Ponatinib in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma
Verified September 2015 by Washington University School of Medicine
Information provided by (Responsible Party):
Washington University School of Medicine
First received: June 25, 2013
Last updated: September 17, 2015
Last verified: September 2015
To test the patient's cancerous tumor to see if it has a FGFR mutation and, if so, to see how their cancer responds to a treatment with the drug ponatinib as well as examine the side effects caused by ponatinib.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Pilot Evaluation of Ponatinib (AP24534), a Potent Oral Pan-FGFR Inhibitor, in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma: a Multi-Institutional Study
Primary Outcome Measures:
- Tumor responses (CR + PR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive)for tumor responses (CR + PR)
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Progression Free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Ponatinib in patients with recurrent or persistent endometrioid endometrial cancer (FGFR2 activating mutation positive) by evaluating progression-free survival
Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Secondary Outcome Measures:
- Progression Free Survival [ Time Frame: 5.5 years ] [ Designated as safety issue: No ]
Progression Free Survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- overall survival [ Time Frame: 5.5 years ] [ Designated as safety issue: No ]
Overall survival is define as date from time of initial treatment to date of death from any cause.
- Toxicity of Ponatinib [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Frequency and severity as defined by CTCAE v 4.0
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||July 2018 (Final data collection date for primary outcome measure)
Ponatinib 45mg po daily for 4 weeks (4 weeks equal 1 cycle).
Ponatinib 45 mg daily for 4 weeks (4 weeks equal one cycle)
Other Name: Iclusig™
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patients must have recurrent or persistent endometrial carcinoma which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma.
- All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or ≥ 10 mm when measured by spiral CT.
Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1 (Section 11.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Patients must have a documented FGFR2 activating mutation either on primary, recurrent or metastatic biopsy. Over 90% of FGFR2 mutations occur at 7 codons. Activating mutations are defined as the known FGFR2 hotspots at S252W, P253R, S373C, Y376C, C383R, N550K, N550H, K660E.
- Patients who have received one or two prior regimen must have a GOG Performance Status of 0, 1, or 2. Patients who have received three prior regimens must have a GOG Performance Status of 0 or 1.
- Patients must be ≥ 18 years of age.
- Patients must be able to swallow tablets.
- Patients must have recovered from the effects of recent surgery, radiotherapy, or chemotherapy.
- Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration.
- Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration.
- Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen. Patients may have received prior anti-angiogenic compounds (i.e., bevacizumab).
Patients are allowed to receive, but are not required to receive, up to two additional cytotoxic regimens for management of recurrent or persistent endometrial disease according to the following definition:
Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa.
Patients must have adequate bone marrow function defined as:
- Absolute neutrophil count (ANC) ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin > 9 g/dl
Patients must have adequate renal function defined as:
• Creatinine ≤ 1.5 x institutional upper limit normal (ULN)
- Proteinuria must be ≤ 3+ by dipstick at baseline. If the urine dipstick is > 3+, a 24-hour protein level must be performed. The 24-hour protein level must be ≤ 3.5 g/24 hours.
Patients must have adequate hepatic function defined as:
- Bilirubin ≤ 1.5 x ULN
- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN
- Albumin ≥ 2.5 g/dl
Patients must have adequate neurologic function defined as:
• Neuropathy (sensory and motor) ≤ grade 1
Patients must have adequate blood coagulation parameters defined as:
- PT such that international normalized ratio (INR) is ≤ 1.5
Patients on therapeutic warfarin are excluded from trial; anticoagulation with a heparin or heparin-like compound is permitted provided patient's PT INR is ≤ 1.5.
- Patients must be able to understand and willing to sign an approved informed consent and authorization permitting release of personal health information.
- Patients of childbearing potential must have a negative serum pregnancy test performed 48 hours prior to first dose and be practicing an effective form of contraception during the study and for at least 3 months after receiving the final treatment of ponatinib. Effective contraception is defined as hormonal or barrier method, or abstinence.
- Patients must have a baseline electrocardiogram completed prior to study entry with QTc ≤ 450 msec. Baseline ECG should be repeated if QTc is found to be > 450 msec. QTc must NOT be > 450 msec on both ECGs performed during the same visit.
Participating institutions will not exclude potential subjects from participating in this or any study solely on the basis of ethnic origin or socioeconomic status. Every attempt will be made to enter all eligible patients into this protocol and therefore address the study objectives in a patient population representative of the entire endometrial cancer population treated by participating institutions.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01888562
|Washington University School of Medicin
|St. Louis, Missouri, United States, 63110 |
|Contact: Matthew Powell, M.D. 314-362-3181 firstname.lastname@example.org |
|Sub-Investigator: David Mutch, M.D. |
|Sub-Investigator: L. Steward Massad, M.D. |
|Sub-Investigator: Premal Thaker, M.D. |
|Sub-Investigator: Andrea Hagemann, M.D. |
|Sub-Investigator: John Pfeifer, M.D., Ph.D. |
|Sub-Investigator: Ian Hagemann, M.D., Ph.D. |
|Sub-Investigator: Nancy Tecu, AOCNP |
Washington University School of Medicine
No publications provided
||Washington University School of Medicine
History of Changes
|Other Study ID Numbers:
|Study First Received:
||June 25, 2013
||September 17, 2015
||United States: Inistitutional Review Board
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 08, 2015
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors