Patients who test positive for ROS1 cancer have several clinical trials options. The trials listed below either use a drug known to have activity against ROS1+ cancer, or specifically include ROS1+ cancer patients. Although ROS1+ cancer can begin in several different organs, many of these trials focus on non-small cell lung cancer (NSCLC) because most metastatic NSCLC patients are routinely tested for ROS1 in the US.

Three types of trials are listed:

  1. Treatment clinical trials” offer treatment options for ROS1+ cancer. Some of these trials have preclinical data or preliminary clinical trial data available (see Drugs To Treat ROS1+ Cancer). Check out the National Institutes of Health page about clinical trials to learn more about clinical trial phases, enrollment, and risks.
  2. Expanded access to experimental drugs” trials enable some patients to access a drug that has strong evidence of effectiveness for ROS1+ cancer, but does not yet have regulatory approval. Expanded access is sometimes called “compassionate use.” Each patient will need their oncologist to apply for access these trials.
  3. Biomarker clinical trials” may be looking for the incidence of certain driving mutations or proteins, or may be evaluating the accuracy of a new test that identifies cancer in a less invasive manner than tissue biopsies.

Choosing to participate in a study is an important personal decision. Talk with your doctor, family members or friends, and other patients involved in clinical trials about deciding to join a study. The sequence in which you try different drugs could make a difference in your treatment outcome–some drugs can treat resistance mutations that arise while taking other drugs, and some clinical trials limit the different ROS1+ targeted therapies you can take before enrolling. If your doctor is not familiar with ROS1+ treatments and clinical trials, it might be wise for your doctor (or you) to consult a ROS1 expert. You can also talk to other ROS1ders, as we have many clinical trial participants in the group.

Click on the study title to see the trial description on the National Institutes of Health’s clinicaltrials.gov website.  This description will provide more details about the study (study sponsor, phase, sites, detailed inclusion requirements, etc).

TREATMENT CLINICAL TRIALS

NCT02499614:  Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
Status: Recruiting (first posted 16-Jul-2015)
Eligible cancers: Non-Small-Cell Lung Carcinoma (NSCLC)
Interventions: crizotinib
Countries: Italy (27 sites)

NCT02650401: Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions
Status: Recruiting (First posted 8-Jan-2016)
Eligible cancers: solid tumors; CNS tumors; neuroblastoma
Interventions: entrectinib
Countries: USA (14 states)

NCT02568267: Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
Status: Recruiting (posted 5-Oct-2015)
Eligible cancers: Breast Cancer; Cholangiocarcinoma; Colorectal Cancer; Head and Neck Neoplasms; Large-Cell Anaplastic Lymphoma; Melanoma; Neuroendocrine Tumors; Non-small Cell Lung Cancer (NSCLC); Ovarian Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Primary Brain Tumors; Renal Cell Carcinoma; Sarcomas; Salivary Gland Cancers; Adult Solid Tumor
Interventions: entrectinib
Countries:  USA (all states), Australia, Belgium, France, Germany, Hong Kong, Italy, Japan, Republic of Korea, Netherlands, Poland, Singapore, Spain, Taiwan, United Kingdom
Note: Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements). Prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression–contact Ignyta in this situation.

NCT02097810: Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations
Status: Recruiting (first posted 27-Mar-2014)
Eligible cancers: locally advanced solid tumors; metastatic solid tumors
Interventions: entrectinib
Countries: several

NCT01970865: A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations
Status: Active, not recruiting (study started Oct-2013)
Eligible cancers: ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC
Interventions: PF-06463922 (lorlatinib) and crizotinib
Countries: USA (11 states), Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Republic of Korea, Singapore, Spain, Switzerland, Taiwan

NCT01639508: 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
Status: Recruiting (study started Jul-2012)
Eligible cancers
: Non-small Cell Lung Cancer (NSCLC)
Interventions: cabozantinib
Countries: USA (2 states)

NCT02638909: Study of Oral Ceritinib in Patients With ALK and ROS1 Activated Gastrointestinal Malignancies
Status: Recruiting (study started Dec-2015)
Eligible cancers
: Colorectal Adenocarcinoma; Cholangiocarcinoma; Pancreatic Adenocarcinoma; Hepatocellular Adenocarcinoma; Gastric Adenocarcinoma; Esophageal Adenocarcinoma
Interventions: ceritinib
Countries: USA (6 states)

