A Phase 1b Study Of Axitinib In Combination With Crizotinib In Patients With Advanced Solid Tumors

NCT ID: NCT01999972

Last Updated: 2020-09-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-26

Study Completion Date

2019-09-05

Brief Summary

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Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment, while the majority of patients will eventually develop evasive resistance. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute to VEGF inhibitor resistance, such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with the VEGF inhibitor, axitinib.Since this will be the first study of axitinib given in combination with crizotinib, the study will primarily assess the safety and tolerability of the combination regimen.

Detailed Description

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Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Axitinib in combination with crizotinib, escalation phase

Dose Escalation Advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available

Group Type EXPERIMENTAL

axitinib

Intervention Type DRUG

Axitinib: tablets, dosage range 2 - 5 mg, given orally twice daily on a continuous dosing schedule in 28 days cycles.

crizotinib

Intervention Type DRUG

Crizotinib: capsules, dosage range 200-250 mg, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Expansion Phase Cohort 1

Dose Expansion, Cohort 1: axitinib in combination with crizotinib Advanced renal cell cancer \[RCC\] with no prior systemic therapy

Group Type EXPERIMENTAL

axitinib

Intervention Type DRUG

Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.

crizotinib

Intervention Type DRUG

Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Expansion Phase Cohort 2

Dose Expansion, Cohort 2: axitinib in combination with crizotinib Advanced renal cell cancer with at least one but no more than two prior systemic treatment regimens directed at advanced RCC

Group Type EXPERIMENTAL

axitinib

Intervention Type DRUG

Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.

crizotinib

Intervention Type DRUG

Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Interventions

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axitinib

Axitinib: tablets, dosage range 2 - 5 mg, given orally twice daily on a continuous dosing schedule in 28 days cycles.

Intervention Type DRUG

crizotinib

Crizotinib: capsules, dosage range 200-250 mg, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Intervention Type DRUG

axitinib

Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.

Intervention Type DRUG

crizotinib

Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Intervention Type DRUG

axitinib

Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.

Intervention Type DRUG

crizotinib

Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosis - Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available.
* Diagnosis - Dose Expansion Phase: Histologically or cytologically confirmed advanced RCC with a component of clear cell subtype
* Dose Expansion Phase: at least one measureable lesion as defined by RECIST \[Response Evaluation Criterion in Solid Tumors\] version 1.1.
* ECOG \[Eastern Cooperative Oncology Group\] Performance Status 0 or 1.

Exclusion Criteria

* Major surgery \<4 weeks or radiation therapy \<2 weeks of patient registration.
* History of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
* Dose Expansion Phase only: diagnosis of any other malignancy within 2 years prior to registration.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Investigational Drug Services IUHSCC

Indianapolis, Indiana, United States

Site Status

IU Health University Hospital

Indianapolis, Indiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Wayne State University, Dept. of Oncology

Detroit, Michigan, United States

Site Status

University of Minnesota Health Clinics and Surgery Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center, Fairview IDS Pharmacy

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Physicians Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio, United States

Site Status

Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

John A Moran Eye Center

Salt Lake City, Utah, United States

Site Status

University Station Ophthalmology Clinic

Madison, Wisconsin, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

St Bartholomew's Hospital - Barts Health NHS Trust

London, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital

London, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Michaelson MD, Gupta S, Agarwal N, Szmulewitz R, Powles T, Pili R, Bruce JY, Vaishampayan U, Larkin J, Rosbrook B, Wang E, Murphy D, Wang P, Lechuga MJ, Valota O, Shepard DR. A Phase Ib Study of Axitinib in Combination with Crizotinib in Patients with Metastatic Renal Cell Cancer or Other Advanced Solid Tumors. Oncologist. 2019 Sep;24(9):1151-e817. doi: 10.1634/theoncologist.2018-0749. Epub 2019 Jun 6.

Reference Type DERIVED
PMID: 31171735 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2015-001724-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A4061068

Identifier Type: -

Identifier Source: org_study_id

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