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

NCT01999972 | Completed Phase 1 Results

• 2 other identifiers: A40610682015-001724-31
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 17

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

Carcinoma; Renal Cell

Outcome Measures

Primary Outcomes (1)

• Dose-Escalation Part: Number of Participants With Dose-Limiting Toxicities (DLTs)

  Toxicity as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. DLT defined as any following events attributable to any (axitinib or crizotinib) or both agents in combination: hematologic (Grade 4 neutropenia, absolute neutrophil count\<1000/mm\^3 with single temperature of \>38.3 degrees celsius or sustained temperature of 38 degrees celsius for \>1 hour; \>=Grade 3 neutropenic infection; \>=Grade 3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia), non-hematologic (\>=Grade 3 toxicities \[except asymptomatic hypophosphatemia, hyperuricemia without signs, symptoms of gout, and tumor lysis syndrome\], nausea, vomiting or diarrhea persisted at Grade 3 or 4 despite maximal medical therapy; Grade 3 hypertension if persistent despite anti-hypertensives); In asymptomatic participant, Grade 3 QTc prolongation (QTc\>=501 msec) if persisted after correcting reversible causes, and failure to deliver \>=75 percent (%) of dose of each study drug.

  Cycle 1 (28 days)

Secondary Outcomes (23)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  First dose of study drug until 28 days after last dose (up to 35 cycles in Part 1 and 35 cycles in Part 2, each cycle 28 days)

• Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  First dose of study drug until 28 days after last dose (up to 35 cycles in Part 1 and 35 cycles in Part 2, each cycle 28 days)

• Number of Participants With Grade 3 or Higher Adverse Events (AEs) as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

  First dose of study drug until 28 days after last dose (up to 35 cycles in Part 1 and 35 cycles in Part 2, each cycle 28 days)

• Number of Participants With Clinically Significant Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematological Test Abnormalities

  Baseline up to end of treatment (up to 35 cycles in Part 1 and 35 cycles in Part 2, each cycle 28 days)

• Number of Participants With Clinically Significant Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Biochemistry Test Abnormalities

  Baseline up to end of treatment (up to 35 cycles in Part 1 and 35 cycles in Part 2, each cycle 28 days)

Study Arms (3)

Axitinib in combination with crizotinib, escalation phase

EXPERIMENTAL

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

Drug: axitinib; Drug: crizotinib

Expansion Phase Cohort 1

EXPERIMENTAL

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

Drug: axitinib; Drug: crizotinib

Expansion Phase Cohort 2

EXPERIMENTAL

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

Drug: axitinib; Drug: crizotinib

Interventions

axitinib DRUG

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

Axitinib in combination with crizotinib, escalation phase

crizotinib DRUG

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

Axitinib in combination with crizotinib, escalation phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (17)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Investigational Drug Services IUHSCC

Indianapolis, Indiana, 46202, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Wayne State University, Dept. of Oncology

Detroit, Michigan, 48201, United States

Location

University of Minnesota Health Clinics and Surgery Center

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota Medical Center, Fairview IDS Pharmacy

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota Physicians Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio, 44106, United States

Location

Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

John A Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

University Station Ophthalmology Clinic

Madison, Wisconsin, 53705, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

St Bartholomew's Hospital - Barts Health NHS Trust

London, EC1A 7BE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31171735 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma

Interventions

Axitinib; Crizotinib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperidines; Aminopyridines; Pyridines

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 3, 2013
• Study Start: February 26, 2014
• Primary Completion: February 22, 2017
• Study Completion: September 5, 2019
• Last Updated: September 24, 2020
• Results First Posted: June 21, 2019

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); US (15)