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出境医 / 临床实验 / Outcomes of FoundationOne Directed Therapy in Cancer of Unknown Primary

Outcomes of FoundationOne Directed Therapy in Cancer of Unknown Primary

Study Description
Brief Summary:
The goal of the current study is to determine whether Foundation Medicine's next generation sequencing assay, called FoundationOne, will provide information that allows physicians to make treatment decisions using targeted therapies in clinical trials or FDA approved therapies, including "off-label" agents, that result in superior OS compared to historical outcomes for standard CUP therapy.

Condition or disease
Neoplasms, Unknown Primary CUP Metastatic Disease Poorly Differentiated Adenocarcinoma Poorly Differentiated Carcinoma Squamous Carcinoma Poorly Differentiated

Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 125 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Prospective Observational Trial Evaluating Outcomes of FoundationOne - Directed Matched Targeted Therapy in Patients With Cancer of Unknown Primary (CUP)
Study Start Date : May 2015
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017
Arms and Interventions
Group/Cohort
Class 1, 2, or 3 alterations, with targeted therapy
Patients put on targeted therapies matched to specific genomic alterations.
Site-specific therapy determined by tissue of origin testing
Patients put on therapy determined by tissue of origin testing (e.g., CancerTYPE ID)
Empiric CUP therapy
Patients put on empiric treatment at physician discretion
Outcome Measures
Primary Outcome Measures :
  1. Proportion of CUP patients who receive matched targeted therapy. [ Time Frame: Baseline visit ]

Secondary Outcome Measures :
  1. Overall survival (OS) in CUP patients receiving matched targeted therapy based on FoundationOne versus internal control CUP patients not receiving FoundationOne-directed therapy [ Time Frame: Every three months until death, [20 months] ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Newly diagnosed and previously treated patients with CUP.
Criteria

Inclusion Criteria:

  1. Patients with a histologically or cytologically confirmed diagnosis of metastatic or advanced unresectable cancer of unknown primary including adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, or squamous carcinoma.
  2. To be categorized as CUP, the following clinical evaluations must have been performed without identification of an anatomic primary site: medical history, physical examination, chemistry profile, blood counts, serum PSA (men), CT scans of chest/abdomen/pelvis, specific evaluation of symptomatic areas.
  3. Sufficient Formalin Fixed Paraffin Embedded tissue from cancer of study will allow previously completed profiling panels other than for treatment assignment; however, FoundationOne profiling is required as part of this study. Adequate tumor tissue must remain, in the estimate of the consenting physician, to confirm genomic alterations in enrolled patients. Previous unknown primary available for FoundationOne testing. (Note: This FoundationOne® profiling is also allowed and is not required to be FoundationOne repeated.) (see Appendix A and Appendix B)
  4. First and second line patients enrolling in this study must have an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2. Third line patients enrolling in this study must have an ECOG Performance Status score of 0 to 1 (Appendix C).
  5. Patients must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Appendix D).
  6. Age greater than or equal to 18 years.
  7. Patients are considered potential candidates for treatment with targeted therapy.
  8. Willingness and ability to comply with study and follow-up procedures.
  9. Ability to understand the nature of this study and give written informed consent.
  10. The presence of other active cancers is not allowed, unless indolent and not requiring therapy. Patients with early stage cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

Exclusion Criteria:

  1. Patients who have received three or more lines of systemic therapy for cancer of unknown primary.
  2. Patients who have previously received matched targeted therapy for the same Class 1 alteration (see Table 1) or the same drug.

  3. Patients with treatable CUP syndrome, including the following:

    • extragonadal germ cell syndrome
    • neuroendocrine carcinoma
    • adenocarcinoma isolated to axillary lymph nodes (women)
    • peritoneal carcinomatosis (women)
    • squamous cell carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes
    • single resectable metastasis
  4. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. Enzyme-inducing anticonvulsants are contraindicated.
  5. Pregnant or lactating.
  6. Psychological, familial, sociologic, or geographic conditions that do not permit compliance with the protocol.
Contacts and Locations

