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Non-small Cell Lung CancerPhase 1/2NCT01728181

A Phase I/II Study of Tivozanib and Erlotinib as Initial Treatment for Metastatic Non-small Cell Lung Cancer Assigned by VeriStrat® Serum Proteomic Evaluation

A Phase 1/2 study testing Tivozanib and Erlotinib in people with Non-small Cell Lung Cancer and Stage IV Disease, run by University of Utah.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The current trial "A Phase I/II study of Erlotinib +/- Tivozanib as initial treatment for Metastatic Non-small Cell Lung Cancer assigned by VeriStrat® Serum Proteomic Evaluation" will begin by evaluating toxicity for the combination of Tivozanib and Erlotinib to determine a phase II dose. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tivozanib and Erlotinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Nov 2013to Mar 2016
Phase
Phase 1/2
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

  • Histological or cytological diagnosis of non-squamous, non-small cell lung cancer.
  • Stage IV disease.
  • Age > 18
  • If female and of childbearing potential, documentation of negative pregnancy test within 7 days prior to first dose.
  • Sexually active women of childbearing potential must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug. All fertile female subjects (and their partners) must agree to use a highly effective method of contraception. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study).
  • Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
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  • Additional Phase II Inclusion Criteria:
  • -No prior treatment for metastatic disease (Phase II ONLY). Patients who received adjuvant systemic chemotherapy are eligible if greater than 6 months has elapsed.
  • Prior erlotinib treatment is allowed in phase I.
  • Performance status of 0-1.
  • One disease site meeting RECIST (version 1.1) criteria for measurable or non-measurable disease. Disease sites measured from the CT portion of a combined PET/CT may be used to document measurable disease (Liver or PET findings may be used only for non-measurable disease).

Who cannot join

  • Significant cardiovascular disease, including:
  • Active, clinically symptomatic left ventricular failure.
  • Uncontrolled hypertension: Systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart.
  • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
  • Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
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  • Coronary or peripheral artery bypass graft within 6 months of screening.
  • Uncontrolled CNS metastases are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicity of radiation has resolved and steroids are no longer required. Leptomeningeal metastases are not allowed.
  • Any of the following hematologic abnormalities:
  • Hemoglobin < 9.0 g/dL
  • Absolute neutrophil count (ANC) < 1500 per mm3
  • Platelet count < 100,000 per mm3
  • INR >1.5 or PTT >1.5 × ULN
  • Any of the following serum chemistry abnormalities:
  • Total bilirubin > 1.5 × ULN (or > 2.5 × ULN for subjects with Gilbert's syndrome)
  • AST or ALT > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
  • Creatinine > 2.0 × ULN
  • Proteinuria > 3+ by urinalysis or urine dipstick
  • Non-healing wound, bone fracture, or skin ulcer.
  • Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
  • Serious/active infection or infection requiring parenteral antibiotics.
  • Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
  • Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Peripheral arterial ischemia > Grade 2 (per CTCAE Version 4.0)
  • Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
  • Hematemesis, hematochezia, melena or other gastrointestinal bleeding > Grade 2 (per CTCAE Version 4.0)
  • Hemoptysis or other pulmonary bleeding (> 1/2 tsp/event over last 3 months not associated with bronchoscopy)
  • Hematuria or other genitourinary bleeding > Grade 2 (per CTCAE Version 4.0)
  • Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.
  • Pregnant or lactating females.
  • History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant.
  • Life-threatening illness or organ system dysfunction compromising safety evaluation.
  • Requirement for hemodialysis or peritoneal dialysis.
  • Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib, major resection of the stomach or small bowel, or gastric bypass procedure.
  • Psychiatric disorder or altered mental status precluding informed consent or protocol related testing.

About this study

The current trial "A Phase I/II study of Erlotinib +/- Tivozanib as initial treatment for Metastatic Non-small Cell Lung Cancer assigned by VeriStrat® Serum Proteomic Evaluation" will begin by evaluating toxicity for the combination of Tivozanib and Erlotinib to determine a phase II dose. The phase II portion of the study will seek to duplicate the finding of the BEER trial in a selected population of patients with NSCLC with a VeriStrat® Good signature using two oral agents with Tivozanib substituted for bevacizumab. Phase II will be designed as a selection-based randomized trial. Patients with VeriStrat® Good signature will be assigned to EGFR inhibitor therapy with a randomization to Erlotinib plus/minus Tivozanib. Patients with VeriStrat® Poor signature will be assigned to standard of care. Standard-of-care chemotherapy as first treatment at the discretion of patient and physician will be evaluated for response to treatment, survival and repeat VeriStrat® signature.

Being tested
Tivozanib, Erlotinib, Standard of Care treatment
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Disease

What participants receive

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

  • TivozanibDrug

    Also called AV-951, KRN951

    The phase I study will test two dose levels of tivozanib (dose level 1: 1.0 mg and dose level 2: 1.5 mg) given daily for 3 consecutive weeks followed by one week break. Based on the phase I results, the dose of tivozanib will be chosen for the phase II study.

  • ErlotinibDrug

    150 mg/day for 28 day cycle. No rest period.

  • Standard of Care treatmentOther

    This treatment will be determined by the study doctor and is considered standard of care.

Study groups in NCT01728181
Study groupRoleWhat they receive
Phase IExperimentalWill receive Tivozanib and Erlotinib treatment.
Receives: Drug: Tivozanib; Drug: Erlotinib
Phase II Group 1 (Standard of Care)OtherGroup 1: VeriStrat® predicts the chance of no benefit from erlotinib • The patient will get standard-of- care
Receives: Other: Standard of Care treatment
Phase II Group 2 (arm 1)Active comparatorGroup 2: VeriStrat® predicts the chance of benefit from Erlotinib • Arm 1: Patient will get the study drugs Erlotinib and Tivozanib
Receives: Drug: Tivozanib; Drug: Erlotinib
Phase II Group 2 (arm 2)Placebo comparatorGroup 2: VeriStrat® predicts the chance of benefit from Erlotinib • Arm 2: Patient will get the study drug erlotinib and placebo
Receives: Drug: Erlotinib

What is being measured

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

  1. Safety of combination tivozanib and erlotinib

    Phase I- To define the safety (maximum tolerated dose) of Tivozanib when administered in combination with Erlotinib in patients with NSCL cancer.

    Measured: 36 months

  2. Overall Survival

    Phase II - Overall survival for selection strategy of Erlotinib +/- Tivozanib

    Measured: 36 months

Secondary outcomes (1)

  1. Overall Survival for entire population

    Measured: 36 months

Timeline

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

  1. First posted16 Nov 2012 (estimated)
  2. Study startNov 2013
  3. Primary completionMar 2016 (estimated)
  4. Study completionMar 2016 (estimated)

Why it stopped: Stopped before approval due to ineffective drug

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01728181
Sponsor's protocol ID
HCI59004
Status last verified
Jul 2013
First submitted
12 Nov 2012
Last updated
25 Jul 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tivozanib and Erlotinib in people with Non-small Cell Lung Cancer and Stage IV Disease, run by University of Utah.

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 11 inclusion and 36 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: withdrawn, as of the sponsor's last update on 25 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Safety of combination tivozanib and erlotinib (time frame: 36 months). The study lists 2 primary outcomes in all. 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 NCT01728181.

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 25 Jul 2013.

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