Ponatinib in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma

NCT01888562 | Withdrawn

• 1 other identifier: 201404024
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Endometrial Neoplasms

Outcome Measures

Primary Outcomes (2)

• Tumor responses (CR + PR)

  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.

  6 months

• Progression Free survival

  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.

  6 months

Secondary Outcomes (3)

• Progression Free Survival

  5.5 years

• overall survival

  5.5 years

• Toxicity of Ponatinib

  1 year

Study Arms (1)

Ponatinib

EXPERIMENTAL

Ponatinib 45mg po daily for 4 weeks (4 weeks equal 1 cycle).

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib 45 mg daily for 4 weeks (4 weeks equal one cycle)

Also known as: Iclusig™

Ponatinib

Eligibility Criteria

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

You may qualify if:

• 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:

You may not qualify if:

• Patients must not have had prior therapy with ponatinib or anti-FGFR (fibroblast growth factor receptor) therapy including brivanib, BIBF1120, and E7080.
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, localized cancer of the breast, and localized cancer of the head and neck, are excluded if there is any evidence of the other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.
• Patients must not be on required chronic anti-platelet therapy (aspirin \>300 mg/day, or clopidogrel greater than or equal to 75mg/day).
• Patients must not have any gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 within 30 days prior to study entry.
• Patients must not have a history of poor wound healing, non-healing ulcers or bone fractures within the last 3 months.
• Patients must not have uncontrolled or significant cardiovascular disease including:
• Myocardial infarction within 3 months
• Uncontrolled angina within 3 months
• Class III-IV New York Heart Association (NYHA) congestive heart failure (see Appendix B)
• Uncontrolled hypertension (systolic BP \> 150 or diastolic BP \> 100 mmHg for 24 hours) despite optimized anti-hypertensive therapy. BP must be below 150/100 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 inhibitors should be changed to an alternative antihypertensive medication before study entry
• History of stroke, TIA, or other CNS ischemic event
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Pre-therapy Left Ventricle Ejection Fraction (LVEF) ≤ 50%

Sponsors & Collaborators

• Washington University School of Medicine: lead

Related Links

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

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Matthew Powell, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: June 27, 2013
• Study Start: January 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2023
• Last Updated: December 18, 2015

Record last verified: 2015-12