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A Phase 2 Study of XL184 (Cabozantinib) in Recurrent or Metastatic Endometrial Cancer

Phase 2
18 Years
Not Enrolling
Metastatic, Endometrial Cancer, Endometrioid, Serous, Mix Histology, Carcinosarcoma, Clear Cell, Adenosquamous

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Trial Information

A Phase 2 Study of XL184 (Cabozantinib) in Recurrent or Metastatic Endometrial Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic endometrial cancer with one of
the following histologies: endometrioid, serous, carcinosarcoma, clear cell,
adenosquamous, or mixed histology.

- Measurable disease.

- Prior therapy: May have received adjuvant therapy (chemo- and/or radiation) and must
have received one (1) prior line of cytotoxic therapy for recurrent or metastatic
disease. Prior hormonal therapy for metastatic/recurrent disease is also allowed.
Prior targeted therapy which does not target cMET or VEGF pathways is allowed.
Patients who progress within 6-12months of adjuvant treatment completion are eligible
without additional lines of treatment.

- Age ≥18 years on day of consent.

- ECOG performance status <2 (Karnofsky >60%).

- Life expectancy of greater than 3 months..

- Must have normal organ and marrow function.

- Women of childbearing potential must not be pregnant and must agree to use adequate
contraception prior to study entry and for the duration of study participation.

- Must consent to analysis on archival tissue; if archival sample is not available, a
tumour biopsy will be done.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Received cytotoxic chemotherapy or biologic agents within 3 weeks, or nitrosoureas/
mitomycin C within 6 weeks before the first dose of study treatment.

- Prior treatment with cabozantinib.

- Received radiation therapy: to the thoracic cavity, abdomen, or pelvis within 3
months before the first dose of study treatment, or has ongoing complications, or is
without complete recovery and healing from prior radiation therapy; to bone
metastasis within 14 days before the first dose of study treatment; or to any other
site(s) within 28 days before the first dose of study treatment.

- Received radionuclide treatment within 6 weeks of the first dose of study treatment.

- Received prior treatment with a small molecule kinase inhibitor or a hormonal therapy
within 14 days or five half-lives of the compound or active metabolites, whichever is
longer, before the first dose of study treatment.

- Received any other type of investigational agent within 28 days before the first dose
of study treatment.

- Has not recovered to baseline or CTCAE ≤ Grade 1 from related toxicity to all prior
therapies except hair loss (alopecia) and other non-clinically significant side

- Any other prior malignancy from which the patient has been disease free for less than
3 years, with the exception of adequately treated and cured basal or squamous cell
skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other

- Known brain metastases.

- Prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin
time (PTT) test ≥1.3 the laboratory ULN within 7 days before the first dose of study

- Requires concomitant treatment in therapeutic doses, with anticoagulants such as
warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or
antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤81 mg/day), low-dose
warfarin (≤1 mg/day), and prophylactic low molecular weight heparin (LMWH) are

- Requires chronic concomitant treatment of strong CYP3A4 inducers (e.g.,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,
phenobarbital, and St. John's Wort).

- Experienced any of the following: clinically-significant gastrointestinal bleeding
within 6 months before the first dose of study treatment; hemoptysis of ≥0.5 teaspoon
(2.5 mL) of red blood within 3 months before the first dose of study treatment; any
other signs indicative of pulmonary hemorrhage within 3 months before the first dose
of study treatment

- Radiographic evidence of cavitating pulmonary lesion(s).

- Tumor in contact with, invading or encasing any major blood vessels.

- Evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel,
rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28
days before the first dose of cabozantinib.

- Uncontrolled, significant intercurrent or recent illness including, but not limited
to, the following conditions:

- Cardiovascular disorders

- Gastrointestinal disorders particularly those associated with a high risk of
perforation or fistula formation

- Other disorders associated with a high risk of fistula formation including PEG
tube placement within 3 months before the first dose of study therapy

- Other clinically significant disorders

- Is unable to swallow tablets.

- Has a corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms
within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms,
two additional EKGs separated by at least 3 minutes should be performed. If the
average of these three consecutive results for QTcF is ≤500 ms, the patient meets
eligibility in this regard.

- Unable or unwilling to abide by the study protocol or cooperate fully with the
investigator or designee.

- Evidence within 2 years of the start of study treatment of another malignancy which
required systemic treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to XL184

- Pregnant or breastfeeding

- HIV-positive

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with an objective response

Outcome Description:

Per RECIST 1.1

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Amit Oza, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Cancer Centre


Canada: Health Canada

Study ID:

PHL-086 / NCI 9322



Start Date:

April 2013

Completion Date:

September 2015

Related Keywords:

  • Metastatic
  • Endometrial Cancer
  • Endometrioid
  • Serous
  • Mix Histology
  • Carcinosarcoma
  • Clear Cell
  • Adenosquamous
  • metastatic
  • endometrial cancer
  • endometrioid
  • serous
  • mix histology
  • carcinosarcoma
  • clear cell
  • adenosquamous
  • XL184
  • cabozantinib
  • MET amplification
  • receptor tyrosine kinases
  • RTK
  • pharmacokinetics
  • Endometrial Neoplasms
  • Sarcoma, Endometrial Stromal
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Adenoma