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Renal Cell CarcinomaPhase 2PrE0801NCT01649180

NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma

A Phase 2 study testing Axitinib in people with Renal Cell Carcinoma, run by PrECOG, LLC. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to see how well the study drug, axitinib, helps control renal (kidney) cancer that has come back (recurrent) or spread (metastatic). Patients must have already been treated as a participant in a clinical trial with sunitinib, sorafenib, pazopanib or placebo (sugar pill) after their initial… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Axitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesUnited States
Study dates
Jul 2012to Mar 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

  • Locally recurrent or metastatic RCC requiring systemic therapy following treatment (tx) with sorafenib, sunitinib, pazopanib, or placebo on an adjuvant study
  • Required to have primary or recurrence tumor samples containing clear cell variant RCC with <50% of any other histology
  • Recurrence must occur ≥ 3 months following end of exposure to the adjuvant intervention
  • Received ≥ 3 six week cycles of prior adjuvant tx with sorafenib, sunitinib, pazopanib or placebo in the adjuvant setting on a clinical trial, or recurrence >3 months of tx on an adjuvant placebo arm
  • Required to have measurable recurrent or metastatic disease that is not curable by standard radiation therapy or surgery
  • Male or female, ≥ 18 years old
Show all 33Show fewer
  • ECOG PS 0 or 1
  • Blood pressure (B/P) must be controlled at time of enrollment. Tx with antihypertensive medication(s) is allowed. Controlled B/P is defined as in clinic measurement of systolic B/P ≤ 140 mm Hg AND diastolic B/P ≤ 90 mm Hg. If B/P is uncontrolled at time of planned enrollment, tx or optimization with antihypertensive medication(s) may be initiated in order to control B/P. Patient may be considered for enrollment when this has happened.
  • Women must not be pregnant or breastfeeding
  • Men and women who are of reproductive potential must be willing to employ an effective method of birth control/contraception
  • Willingness and ability to comply with scheduled visits, tx plans, laboratory tests, and other study procedures
  • Ability to understand and willingness to sign an IRB-approved informed consent
  • Adequate organ function as evidenced by the following, obtained within 28 days prior to registration:
  • Absolute neutrophil count (ANC) ≥ 1250 cells/mm³
  • Platelet count ≥ 75,000 cells/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Total direct serum bilirubin ≤ 1.5x upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 x ULN unless there are liver metastases in which case AST and ALT ≤ 5.0 x ULN
  • Serum creatinine <1.5 x ULN or calculated creatinine clearance ≥ 45 mL/min
  • Urine protein <2+ by urine dipstick
  • Resolution of all previous tx-related toxicity to ≤ grade 1 or back to baseline
  • No major surgery <4 weeks or radiation therapy <2 weeks of starting study tx. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
  • No clinically significant gastrointestinal abnormalities
  • No current use or anticipated need for tx with drugs that are known potent CYP3A4 inhibitors
  • No current or anticipated need for tx with drugs that are known CYP3A4 or CYP1A2 inducers
  • No current requirement of anticoagulant therapy with oral vitamin K antagonists
  • No untreated brain metastases, spinal cord compression, or carcinomatous meningitis. Patients must be off oral (systemic) steroids prior to registration. Inhalational steroids, e.g., for asthma, emphysema are permissible.
  • No serious uncontrolled medical disorder or active infection that would impair their ability to receive study tx
  • None of the following conditions within the 6 months prior to study drug: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or pulmonary embolism
  • No known HIV or AIDS-related illness
  • No other active malignancy
  • No dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol
  • No other severe acute/chronic medical or psychiatric condition or lab 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 patient inappropriate for entry into this study

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Cleveland Clinic, Taussig Cancer Institute

    Cleveland, Ohio, 44195

  • Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition (TKI) at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (RCC)

The purpose of this study is to see how well the study drug, axitinib, helps control renal (kidney) cancer that has come back (recurrent) or spread (metastatic). Patients must have already been treated as a participant in a clinical trial with sunitinib, sorafenib, pazopanib or placebo (sugar pill) after their initial surgery.

This study will examine the effect of adjuvant tyrosine kinase inhibition (TKI) therapy (sorafenib, sunitinib or pazopanib) on subsequent exposure to TKI with axitinib in the first-line recurrent or metastatic setting.

Read the detailed description

Approximately 64,770 cases of cancer involving the kidney and renal pelvis were diagnosed in the United States in 2012 and 13,570 deaths occurred from these tumors. The rate of Renal Cell Carcinoma (RCC) has increased by 2% per year for the past 65 years. The reason for this increase in unknown but smoking and obesity are risk factors for the development of RCC. Early stage disease is typically treated with resection with definitive intent with partial or radical nephrectomy. Patients with metastatic disease are often treated with systemic therapy with palliative intent. Systemic therapeutic options include so-called targeted therapies, and less often chemotherapy and immunomodulatory therapies (interferon alpha and interleukin-2).

The Food and Drug Administration (FDA) has approved six targeted agents for the treatment of advanced and metastatic renal cell carcinoma that fall into two general classes - vascular endothelial growth factor (VEGF) inhibitors and inhibitors of mammalian target of rapamycin (mTOR). On the basis of several randomized phase III studies, vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor therapy has become the generally preferred treatment for recurrent and metastatic ccRCC (clear cell Renal Cell Carcinoma) in the first-line setting. Treatment of ccRCC with VEGF-inhibition in the first-line metastatic setting, is associated with a progression-free survival of approximately 11 months. Vascular endothelial growth factor (VEGF) inhibitor therapy in the second-line remains active, but to a lesser degree - progression-free survival (PFS) has been reported to be between 5 and 7 months.

Adjuvant treatment of high-risk, early-stage ccRCC with VEGFR2 TKI therapy following definitive resection has become an area of active investigation. The ASSURE trial (ECOG 2805) recently completed accrual, and other adjuvant trials - i.) SORCE (sorafenib for 3 or 1 year versus placebo), ii.) S-Trac (sunitinib versus placebo) - are in accrual.

Axitinib (AG-013736, Pfizer Inc.), a receptor-tyrosine kinase inhibitor that is selective for VEGFR1, 2, and 3, is an important new agent for use in metastatic RCC. Axitinib has been examined extensively in RCC, and it has been shown to be safe, well-tolerated, and highly active. On January 27, 2012, the FDA approved axitinib for the treatment of advanced RCC after failure of one prior systemic therapy.

Being tested
Axitinib
Keywords
RCC, Clear Cell Renal Cell Carcinoma, ccRCC, Metastatic RCC, Recurrent RCC, Kidney Cancer, Kidney Neoplasms, Axitinib, AG-013736, Tyrosine Kinase Inhibition, TKI
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

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

  • AxitinibDrug

    Also called AG-013736, Tyrosine Kinase Inhibitor (TKI)

    Axitinib 5 mg orally with food every 12 hours. One cycle=28 days.

Study groups in NCT01649180
Study groupRoleWhat they receive
AxitinibExperimentalAxitinib will be given orally and will continue until progression of disease.
Receives: Drug: Axitinib

What is being measured

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

  1. Progression-free Survival

    Progression-free survival is defined as the time from registration to disease progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Assessed every 12 weeks up to 36 months

Secondary outcomes (4)

  1. Overall Response Rate

    Best overall response was evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0). Response is defined as complete response or partial response.

    Complete Response (CR): disappearance of all target lesions Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions

    Measured: Assessed every 12 weeks up to 36 months

  2. Biospecimen Banking for IL-8 and VEGF-A

    To bank biospecimens for the retrospective determination of whether baseline or changes in cytokine levels of IL-8 and VEGF-A predict response to treatment in this setting. Banking of plasma and serum is optional but strongly encouraged.

    Note: The assays to assess cytokine levels of IL-8 and VEGF-A were not performed because the study stopped early and only 3 patients were enrolled. Therefore, the analysis to evaluate the associations between response and IL-8 as well as VEGF-A was not done.

    Measured: Baseline and 8 weeks

  3. Biospecimen Banking for SNPs Analysis

    To bank biospecimens for the retrospective determination of whether baseline single nucleotide polymorphisms (SNPs) in angiogenesis-related genes predict response to treatment (candidate gene approach). Banking of PBMC is optional but strongly encouraged.

    Note: The SNP genotyping analysis was not performed because the study stopped early and only 3 patients were enrolled. Therefore, the analysis to evaluate the association between baseline SNPs in angiogenesis-related genes and response was not be done.

    Measured: Baseline

  4. Tumor Tissue Banking

    To bank tumor tissue (formalin-fixed, paraffin-embedded tumor blocks) for retrospective examination of the molecular pathophysiologic mediators of tumorigenesis and progression such as phospho-protein expression of MAPK signaling network intermediates in endothelial cells. Banking of tumor tissue is optional but strongly encouraged.

    Note: None of the 3 patients submitted tumor tissues so the analysis won't be performed.

    Measured: Baseline

Timeline

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

  1. First posted25 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJan 2016
  4. Study completionMar 2016

Why it stopped: Closed due to prolonged enrollment timelines

Resources

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01649180
Sponsor's protocol ID
PrE0801
Other IDs
WS1512227
Acronym
PrE0801
Status last verified
Apr 2017
First submitted
21 Jul 2012
Last updated
12 Aug 2021
Data monitoring committee
Yes
Individual data sharing
No: Data is proprietary.

Publications

  • Rini BI, Wilding G, Hudes G, Stadler WM, Kim S, Tarazi J, Rosbrook B, Trask PC, Wood L, Dutcher JP. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol. 2009 Sep 20;27(27):4462-8. doi: 10.1200/JCO.2008.21.7034. Epub 2009 Aug 3.

    PubMed 19652060

  • Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY, McTigue MA, Murray BW, Kania RS, O'Connor P, Shalinsky DR, Bender SL. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83. doi: 10.1158/1078-0432.CCR-08-0652.

    PubMed 19010843

  • Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J, Trask PC, Kim S, Rini BI. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007 Nov;8(11):975-84. doi: 10.1016/S1470-2045(07)70285-1. Epub 2007 Oct 23.

    PubMed 17959415

  • Escudier B, Gore M. Axitinib for the management of metastatic renal cell carcinoma. Drugs R D. 2011;11(2):113-26. doi: 10.2165/11591240-000000000-00000.

    PubMed 21679004

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axitinib in people with Renal Cell Carcinoma, run by PrECOG, 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 33 inclusion and 0 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 12 Aug 2021. 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 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 Apr 2017). 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?

Progression-free Survival (time frame: Assessed every 12 weeks up to 36 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 NCT01649180, which also lists 4 linked publications.

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 12 Aug 2021.

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