Phase 2 comparative study of two investigational agents, PF04681502 and PF05212384 respectively, in women with advanced tumour of the uterus.
- Conditions
- RECURRENT ENDOMETRIAL CANCERMedDRA version: 15.0 Level: PT Classification code 10014736 Term: Endometrial cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-003062-32-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 67
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Women aged =18 years.
2. Histologically or cytologically confirmed diagnosis of endometrial carcinoma.
3. Recurrent endometrial cancer that is not amenable to curative surgery and/or radiation.
4. All patients must have tumor tissue available for central analysis of PI3K pathway activation status, performed by the sponsor-identified central laboratory prior to enrollment. Formalin fixed paraffin embedded (FFPE) block preferred, but freshly cut slides are acceptable.
5. Disease progression on or following a platinum containing chemotherapy regimen (alone or in combination with radiation or hormonal therapy) for the treatment of endometrial cancer in the adjuvant or metastatic setting. Patients must not have progression during or immediately following (within approximately 3 months) this regimen.
6. At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, V 1.1. Lesion must not have been previously irradiated.
7. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 (not declining within 2 weeks prior to signing of informed consent).
8. Adequate Bone Marrow Function, including:
a. Absolute Neutrophil Count (ANC) =1,500/mm3 or =1.5 x 1000000000/L.
b. Platelets =100,000/mm3 or =100 x 1000000000/L.
c. Hemoglobin =9 g/dL.
9. Adequate Renal Function, including:
a. Serum creatinine =1.5 x upper limit of normal (ULN) or estimated creatinine clearance = 60 ml/min as calculated using the method standard for the institution.
10. Adequate Liver Function, including:
a. Total serum bilirubin =1.5 x ULN or =1.0 mg/dL.
b. Aspartate and Alanine Aminotransferase (AST & ALT) =2.5 x ULN; =5.0 x ULN if there is liver involvement.
c. Alkaline phosphatase =2.5 x ULN; (=5 x ULN in case of bone metastasis).
11. Adequate blood glucose control, as evidenced by fasting blood glucose of =126 mg/dL.
12. Adequate Cardiac Function, including 12-Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.
13. Resolved acute effects of any prior therapy to baseline severity or Grade =1 CTC AE except for AEs not constituting a safety risk by investigator judgement.
14. Serum/urine pregnancy test (for females of childbearing potential) negative within 72 hours of starting treatment. For
patients participating in the PK lead in sub-study, pregnancy test must be performed before the single dose (within 72 hours prior).
Female patients must be surgically sterile or be postmenopausal, or must agree to use highly effective contraception during the period of the trial and for at least 90 days after completion of treatment. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):
- Have undergone hysterectomy or bilateral oophorectomy
Patients presenting with any of the following will not be included in the study:
1. Patients who are investigational site staff members and directly involved with the conduct of the trial or patients who are Pfizer employees directly involved in the conduct of the trial.
2. More than 2 prior cytotoxic chemotherapy regimens for endometrial carcinoma in the adjuvant or metastatic setting. Prior hormonal or biologic therapy is acceptable.
3. Patients with known active brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
4. Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), hormonal, biological or investigational agents within 2 weeks of first dose of study drug (6 weeks for mitomycin C or nitrosoureas).
5. Any surgery (not including minor procedures such as lymph node biopsy, needle biopsy, and/or placement of port-a-cath) within 4 weeks of first dose of study drug; or not fully recovered from any side effects of previous procedures.
6. Prior therapy with an agent that is known or proposed to be active by action on PI3K, and/or mTOR, and/or AKT.
7. Uncontrolled diabetes mellitus defined as HbA1c >8%.
8. Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors. Because inhibition of CYP3A4 isoenzymes may increase study drug exposure leading to a potential increases in toxicities, the use of known strong inhibitors (Strong CYP3A4 Inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits (eg, Seville oranges, pomelos), ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, erythromycin, clarithromycin, telithromycin, varapamil, indinavir, saquinavir, ritonavir, nelfinavir, nefazodone, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine, troleandomycin, mibefradil, conivaptan) are not permitted from 10 days prior to the first dose of study drug until study treatment discontinuation.
9. Current or anticipated need for food or drugs that are known potent CYP3A4 inducers. Study drug metabolism may be induced when taking strong CYP3A4 inducers (eg, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, St. John’s Wort) resulting in reduced plasma concentrations. Therefore co administration of study drug in combination with these and other strong CYP3A4 inducers is not permitted from 10 days prior to the first dose of stud drug until study treatment discontinuation.
10. Concurrent administration of herbal preparations.
11. Breast feeding: No studies have been conducted in humans to assess the impact of PF 04691502 or PF-05212384 on milk production, its presence in breast milk and its effects on the breast fed child. Because drugs are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, lactating female patients are excluded from this study.
12. Any clinic
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method