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Bile Duct CancerPhase 2NCT01954745

Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

A Phase 2 study testing Cabozantinib in people with Bile Duct Cancer and Intrahepatic Cholangiocarcinoma, run by Massachusetts General Hospital at 3 sites in United States.

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 research study is evaluating a drug called cabozantinib as a possible treatment cancer of the bile duct. Cabozantinib is a drug that targets specific pathways inside the cells of the body. By blocking the c-MET and VEGFR2 pathways from sending signals, cabozantinib may prevent cells from multiplying. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
3 sitesUnited States
Study dates
Sep 2013to Jun 2016
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (i.e. hilar and distal cholangiocarcinoma).
  • Participants 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) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
  • Participants must have failed at least 1 but no more than 2 lines of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
  • Age ≥ 18 years.
  • Life expectancy of ≥ 3 months.
  • ECOG performance status < 1 (see Appendix A).
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  • Participants must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 2.0 x the upper limit of normal
  • AST (SGOT)/ALT (SGPT) ≤ 5 X institutional upper limit of normal
  • PT/PTT ≤ 1.5 x ULN
  • Creatinine ≤ 1.5 or GFR ≥ 60 mL/min/1.73m2
  • Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
  • Serum phosphorus, calcium, magnesium and potassium ≥ LLN
  • Urine protein: creatinine ratio ≤ 1
  • Serum Albumin ≥ 2.8 g/dl
  • Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside of the treated area or measurable progression at the site of the treated area
  • Ability to understand and the willingness to sign a written informed consent document.
  • Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, 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).
  • 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. Postmenopause 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.

Who cannot join

  • Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
  • Prior treatment with cabozantinib or other VEGF-R directed therapies
  • Gallbladder carcinoma or periampullary tumors
  • Chemotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin) or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • The subject has received radiation therapy:
  • to the thoracic cavity, abdomen or pelvis within 3 months of the first dose of study treatment or has with ongoing complications or is without complete recovery and healing from prior radiation therapy
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  • to bone or brain metastasis within 14 days of the first dose of study treatment
  • to any other site(s) within 28 days of the first dose of study treatment
  • The subject has a primary brain tumor.
  • The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.)
  • 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 BP > 140 mm Hg systolic, or > 90 mm Hg 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 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 that 6 months before the first dose of study treatment.
  • 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 such as:
  • active infection requiring systemic treatment within 28 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 months 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
  • Clinically significant gastrointestinal bleeding within six months of the first dose of study treatment
  • Previous history of pulmonary embolism or deep venous thrombosis
  • Severely impaired lung function or history of interstitial lung disease
  • Concurrent malignancy (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder, and cervical carcinoma in situ) diagnosed within the past 3 years or any currently active malignancy
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • The subject has a history of clinically significant hematemesis, hemoptysis of > 2.5 mL of red blood, radiation (including brachytherapy) to pulmonary lesions, or signs indicative of significant pulmonary hemorrhage within 3 months before the first dose of study treatment.
  • The subject has radiographic evidence of cavitating pulmonary lesion(s)
  • The subject has a lesion abutting, invading, or encasing a major blood vessel.
  • The subject has 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.
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
  • The subject 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 subject meets eligibility in this regard
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib.
  • The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin, warafarin-related agents, heparin, thrombin inhibitors, Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic Low Molecular Weight Heparin (LMWH) are permitted.
  • The subject requires concomitant use of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, and ritonavir).
  • 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. Note: Subjects with prostate cancer currently receiving LHRH or GnRH agonists may be maintained on these agents.
  • The subject is unable to swallow tablets
  • Individuals who are known to be HIV-positive are excluded from this study. HIV positive individuals are at increased risk of lethal infection when treated with marrow-suppressive agents, and cabozantinib has not adequately been tested in this population. Also, antiretroviral therapy may have pharmacokinetic interactions with cabozantinib that have not been fully characterized yet.
  • Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with cabozatinib, breastfeeding should be discontinued if the mother is treated with cabozantnib. These potential risks may also apply to other agents used in this study.
  • Subjects may not be receiving any other study agents concurrently while on this study

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Study of Cabozantinib (XL-184) Monotherapy in Patients With Advanced Cholangiocarcinoma After Progression on First or Second Line Systemic Therapy

This research study is evaluating a drug called cabozantinib as a possible treatment cancer of the bile duct. Cabozantinib is a drug that targets specific pathways inside the cells of the body. By blocking the c-MET and VEGFR2 pathways from sending signals, cabozantinib may prevent cells from multiplying. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to stop the growth of bile duct cancer.

In this research study, the investigators are looking to see how well cabozantinib works in slowing the growth of bile duct cancer. The investigators are also assessing the safety and tolerability of cabozantinib in participants with this type of cancer.

