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

NCT01639508 | Recruiting Phase 2

• 1 other identifier: 12-097
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 7

Brief 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. 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. 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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung; XL184 (CABOZANTINIB); KIF5B/RET Positive; RET Fusion Positive; 12-097; Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

Outcome Measures

Primary Outcomes (2)

• 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

  12 weeks

• 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.

  12 weeks

Secondary Outcomes (5)

• progression-free survival (PFS) (Group A)

  3 years

• overall survival (OS) (Group A)

  3 years

• safety (Group A, B, C & D)

  3 years

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

  3 years

• overall survival (OS) (Group B, C & D)

  3 years

Other Outcomes (1)

• objective response rate (ORR) (Group D)

  12 weeks

Study Arms (1)

Cabozantinib

EXPERIMENTAL

This 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.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

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.

Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ii. NTRK fusion iii. MET overexpression, amplification, or mutation iv. AXL overexpression, amplification, or mutation
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Exelixis: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 27825636 DERIVED

• 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.

  PMID: 26291023 DERIVED

• 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.

  PMID: 23533264 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alexander Drilon, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Drilon, MD

CONTACT

646-888-4206

Mark Kris, MD

CONTACT

646-888-4197

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2012
• First Posted: July 12, 2012
• Study Start: July 1, 2012
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (7)