AzTrials
AzTrials

Endometrial Adenosquamous CarcinomaPhase 2NCT01935934

Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

A Phase 2 study testing Cabozantinib S-malate, Laboratory Biomarker Analysis and Pharmacological Study in people with Endometrial Adenosquamous Carcinoma and Endometrial Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well cabozantinib s-malate works in treating patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Cabozantinib S-malate, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
19 sitesin 2 countries
Study dates
8 May 2013to 24 Oct 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed metastatic endometrial cancer; eligible histologies for the experimental cohort are: endometrioid or serous; eligible histologies for the exploratory cohort are: carcinosarcoma, clear cell, mixed, adenosquamous and any other rare sub-type of endometrial cancer
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam and >= 15 mm in short axis for nodal lesions; patients must have radiographic evidence of disease progression following the most recent line of treatment
  • Prior therapy: Eligible subjects must have had 1 line of systemic cytotoxic treatment; this may be adjuvant therapy with documented progression within 12 months of completion, or 1 line of cytotoxic therapy for metastatic disease; NOTE: eligible patients are allowed up to 2 lines of systemic cytotoxic treatment, of which only 1 line is allowed for metastatic disease; the acceptance of progression within 12 months of adjuvant is part inclusion to not require patient to re-challenge with chemotherapy (chemo) if they progressed soon after adjuvant therapy; prior hormonal therapy for metastatic/recurrent disease is also allowed; prior targeted therapy not directed against cMET or vascular endothelial growth factor (VEGF) pathways is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1.5 x 10^9/L
Show all 19Show fewer
  • Platelets >= 100 x 10^9/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
  • Creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Hemoglobin >= 90 g/L
  • Serum albumin >= 28 g/L
  • Lipase < 2.0 x ULN; no radiologic/clinical evidence of pancreatitis
  • Urine protein/creatinine ratio (UPCR) =< 1
  • Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
  • Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopausal is defined as amenorrhea >= 12 consecutive months; note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
  • Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)
  • Patients must consent to analysis on archival tissue; if archival sample is not available, a sufficient tumor biopsy can be performed a minimum of 28 days prior to start of treatment if felt to be clinically reasonable
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g., cytokines or antibodies) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Prior treatment with cabozantinib
  • The subject has received radiation therapy:
  • To bone metastasis within 14 days before the first dose of study treatment
  • To any other site(s) within 28 days before the first dose of study treatment
  • The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Show all 58Show fewer
  • The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
  • The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from related toxicity to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
  • 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 cancer
  • Patients with known brain metastases should be excluded from this clinical trial
  • The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN =< 7 days before the first dose of study treatment
  • Therapeutic anticoagulation with warfarin, antiplatelet agents (e.g., clopidogrel), thrombin, or Factor Xa inhibitors is not allowed; therapeutic anticoagulation with low molecular weight heparin (LMWH) is allowed as well as prophylactic anticoagulation using low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and LMWH
  • The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)
  • The subject has 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
  • The subject has tumor in contact with, invading or encasing any major blood vessels
  • The subject has evidence of tumor invading the gastrointestinal (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
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including:
  • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
  • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
  • Any history of congenital long QT syndrome
  • Any of the following within 6 months before the first dose of study treatment:
  • Unstable angina pectoris
  • Clinically-significant cardiac arrhythmias
  • Stroke (including transient ischemic attack [TIA], or other ischemic event)
  • Myocardial infarction
  • Thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
  • Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Any of the following within 28 days before the first dose of study treatment
  • Intra-abdominal tumor/metastases invading GI mucosa
  • Active peptic ulcer disease,
  • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
  • Malabsorption syndrome
  • Any of the following within 6 months before the first dose of study treatment:
  • Abdominal fistula
  • Gastrointestinal perforation
  • Bowel obstruction or gastric outlet obstruction
  • Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment
  • Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
  • Other clinically significant disorders such as:
  • Active uncontrolled infection requiring intravenous systemic treatment within 14 days before the first dose of study treatment
  • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
  • History of organ transplant
  • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
  • History of major surgery as follows:
  • Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
  • Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications
  • In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
  • The subject is unable to swallow tablets
  • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms =< 7 days before the first dose of study treatment
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to XL184
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with XL184
  • Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

United States12 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • UPMC-Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

Other trials in United States

Canada7 sites

  • Arthur J E Child Comprehensive Cancer Centre

    Calgary, Alberta, T2N 5G2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Ottawa Hospital and Cancer Center-General Campus

    Ottawa, Ontario, K1H 8L6

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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

This phase II trial studies how well cabozantinib s-malate works in treating patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine efficacy of single agent cabozantinib s-malate (cabozantinib) in women previously receiving one line of chemotherapy for metastatic endometrial cancer or with progression within 12 months of completing adjuvant therapy, with co-primary endpoints of objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and progression-free-survival at 12 weeks (PFS).

SECONDARY OBJECTIVES:

  1. Correlation of clinical response with baseline molecular status of archival tumor (hepatocyte growth factor receptor [c-met] amplification \& mutation status) and overall survival.

OUTLINE:

Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks or every 6 months.

Being tested
Cabozantinib S-malate, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Carcinoma, Endometrioid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL 184

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01935934
Study groupRoleWhat they receive
Treatment (cabozantinib s-malate)ExperimentalPatients receive 60 mg cabozantinib s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response Rate

    Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: At 12 weeks, then every 8 weeks during treatment; up to 12 weeks post-treatment if discontinued due to toxicities, a maximum of 16 weeks

  2. Progression-free Survival

    Defined as the percentage of patients progression free 12 weeks from starting treatment.

    Measured: Time from start of treatment to time of progression or death, assessed at 12 weeks

Secondary outcomes (2)

  1. Number of Participants With Archival Specimens That Had C-met Amplification or Mutation

    Will correlate with clinical response.

    83 tumors were profiled on the NGS TruSeq amplicon panel and 1 on Sequenom. Fields with at least 50 tumor cells were captured to analyze 100 non-overlapping tumor cell nuclei to calculate a ratio of MET to CEP7 signal; MET ampliction was defined as MET/CEP7 ratio >=2.

    Measured: Baseline

  2. Overall Survival

    Will correlate with clinical response.

    Measured: Time from start of treatment to time of death, every 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2013 (estimated)
  2. Study start8 May 2013
  3. Primary completion12 Sep 2019
  4. Study completion24 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01935934
Sponsor's protocol ID
NCI-2013-00890
Other IDs
NCI-2013-00890, PHL-086, 9322, 9322, N01CM00032, N01CM00038, N01CM00071, UM1CA186644
Status last verified
Sep 2025
First submitted
3 Sep 2013
Last updated
1 Oct 2025
Data monitoring committee
No

Publications

  • Dhani NC, Hirte HW, Wang L, Burnier JV, Jain A, Butler MO, Welch S, Fleming GF, Hurteau J, Matsuo K, Matei D, Jimenez W, Johnston C, Cristea M, Tonkin K, Ghatage P, Lheureux S, Mehta A, Quintos J, Tan Q, Kamel-Reid S, Ludkovski O, Tsao MS, Wright JJ, Oza AM. Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86). Clin Cancer Res. 2020 Jun 1;26(11):2477-2486. doi: 10.1158/1078-0432.CCR-19-2576. Epub 2020 Jan 28.

    PubMed 31992589

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib S-malate, Laboratory Biomarker Analysis and Pharmacological Study in people with Endometrial Adenosquamous Carcinoma and Endometrial Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (time frame: At 12 weeks, then every 8 weeks during treatment; up to 12 weeks post-treatment if discontinued due to toxicities, a maximum of 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01935934, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in