Read the detailed description

After the screening procedures confirm that the participants are eligible to participate in the research study:

A two-stage design will be employed in this study where at least 9 of the 20 patients enrolled in the first stage need to be progression-free at 16 weeks before the second stage can proceed. If this criterion is met, an additional 24 patients will be enrolled in the second stage for a total of 44 patients in the study. Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

In this research study, the participant will be given a study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be taking the study drug, cabozantinib daily. The diary will also include special instructions for taking the study drug(s).

The participant will continue to take cabozantinib for as long as it is tolerated without any unacceptable side effects and the cancer does not get worse.

The following tests and procedures will be done during the research study:

Cycle 1 - On days 1, 8 and 15

  • Medical History
  • Physical Exam including vital signs and height and weight
  • Performance Status
  • Review of side effects (day 8 and 15 only)
  • Routine blood tests (day 8 and 15 only)
  • TSH blood sample on day 1 only

Additional research procedures during Cycle 1:

  • Biomarker blood sample (about 2 teaspoons of blood) on day 3 and day 14

Cycles 2-3 - On days 1 and 15

  • Medical History
  • Physical Exam including vital signs, height and weight
  • Performance Status
  • Review of side effects
  • EKG - day 1 of each cycle ONLY
  • Routine blood tests
  • Urine test on Day 1 of each cycle ONLY
  • Urine pregnancy test on day 1 of each cycle for women of childbearing potential
  • TSH blood sample on day 1 only

Cycle 4 and Beyond: Day 1 ONLY

  • Medical History
  • Physical Exam including vital signs, height and weight
  • Performance Status
  • Review of side effects
  • EKG
  • Routine blood tests
  • TSH blood sample on day 1 only
  • Urine test
  • Urine pregnancy test for women of childbearing potential

The following tests will be done every 2 cycles during the research study:

  • CA 19-9 blood sample
  • Tumor measurements
  • Chest/Abdominal/Pelvic CT/MRI of your tumor

Planned Follow-up:

The participant will return to the clinic between 30-37 days after the last dose of cabozantinib for the following tests and procedures:

  • Medical History
  • Physical Exam including vital signs, height and weight
  • Performance Status
  • Review of side effects
  • Routine blood tests
  • CA 19-9 blood sample
  • TSH blood sample
Being tested
Cabozantinib
Keywords
Bile Duct Cancer, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, Cabozantinib
Medical subject headings
Bile Duct Neoplasms, Cholangiocarcinoma

What participants receive

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

  • CabozantinibDrug

    Also called XL-184

    Cabozantinib 60 mg (free base weight) per day will be administered daily and continuously for a cycle length of 28 days. Subjects will be provided with a sufficient supply of study treatment and instructions for taking the study treatment on days without scheduled clinic visits. After fasting (with exception of water) for 2 hours, subjects will take study treatment daily with a full glass of water (minimum of 8 oz/ 240 mL) and continue to fast for 1 hour after each dose of study treatment.

Study groups in NCT01954745
Study groupRoleWhat they receive
CabozantinibExperimentalPatients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.
Receives: Drug: Cabozantinib

What is being measured

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

  1. Median Progression Free Survival (PFS)

    To evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies.

    Measured: 2 Years

Secondary outcomes (3)

  1. Number of Patients With Adverse Events

    Evaluate the number of patients with advanced cholangiocarcinoma being treated with cabozantinib who have adverse events during treatment

    Measured: 2 Years

  2. Objective Response Rate (ORR)

    To evaluate the objective response rate (ORR) for patients with advanced cholangiocarcinoma receiving cabozantinib

    Measured: 2 Years

  3. Median Overall Survival (OS)

    To evaluate the median overall survival (OS) for patients with advanced cholangiocarcinoma receiving cabozantinib

    Measured: 2 years

Timeline

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

  1. First posted7 Oct 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionJun 2015
  4. Study completionJun 2016

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01954745
Sponsor's protocol ID
13-221
Other IDs
XL184-IST26
Status last verified
Dec 2016
First submitted
24 Sep 2013
Last updated
3 Feb 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Goyal L, Zheng H, Yurgelun MB, Abrams TA, Allen JN, Cleary JM, Knowles M, Regan E, Reardon A, Khachatryan A, Jain RK, Nardi V, Borger DR, Duda DG, Zhu AX. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma. Cancer. 2017 Jun 1;123(11):1979-1988. doi: 10.1002/cncr.30571. Epub 2017 Feb 13.

    PubMed 28192597

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Bile Duct Cancer and Intrahepatic Cholangiocarcinoma, run by Massachusetts General Hospital at 3 sites in United States.

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 22 inclusion and 60 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 3 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 3 Feb 2017). 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?

Median Progression Free Survival (PFS) (time frame: 2 Years). 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 NCT01954745, 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 3 Feb 2017.

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