NCT02374489: A Phase II Trial of LDK378 in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma
Status: Recruiting
Eligible cancers: Cholangiocarcinoma
Interventions: LDK378 (certinib)
Countries: Taiwan

NCT02946359: A+C in Metastatic Lung Adenocarcinoma Cancer
Status: Recruiting
Eligible cancers: Metastatic Lung Adenocarcinoma
Interventions: crizotinib, bevacizumab
Countries: China

NCT02927340: A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions
Status: Recruiting
Eligible cancers: Non-small Cell Lung
Interventions: lorlatinib
Countries: USA (Massachusetts General Hospital, Boston, MA)

NCT03093116: A Study of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Status: Recruiting
Eligible cancers: Locally Advanced Solid Tumors; Metastatic Solid Tumors; Non Hodgkin Lymphoma
Interventions: Oral TPX-0005
Countries: USA (4 states)

NCT03088930: Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer
Status: Not yet recruiting
Eligible cancers: Non-small Cell Lung Cancer (NSCLC)
Interventions: crizotinib
Countries: USA (University of Colorado, Denver, CO)
Notes: This study is for ROS1+ NSCLC patients who have tumors that can be removed by surgery.

NCT01964157: An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement
Status: Recruiting
Eligible cancers: Non-small Cell Lung Cancer (NSCLC)
Interventions: LDK378 (ceritinib)
Countries: Republic of Korea

NCT 02279433: A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b
Status: Active, not recruiting
Eligible cancers: Solid tumors
Interventions: DS6051b
Countries: USA (4 states)

NCT02034981: Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1
Status: Recruiting
Eligible cancers: Hematologic Cancers; Solid Tumors; Metastatic Cancer
Interventions: crizotinib
Countries: France

NCT02314364: A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC
Status: Recruiting
Eligible cancers: Metastatic Non-small Cell Lung Cancer (NSCLC); Targetable Oncogenes (EGFR, ALK, ROS1)
Interventions: stereotactic body radiation therapy (SBRT) with protons or photons
Countries: USA (Massachusetts General Hospital, Boston, MA)

NCT03107988: Study of Lorlatinib (PF-06463922)
Status: Not yet recruiting
Eligible cancers: Neuroblastoma
Interventions: lorlatinib, cyclophosphamide, topotecan
Countries: USA (11 states), Canada, France, United Kingdom (UK)

NCT02223819: Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
Status: Recruiting
Eligible cancers: Uveal Melanoma
Interventions: crizotinib
Countries: USA (3 states)

NCT02846792: Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer
Status
: Recruiting
Eligible cancers: ALK Gene Translocation; EGFR Activating Mutation; ROS1 Gene Translocation; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIB Non-small Cell Lung Cancer (NSCLC); Stage IV Non-small Cell Lung Cancer (NSCLC)
Interventions: Laboratory Biomarker Analysis; Nivolumab (immunotherapy); Plinabuilin
Countries: USA (University of Washington/Fred Hutch Cancer Research Center, Seattle, WA)

NCT02267027: A Phase II, Open Label, Multiple Arm Study of AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer
Status: Recruiting
Eligible cancers: Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma
Interventions: ROS1+ patients receive LDK378 (ceritinib); patients with other types of cancer receive drugs that target their genomic type of cancer
Countries: China (Guangzhou, Guangdong)

NCT02693535: TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
Status: Recruiting
Eligible cancers: Non-Hodgkin Lymphoma; Multiple Myeloma; Advancd Solid Tumors
Interventions: ROS1+ patients receive crizotinib
Countries: USA (13 states)

NCT03049618: Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475
Status: Recruiting
Eligible cancers: ROS1 Gene Mutation; ALK Gene Mutation; BRAF Gene Mutation; EGFR Gene Mutation; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Non-small Cell Lung Cancer (NSCLC); Stage IIIA NSCLC; Stage IIIB NSCLC; Stage IV NSCLC
Interventions: Laboratory Biomarker Analysis; Pembrolizumab (immunotherapy); Recombinant EphB4-HSA Fusion Protein
Countries: USA (University of Southern California, Los Angeles, CA)

