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Non-Small Cell Lung CancerPhase 2NCT01639508

Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

A Phase 2 study testing Cabozantinib in people with Non-Small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
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
86 participants
Where
7 sitesUnited States
Study dates
Jul 2012to Jul 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • A subject must fully meet all of the following criteria to be eligible for the study:
  • The subject has a pathologic diagnosis of non-small cell lung carcinoma that is metastatic or unresectable.
  • Documented presence:
  • Group A: KIF5B/RET or related variant RET fusions.
  • Group B: any of the following aberrations
  • NTRK fusion iii. MET overexpression, amplification, or mutation iv. AXL overexpression, amplification, or mutation
Show all 26Show fewer
  • Group C: ROS1 fusion
  • GROUP D: RET-fusion post-progression on selective RET inhibitor
  • The subject is ≥ 18 years old on the day of consent.
  • Measurable Disease by RECIST1.1
  • The subject has a Karnofsky performance status of > 70%.
  • The subject has organ and marrow function and laboratory values as follows:
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 without colony stimulating factor support
  • Platelets ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 × the upper limit of normal (ULN). For subjects with known Gilbert's . disease, bilirubin ≤ 3.0 mg/dL
  • Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 30 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:
  • Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) Female:
  • Multiply above result by 0.85
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  • ≤ 3.0 × ULN if no liver involvement, or ≤ 5 × ULN with liver involvement
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (113.2 mg/mmol) creatinine or 24-hr urine protein of < 1 g
  • Serum phosphorus, magnesium, and potassium ≥ LLN after adequate supplementation if necessary
  • The subject is capable of understanding and complying with the protocol requirements and has signed the 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. 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

  • Any type of systemic anticancer agent (including investigational) within 3 weeks of first dose of study treatment, or within 5 half-lives of the agent whichever is shorter. Subjects on LHRH or GnRH agonists may be maintained on these agents.
  • Prior treatment with cabozantinib
  • Radiation therapy for bone or brain metastasis within 2 weeks, any other external radiation therapy within 4 weeks of first dose of study drug. Systemic treatment with radionuclides within 4weeks. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
  • Known uncontrolled symptomatic brain metastases or cranial epidural disease; subjects previously treated and on stable dose of corticosteroids and/or anticonvulsants for >10 days, or not requiring such medications, are eligible. Baseline brain scans are not required to confirm eligibility.
  • Radiation therapy for bone or brain metastases within 2 weeks before first dose of study drug; or any other external radiation therapy or systemic treatment with radionuclides within 4 weeks before first dose of study drug. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
Show all 47Show fewer
  • The subject requires concomitant treatment, in therapeutic doses, unless deemed clinically unsafe to discontinue, with anticoagulants such as warfarin or warfarin-related agents, unfractionated heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 100 mg/day), low-dose warfarin (≤ 1 mg/day) are permitted. Both prophylactic and/or treatment dose low molecular weight (fractionated) heparin (LMWH) are permitted and are the preferred agents to administer.
  • The subject has experienced any of the following within 3 months before the first dose of study treatment:
  • clinically-significant hematemesis or gastrointestinal bleeding
  • Clinically-significant hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood c. any other signs indicative of pulmonary hemorrhage
  • The subject has radiographic evidence of cavitating pulmonary lesion(s)
  • The subject has tumor in contact with invading major blood vessels
  • The subject has any evidence of an 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 BP ≥ 150 mm Hg systolic, or ≥ 90 mm Hg diastolic despite optimal antihypertensive treatment (Note: If there is any BP measurement that is performed within the screening period that is < 150 mm Hg systolic and <90 mm Hg diastolic, then BP does not meet definition of sustained.)
  • ---- Any congenital history of 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 except if anticoagulation is as stipulated in Exclusion Criterium #6. (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 treatmentF
  • intra-abdominal tumor/metastases invading GI mucosa (malignant abdominal ascites does not constitute mucosal invasion)
  • 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:
  • history of 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 ago. GI surgery (particularly when associated with delayed or incomplete healing) within 28 days. Note: Complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more that 28 days ago.
  • Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus.
  • 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
  • Major surgery (eg, thoracotomy, removal or biopsy of brain metastasis) within 3 months before Week 1 Day 1. Complete wound healing from major surgery must have occurred 1 month before Week 1 Day 1 and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before Week 1 Day 1. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • history of major surgery as follows:
  • The subject is unable to swallow tablets
  • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms 14 days before Week 1 Day 1
  • The subject is pregnant or breastfeeding.
  • The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  • Uncontrolled concurrent malignancy that would limit assessment of efficacy of cabozantinib.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Alexander Drilon, MD contact

646-888-4206

Jessica Ross, MD contact

646-608-4422

7 sites in 1 country

United States7 sites, 7 recruiting

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

    Alexander Drilon, MD, 646-888-4206

    Recruiting

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

    Alexander Drilon, MD, 646-888-4206

    Recruiting

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

    Alexander Drilon, MD, 646-888-4206

    Recruiting

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

    Alexander Drilon, MD, 646-888-4206

    Recruiting

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

    Alexander Drilon, MD, 646-888-4206

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Alexander Drilon, MD, 646-888-4206

    Jessica Ross, MD, 646-608-4422

    Recruiting

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

    Alexander Drilon, MD, 646-888-4188

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity.

