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NCT02272998

Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.

Completed Phase 2 Results posted Last updated 24 March 2025
What this trial tests

Phase 2 trial testing ponatinib hydrochloride in Malignant Neoplasm in 22 participants. Completed in 17 November 2022.

Timeline
24 February 2015
Primary endpoint
17 November 2022
17 November 2022

Quick facts

Lead sponsorSameek Roychowdhury
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment22
Start date24 February 2015
Primary completion17 November 2022
Estimated completion17 November 2022
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sameek Roychowdhury

Who can join

18 and older, any sex, with Malignant Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment Primary · Up to 6 months

The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses. Response for tumors was assessed using the RECIST 1.1 criteria (using computed tomography \[CT\] scans), where response was defined as a partial or complete response.

GroupValue95% CI
Participants With Genomic Alterations in FGFR1
Participants With Genomic Alterations in Rare Genomic Targets (KIT, PDGFRα, RET, ABL1, and FLT3)0
Percentage of Participants With Adverse Events, Defined as Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Secondary · Up to 30 days after last dose of study drug, up to a total of 6 years

Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

Dry Skin, Grade 1
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)36.4
Dry Skin, Grade 2
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)4.6
Dry Skin, Grade ≥3
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)9.1
Rash Maculo-papular, Grade 1
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)27.3
Rash Maculo-papular, Grade 2
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)9.1
Hypertension, Grade 1
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)4.6
Hypertension, Grade 2
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)9.1
Hypertension, Grade ≥3
GroupValue95% CI
Treatment (Ponatinib Hydrochloride)13.6
Tolerability of the Regimen, Assessed by the Number of Patients Who Required Dose Modifications and/or Dose Delays Secondary · Up to 30 days after last dose of study drug

Collected and summarized by descriptive statistics.

GroupValue95% CI
Treatment (Ponatinib Hydrochloride)11
Overall Survival Secondary · The time from treatment initiation to death, assessed up to 72 months

Kaplan-Meier curves will be used to estimate the survival distribution.

GroupValue95% CI
Treatment (Ponatinib Hydrochloride)5.30 – 72
Progression Free Survival Secondary · The time from treatment initiation to progression or death, assessed up to 2 years

Kaplan-Meier curves will be used to estimate the survival distribution.

GroupValue95% CI
Treatment (Ponatinib Hydrochloride)1.90 – 19.7
Clinical Benefit Rate (CBR) Secondary · 6 months

Calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for CBR will be calculated.

GroupValue95% CI
Treatment (Ponatinib Hydrochloride)31.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected for each patient from the start of treatment with the investigational drug up to 30 days after ending treatment. The total time period in which adverse event data was collected for this study was 6 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Ponatinib Hydrochloride)
Serious: 3/22 (14%)
Deaths: 16/22

Serious adverse events (4 terms)

ReactionSystemTreatment (Ponatinib Hydro…
Abdominal painGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
AscitesGastrointestinal disorders
Thromboembolic EventVascular disorders
Other adverse events (65 terms — click to expand)

ReactionSystemTreatment (Ponatinib Hydro…
FatigueGeneral disorders
ConstipationGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
DyspneaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Weight LossInvestigations
Back painMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
HypertensionVascular disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Abdominal PainGastrointestinal disorders
HeadacheNervous system disorders
HyperglycemiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
InsomniaPsychiatric disorders
Lymphocyte count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Dry mouthGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
VomitingGastrointestinal disorders
Eye disorders, otherEye disorders
HypoalbuminemiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
Non-cardiac chest painGeneral disorders
DehydrationMetabolism and nutrition disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
HyponatremiaMetabolism and nutrition disorders
Mucositis oralGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
AscitesGastrointestinal disorders
Creatinine increasedInvestigations
DizzinessNervous system disorders

Most-reported serious reactions: Abdominal pain, Anorexia, Ascites, Thromboembolic Event.

Data from ClinicalTrials.gov NCT02272998 adverse events section.

Sponsor's own description

This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies.
    Tan FH, Putoczki TL, Stylli SS, Luwor RB. · · 2019 · cited 142× · PMID 30705592 · DOI 10.2147/ott.s189391
  2. Translating cancer genomes and transcriptomes for precision oncology.
    Roychowdhury S, Chinnaiyan AM. · · 2016 · cited 125× · PMID 26528881 · DOI 10.3322/caac.21329
  3. FGFR3-TACC3 fusion in solid tumors: mini review.
    Costa R, Carneiro BA, Taxter T, Tavora FA, et al · · 2016 · cited 107× · PMID 27409839 · DOI 10.18632/oncotarget.10482
  4. FGFR-TKI resistance in cancer: current status and perspectives.
    Yue S, Li Y, Chen X, Wang J, et al · · 2021 · cited 98× · PMID 33568192 · DOI 10.1186/s13045-021-01040-2
  5. FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention.
    De Luca A, Esposito Abate R, Rachiglio AM, Maiello MR, et al · · 2020 · cited 87× · PMID 32962091 · DOI 10.3390/ijms21186856
  6. Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting.
    Farrell B, Breeze AL. · · 2018 · cited 77× · PMID 30545934 · DOI 10.1042/bst20180004
  7. Therapy of Primary Liver Cancer.
    Feng M, Pan Y, Kong R, Shu S. · · 2020 · cited 71× · PMID 32914142 · DOI 10.1016/j.xinn.2020.100032
  8. Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies.
    Lang L, Teng Y. · · 2019 · cited 68× · PMID 30634399 · DOI 10.3390/cells8010031

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Other recruiting trials for Malignant Neoplasm

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