NCT02465060: NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma
Status: Recruiting
Eligible cancers: Advanced Malignant Solid Neoplasm; Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Plasma Cell Myeloma; Refractory Malignant Neoplasm; Refractory Plasma Cell Myeloma
Interventions: ROS1+ patients receive crizotinib
Countries: USA (50 states), Puerto Rico

NCT03155620: Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Advanced Refractory Solid Tumors or Lymphomas
Status: Not yet recruiting
Eligible cancers: Histiocytic Sarcoma; Juvenile Xanthogranuloma; Langerhans Cell Histiocytosis; Lymphoma; Recurrent Central Nervous System Neoplasm; Recurrent Malignant Solid Neoplasm; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm
Interventions: ROS1+ patients receive X-396 (ensartinib)
Countries: USA (Childrens Oncology Group, Philadelphia. PA)

NCT00585195: A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer
Status: Recruiting
Eligible cancers: ALK-positive Non-small Cell Lung Cancer (NSCLC); c-Met Dependent NSCLC; ROS Marker Positive NSCLC; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies (Except Leukemia)
Interventions: PF-02341066 (crizotinib), Rifampin, Itraconazole
Countries: USA (10 states), Australia, Republic of Korea
Notes: This is the original trial for crizotinib. It has been expanded over time to include new arms.

NCT02664935 National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer
Status: Not yet recruiting
Eligible cancers: Non-small Cell Lung Cancer (NSCLC); Squamous Cell Carcinoma; Adenocarcinoma
Interventions: ROS1+ patients receive crizotinib
Countries: United Kingdom (UK)

NCT03087448 Ceritinib + Trametinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC)
Status: Recruiting
Eligible cancers: Stage IIIb/IV ROS1+ (Phase 1 only) or ALK+ Non-small Cell Lung Cancer (NSCLC)
Interventions: Ceritinib + Trametinib
Countries: University of California at San Francisco

EXPANDED ACCESS TO EXPERIMENTAL DRUGS

NCT03066661: Expanded Access to Entrectinib for Cancers With NTRK1/2/3, ROS1, or ALK Gene Fusions
Status: Available
Eligible cancers: advanced cancer with an NTRK1, NTRK2, NTRK3, ROS1, or ALK gene fusion AND unable to participate in an ongoing entrectinib (RXDX-101) clinical trial
Interventions: entrectinib
Countries: Contact Ignyta at STARTRKtrials@ignyta.com or call +1-844-Startrk (782-7875)

NCT03178071: Expanded Access For Lorlatinib For Patients With Non Small Cell Lung Cancer Harboring Specific Molecular Alterations
Status: Available (posted 6-Jun-2017)
Eligible cancers: ALK+ and ROS1+ NSCLC
Interventions: lorlatinib
Countries: US states Arizona, Michigan, Washington (others in process)
Notes: Learn more about Pfizer’s compassionate use/extended access program

NCT 02473497: Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients
Status: Available
Eligible cancers: Neoplasm
Interventions: crizotinib
Countries: contact the drug manufacturer (Pfizer)

BIOMARKER CLINICAL TRIALS (no treatment)

NCT02946216: ALK/ROS1/MET Mutations on Plasma ctDNA in Patients With NSCLC
Status: Not yet recruiting
Eligible cancers
: Non-small Cell Lung Cancer (NSCLC) Stage III; Non-small Cell Lung Cancer (NSCLC) Metastatic; Adenocarcinoma of Lung; EGFR Wildtype
Interventions: Genetic analysis using circulating tumor DNA (no treatment)
Countries: China (Hangzhou, Zhejiang)

NCT03375437: Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions (RNASARC)
Status: Not yet recruiting (anticipated start date January 15, 2018)
Eligible cancers
: Advanced or metastatic soft tissue sarcomas
Interventions: molecular analysis of tumor samples for ALK, NTRK1/2/3, and ROS1
Countries: France (2 locations)
Notes: Patients who test positive for ALK, NTRK1/2/3, or ROS1 will be referred to entrectinib trial (STARTRK-2 NCT02568267)

Updated 29-Dec-2017