice daily Days 15-21: break from treatment

In all cycles after Cycle 1, patients will be treated with:

Day 1: paclitaxel 175 mg/m2 over 3 hours followed by carboplatin AUC 5 (AUC 5 is a term used to describe the dosing of carboplatin based on a patient's height, weight and kidney function) over 45 minutes Days 1-14: axitinib 5 mg PO twice daily Days 15-21: break from treatment Arm A: FLT PET cohort subjects will have FLT PET scans up to 2 weeks prior to day 1 and on days 14, 17, and 21 of cycle 1.

Arm B: Treatment-only patients will receive administration of axitinib and carboplatin/paclitaxel on the same schedule and dose as Arm A but will not have FLT PET scans. Patients in Arm B will have standard tumor assessment with FDG PET-CT scans (F18-deoxyglucose positron emission tomography scans), CT Scans, and MRI's.

Conditions: Melanoma
Being tested: Axitinib, Carboplatin, Paclitaxel
Keywords: Melanoma, Axitinib, Carboplatin, Paclitaxel
Medical subject headings: Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AxitinibDrug
5mg BID Axitinib Days 1-14 for dual therapy - 5mg BID QD for patients on monotherapy
CarboplatinDrug
Day 1 of each 21 day cycle in combination with paclitaxel if patients are in dual therapy phase
PaclitaxelDrug
Day 1 of each 21 Day cycle in combination with Carboplatin if patients on on dual therapy phase.

Study groups in NCT01174238
Study group	Role	What they receive
Arm A	Experimental	Patients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. In addition patients enrolled in Arm A will also have FLT-PET scans. Receives: Drug: Axitinib; Drug: Carboplatin; Drug: Paclitaxel
Arm B	Experimental	Patients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. Patients enrolled in Arm B will not have FLT-PET scans. Receives: Drug: Axitinib; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR)
ORR is defined as the percentage of patients with tumor size reduction, i.e. the sum of partial responses plus complete responses. Radiographic response was evaluated using RECIST criteria during every 21-day cycle of treatment.
Measured: Monthly during study treatment, up to 12 months

Secondary outcomes (4)

Optimal Interval Between the End of Axitinib Therapy and Initiation of Chemotherapy
Optimal interval between the end of axitinib therapy and initiation of chemotherapy, as determined using FLT PET as a Radiological Biomarker information of Resumption of DNA Synthesis Following Axitinib Therapy.
Measured: Days 1, 14, 17, and 20 of cycle 1
Overall Survival (OS)
Overall survival is the duration from first dose of study medication to death. For participants who are alive, overall survival is censored at the last contact.
Measured: Baseline until death or up to 24 months
Time to Progression (TTP)
Measured: within 7 days of odd cycles after cycle 1 for the duration of treatment, up to 12 cycles
Increase From Nadir in the Sum of Maximum (18)F-FLT Uptake Values After Treatment Holiday
(18)F-FLT uptake values following a 7-day treatment holiday compared to the lower of Baseline or Day 14 value.
Measured: Baseline, Day 14, Day 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2010Dec 2013

First posted3 Aug 2010 (estimated)
Study startJul 2010
Primary completionAug 2013
Study completionDec 2013

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.
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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01174238
Sponsor's protocol ID: 10852
Status last verified: May 2018
First submitted: 28 Jul 2010
Last updated: 8 Jun 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two Arm Phase II Trial of Sequential Axitinib and Carboplatin/Paclitaxel in Melanoma With Correlative FLT PET Scans (3'Deoxy-3'-18F-Fluorothymidine Positron Emission Tomography Scans)(CC# 10852)
ClinicalTrials.gov ID: NCT01174238
Acronym / sponsor ID: 10852
Conditions: Melanoma
Keywords: Melanoma, Axitinib, Carboplatin, Paclitaxel
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Adil DaudUniversity, hospital or other
Study start: Jul 2010
Primary completion: Aug 2013 (actual)
Study completion: Dec 2013 (actual)
First posted: 3 Aug 2010 (estimated)
Results: Posted 8 Jun 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This is a two arm prospective Phase II pilot trial designed to determine the optimal duration of break between axitinib and chemotherapy with carboplatin/paclitaxel in melanoma. In this study, 6 patients will be enrolled to Arm A, the FLT-PET (3'deoxy-3'-18F-Fluorothymidine positron emission tomography scans)cohort. 30 patients will be enrolled to Arm B, the treatment-only cohort. 36 total patients will be enrolled. The treatment schedule and dose will be the same in either cohort, with the exception of the FLT PET scans. We are enrolling only 6 patients to Arm A, the FLT-PET cohort, because of study financial considerations.