A phase II study looks at how effective a medication is at treating a specific type of cancer and collects information on the side effects of the study treatment.

Read more

RET, ROS1, or NTRK fusion or increased MET or AXL activity gene leads to lung cancer cell growth. Cabozantinib is an oral medicine that inhibits of RET, ROS1, NTRK, MET, and AXL. In addition, this drug interferes with other cell pathways that also cause cancer cells to grow, form new blood vessels, and spread to other organs of the body. The goal of using cabozantinib is to shrink the cancer and to prevent it from growing

Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good idea of what side-effects it causes and can anticipate them.

Being tested
Cabozantinib
Keywords
Lung, XL184 (CABOZANTINIB), KIF5B/RET Positive, RET Fusion Positive, 12-097, Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • CabozantinibDrug

    Patients will receive cabozantinib at an initial dose of 60 mg orally daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. Dose modifications for drug toxicity are permitted as per a prescribed algorithm. During the Treatment Period subjects will receive cabozantinib until either disease progression, the occurrence of unacceptable drug-related toxicity or for other reason(s) for subject withdrawal.

Study groups in NCT01639508
Study groupRoleWhat they receive
CabozantinibExperimentalThis will be a single-institution, open label, two-stage, single agent trial of cabozantinib in patients with advanced NSCLCs.atients in GROUP A will have tumors with a RET fusion. Patients in GROUP B will have tumors with an NTRK fusion, or MET or AXL overexpression, amplication, or mutatation. Patients in GROUP C will have tumors with a ROS1 fusion. Patients in GROUP D will have tumors with a RET fusion and have progressed on a selective RET TKI.
Receives: Drug: Cabozantinib

What is being measured

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

  1. objective response rate (ORR) (Group A)

    by RECIST v1.1 criteria to cabozantinib in patients with advanced NSCLC who have tested positive for RET Fusion

    Measured: 12 weeks

  2. objective response rate (ORR) (Group B)

    by RECIST v1.1 criteria to cabozantinib in patients with advanced NSCLC whose tumors test positive for a ROS1 or NTRK fusion or MET or AXL overexpression, amplification, or mutation.

    Measured: 12 weeks

Secondary outcomes (5)

  1. progression-free survival (PFS) (Group A)

    Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up.

    Measured: 3 years

  2. overall survival (OS) (Group A)

    Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up.

    Measured: 3 years

  3. safety (Group A, B, C & D)

    Observed toxicities will be individually tabulated according to CTCAE version 4.0 and summarized using descriptive statistics.

    Measured: 3 years

  4. progression-free survival (PFS) (Group B, C & D)

    Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up with advanced NSCLCs whose tumors test positive for a ROS1 or NTRK fusion or MET or AXL overexpression or amplification who were treated with cabozantinib.

    Measured: 3 years

  5. overall survival (OS) (Group B, C & D)

    Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up with advanced NSCLCs whose tumors test positive for a ROS1 or NTRK fusion or MET or AXL overexpression or amplification who were treated with cabozantinib.

    Measured: 3 years

Timeline

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

  1. First posted12 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2027 (estimated)

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
86 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01639508
Sponsor's protocol ID
12-097
Status last verified
Oct 2026
First submitted
10 Jul 2012
Last updated
30 Oct 2026
Results posted
No

Publications

  • Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, Van Voorthuysen M, Somwar R, Smith RS, Montecalvo J, Plodkowski A, Ginsberg MS, Riely GJ, Rudin CM, Ladanyi M, Kris MG. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016 Dec;17(12):1653-1660. doi: 10.1016/S1470-2045(16)30562-9. Epub 2016 Nov 4.

    PubMed 27825636

  • Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.

    PubMed 26291023

  • Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens P, Ross J, Miller V, Ginsberg M, Zakowski MF, Kris MG, Ladanyi M, Rizvi N. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 2013 Jun;3(6):630-5. doi: 10.1158/2159-8290.CD-13-0035. Epub 2013 Mar 26.

    PubMed 23533264

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Non-Small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 7 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 26 inclusion and 47 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: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Alexander Drilon, MD (646-888-4206), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

objective response rate (ORR) (Group A) (time frame: 12 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 NCT01639508, which also lists 3 linked publications.

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 30 Oct 2026.

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