Pazopanib in Molecularly Selected Patients With Advanced NSCLC

NCT02193152 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201408009
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate how participants with advanced non-small cell lung cancer (NSCLC) that have certain abnormalities in the pazopanib target genes respond to pazopanib treatment.

Conditions

Carcinoma, Non-Small Cell Lung; Nonsmall Cell Lung Cancer

Keywords

Advanced Non-Small Cell Lung Cancer; NSCLC; Pazopanib

Outcome Measures

Primary Outcomes (2)

• Response Rate

  * Participants should be re-evaluated for response 8 weeks after initiation of pazopanib and then every 8 weeks thereafter. In addition to a baseline scan, confirmatory scans should also be obtained not less than 4 weeks following initial documentation of objective response. * Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. * Response rate is the percentage of participants with a complete or partial response * Complete response=Disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial response=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

  Until the end of treatment (median length of treatment=85.5 days (full range 25-334 days)

• Progression-free Survival (PFS)

  * Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. There is no limit on following for progression-free survival besides death of the participant. * Progressive disease=At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

  Until progressive disease or death (median follow-up 174 days, full range 41 days-545 days)

Secondary Outcomes (3)

• Outcomes Associated With Specific Mutations

  Until time of death (an expected average of 8 months)

• Mutational Predictors for Extreme Responders

  Until end of treatment (an expected average of 8 months)

• Mechanisms of Secondary Resistance.

  Until the time of progressive disease (an expected average of 8 months)

Study Arms (1)

Treatment: Pazopanib

EXPERIMENTAL

Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal. One cycle of pazopanib is 28 days.

Drug: Pazopanib

Interventions

Pazopanib DRUG

Also known as: GW786034, Votrient®

Treatment: Pazopanib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of advanced (metastatic or unresectable) non-small cell lung cancer (NSCLC) with mutations, rearrangement and fusion involving RET oncogene, or abnormalities in the pazopanib target genes defined as VEGFR1-3, PDGFRA, PDGFRB, or TP53 with abnormalities including deletion, insertion, early stop codon, and/or nonsynonymous mutations with functional consequences. CLIA certified lab testing for pazopanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable.
• Evaluable disease by imaging or physical exam OR measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Failed at least one standard chemotherapeutic treatment for NSCLC.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcl
• Platelets ≥ 100,000/mcl
• Hemoglobin ≥ 9.0 g/dL
• PT or INR ≤ 1.2 x IULN
• aPTT ≤ 1.2 x IULN
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above 1.5 mg/dL
• UPC \< 1 or, if UPC ≥ 1, 24-hour urine protein \< 1 g; use of urine dipstick for renal function assessment is not acceptable.

You may not qualify if:

• Treatment with any of the following anti-cancer therapies:
• Radiation therapy, surgery, or tumor embolization within 14 days prior to the first dose of pazopanib OR
• Chemotherapy, immunotherapy, investigational therapy or hormonal therapy within 14 days prior to the first dose of pazopanib
• Prior treatment with any VEGFR tyrosine kinase inhibitor.
• Administration of any non-oncologic investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of pazopanib.
• Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study treatment
• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Symptomatic brain metastases. Patients with known brain metastases are allowed if they are asymptomatic.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study.
• Any ongoing toxicity from prior anti-cancer therapy that is \> grade 1 and/or that is progressing in severity (except alopecia). Any IO related adverse events must be ≤ grade 1 to be eligible.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled seizure disorder, chronic underlying liver disease unrelated to cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Corrected QT interval (QTc) \> 480 msecs.
• History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina pectoris, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure as defined by the New York Heart Association (see Appendix B).
• Poorly controlled hypertension (defined as systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg). Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure must be reassessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between antihypertensive medication initiation or adjustment and blood pressure measurement. These three values should be averaged to obtain the mean diastolic and systolic blood pressures, which must be \< 140/90 mmHg in order for a patient to be eligible for the study.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other GI conditions with increased risk of perforation, history of abdominal fistula or intra-abdominal abscess within 28 days prior to beginning study treatment.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Novartis: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Daniel Morgensztern, M.D.
• Organization: Washington University School of Medicine

danielmorgensztern@wustl.edu

314-362-5737

Study Officials

• Daniel Morgensztern, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: July 17, 2014
• Study Start: April 27, 2015
• Primary Completion: December 24, 2019
• Study Completion: December 24, 2019
• Last Updated: July 14, 2020
• Results First Posted: July 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)