Each treatment cycle will last for 21days. During Cycle 1, patients will be treated with:

Days 1-14: axitinib 5 mg PO twice daily Days 15-21: break from treatment

In all cycles after Cycle 1, patients will be treated with:

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm A	Experimental	Drug: Axitinib, Drug: Carboplatin, Drug: PaclitaxelPatients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. In addition patients enrolled in Arm A will also have FLT-PET scans.
Arm B	Experimental	Drug: Axitinib, Drug: Carboplatin, Drug: PaclitaxelPatients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. Patients enrolled in Arm B will not have FLT-PET scans.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

Histologically or cytologically proven melanoma with Stage IV or unresectable stage III disease.
Male or female, age ≥ 18 years.
Resolution of all acute toxic effects of prior radiotherapy, chemotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
May have ≤ 2 prior chemotherapy treatments and any prior immunotherapy treatments. These can include dacarbazine and/or temozolomide but not carboplatin or paclitaxel.
At least 2 weeks since the end of prior systemic treatment (4 weeks for bevacizumab-containing regimens), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤ 1 or back to baseline except for alopecia or hypothyroidism.

Key exclusion criteria (16 listed)

Major surgery within 4 weeks of starting the study treatment.
Radiation therapy within 2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
NCI CTCAE version 4.0 grade 2 or greater hemorrhage within 4 weeks of starting study treatment.
History of hemoptysis or bleeding from GI tract.
History of abdominal fistulae or perforation within 6 months prior to starting study treatment.

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
Axitinib5mg BID Axitinib Days 1-14 for dual therapy - 5mg BID QD for patients on monotherapy	Drug	Arm A, Arm B
CarboplatinDay 1 of each 21 day cycle in combination with paclitaxel if patients are in dual therapy phase	Drug	Arm A, Arm B
PaclitaxelDay 1 of each 21 Day cycle in combination with Carboplatin if patients on on dual therapy phase.	Drug	Arm A, Arm B

Primary outcome

Objective Response Rate (ORR)
Time frame: Monthly during study treatment, up to 12 months
ORR is defined as the percentage of patients with tumor size reduction, i.e. the sum of partial responses plus complete responses. Radiographic response was evaluated using RECIST criteria during every 21-day cycle of treatment.

4 secondary outcomes

Optimal Interval Between the End of Axitinib Therapy and Initiation of Chemotherapy
Time frame: Days 1, 14, 17, and 20 of cycle 1
Overall Survival (OS)
Time frame: Baseline until death or up to 24 months
Time to Progression (TTP)
Time frame: within 7 days of odd cycles after cycle 1 for the duration of treatment, up to 12 cycles
Increase From Nadir in the Sum of Maximum (18)F-FLT Uptake Values After Treatment Holiday
Time frame: Baseline, Day 14, Day 20

Results and safety

Results posted to the registry on 8 Jun 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Axitinib + Carboplatin/Paclitaxel	38	36

Primary outcome: Objective Response Rate (ORR)

Time frame: Monthly during study treatment, up to 12 months. Number. Unit: percentage of patients

Measure	Axitinib + Carboplatin/Paclitaxel n = 36
Value	22

Population analysed: Two patients discontinued treatment due to toxicity within the first 3 weeks, prior to the first infusion of paclitaxel/carboplatin, and were considered to be evaluable for toxicity but not for response.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Patients were assessed during study treatment for adverse events up to 12 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Axitinib + Carboplatin/Paclitaxel	12 of 32 (37.5%)	32 of 32 (100%)	0 of 32
Axitinib + Carboplatin/Paclitaxel and With FLT-PET Scans	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Melanoma

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
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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.

Adil Daud, MD principal investigator

Cutaneous Oncology Group at the Helen Dillar Family Comprehensive Cancer Center at UCSF

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 Axitinib, Carboplatin and Paclitaxel in people with Melanoma, run by Adil Daud 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 23 inclusion and 16 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 Jun 2018. 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 8 Jun 2018). 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?

Objective Response Rate (ORR) (time frame: Monthly during study treatment, up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01174238.

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 Jun 2018.