Locations
Layout table for location information
United States, Massachusetts
Foundation Medicine, Inc
Cambridge, Massachusetts, United States, 02141
Sponsors and Collaborators
Foundation Medicine
Rush University Medical Center
Stormont-Vail Healthcare
Jefferson Medical College of Thomas Jefferson University
The Cleveland Clinic
Sparrow Health System
Cancer & Hematology Centers of Western Michigan (CHCWM)
Allegheny Health Network
St. Luke's Hospital and Health Network, Pennsylvania
Solano Hematology Oncology
Horizon Oncology Center
Comprehensive Blood and Cancer Center
Lancaster Cancer Center
Western Maryland Health Center
Valley Medical Oncology
Cape Fear Valley Health System
Tri-County Hematology Oncology
Hematology & Oncology Associates
Broome Oncology
Orchard Healthcare
Ashland Bellefonte Cancer Center
Tennessee Cancer Specialists
North Shore Hematology Oncology
Good Samaritan
Zangmeister Cancer Center
Watson clinic
Oncology Consultants
Oncology Hematology Care
Northern Westchester Hospital
Peter MacCallum Cancer Center Trials Unit
Tracking Information
First Submitted Date December 1, 2015
First Posted Date December 11, 2015
Last Update Posted Date July 10, 2018
Study Start Date May 2015
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 10, 2015) 		Proportion of CUP patients who receive matched targeted therapy. [ Time Frame: Baseline visit ]
Original Primary Outcome Measures
 (submitted: December 9, 2015) 		Determine the proportion of CUP patients who receive matched targeted therapy. [ Time Frame: Baseline visit ]
Change History
Current Secondary Outcome Measures
 (submitted: December 10, 2015) 		Overall survival (OS) in CUP patients receiving matched targeted therapy based on FoundationOne versus internal control CUP patients not receiving FoundationOne-directed therapy [ Time Frame: Every three months until death, [20 months] ]
Original Secondary Outcome Measures
 (submitted: December 9, 2015) 		Compare overall survival (OS) in CUP patients receiving matched targeted therapy based on FoundationOne versus internal control CUP patients not receiving FoundationOne-directed therapy [ Time Frame: Every three months until death, [20 months] ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Outcomes of FoundationOne Directed Therapy in Cancer of Unknown Primary
Official Title A Prospective Observational Trial Evaluating Outcomes of FoundationOne - Directed Matched Targeted Therapy in Patients With Cancer of Unknown Primary (CUP)
Brief Summary The goal of the current study is to determine whether Foundation Medicine's next generation sequencing assay, called FoundationOne, will provide information that allows physicians to make treatment decisions using targeted therapies in clinical trials or FDA approved therapies, including "off-label" agents, that result in superior OS compared to historical outcomes for standard CUP therapy.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Newly diagnosed and previously treated patients with CUP.
Condition
  • Neoplasms, Unknown Primary
  • CUP
  • Metastatic Disease
  • Poorly Differentiated Adenocarcinoma
  • Poorly Differentiated Carcinoma
  • Squamous Carcinoma Poorly Differentiated
Intervention Not Provided
Study Groups/Cohorts
  • Class 1, 2, or 3 alterations, with targeted therapy
    Patients put on targeted therapies matched to specific genomic alterations.
  • Site-specific therapy determined by tissue of origin testing
    Patients put on therapy determined by tissue of origin testing (e.g., CancerTYPE ID)
  • Empiric CUP therapy
    Patients put on empiric treatment at physician discretion
Publications *
  • Drilon A, Wang L, Arcila ME, Balasubramanian S, Greenbowe JR, Ross JS, Stephens P, Lipson D, Miller VA, Kris MG, Ladanyi M, Rizvi NA. Broad, Hybrid Capture-Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches. Clin Cancer Res. 2015 Aug 15;21(16):3631-9. doi: 10.1158/1078-0432.CCR-14-2683. Epub 2015 Jan 7.
  • Ross JS, Cronin M. Whole cancer genome sequencing by next-generation methods. Am J Clin Pathol. 2011 Oct;136(4):527-39. doi: 10.1309/AJCPR1SVT1VHUGXW. Review.
  • Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P, Sun J, Juhn F, Brennan K, Iwanik K, Maillet A, Buell J, White E, Zhao M, Balasubramanian S, Terzic S, Richards T, Banning V, Garcia L, Mahoney K, Zwirko Z, Donahue A, Beltran H, Mosquera JM, Rubin MA, Dogan S, Hedvat CV, Berger MF, Pusztai L, Lechner M, Boshoff C, Jarosz M, Vietz C, Parker A, Miller VA, Ross JS, Curran J, Cronin MT, Stephens PJ, Lipson D, Yelensky R. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov;31(11):1023-31. doi: 10.1038/nbt.2696. Epub 2013 Oct 20.
  • Johnson DB, Dahlman KH, Knol J, Gilbert J, Puzanov I, Means-Powell J, Balko JM, Lovly CM, Murphy BA, Goff LW, Abramson VG, Crispens MA, Mayer IA, Berlin JD, Horn L, Keedy VL, Reddy NM, Arteaga CL, Sosman JA, Pao W. Enabling a genetically informed approach to cancer medicine: a retrospective evaluation of the impact of comprehensive tumor profiling using a targeted next-generation sequencing panel. Oncologist. 2014 Jun;19(6):616-22. doi: 10.1634/theoncologist.2014-0011. Epub 2014 May 5.
  • Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Luthra R, Ye Y, Wen S, Berry D, Kurzrock R. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res. 2012 Nov 15;18(22):6373-83. doi: 10.1158/1078-0432.CCR-12-1627. Epub 2012 Sep 10.
  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
  • Massard C, Loriot Y, Fizazi K. Carcinomas of an unknown primary origin--diagnosis and treatment. Nat Rev Clin Oncol. 2011 Nov 1;8(12):701-10. doi: 10.1038/nrclinonc.2011.158. Review.
  • Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012 Apr 14;379(9824):1428-35. doi: 10.1016/S0140-6736(11)61178-1. Epub 2012 Mar 12. Review.
  • Stella GM, Senetta R, Cassenti A, Ronco M, Cassoni P. Cancers of unknown primary origin: current perspectives and future therapeutic strategies. J Transl Med. 2012 Jan 24;10:12. doi: 10.1186/1479-5876-10-12. Review.
  • Gray SW, Hicks-Courant K, Cronin A, Rollins BJ, Weeks JC. Physicians' attitudes about multiplex tumor genomic testing. J Clin Oncol. 2014 May 1;32(13):1317-23. doi: 10.1200/JCO.2013.52.4298. Epub 2014 Mar 24.
  • Varadhachary GR, Raber MN. Carcinoma of unknown primary site. N Engl J Med. 2014 Nov 20;371(21):2040. doi: 10.1056/NEJMc1411384.
  • Petrakis D, Pentheroudakis G, Voulgaris E, Pavlidis N. Prognostication in cancer of unknown primary (CUP): development of a prognostic algorithm in 311 cases and review of the literature. Cancer Treat Rev. 2013 Nov;39(7):701-8. doi: 10.1016/j.ctrv.2013.03.001. Epub 2013 Apr 6. Review.
  • Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, Greco FA. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol. 2013 Jan 10;31(2):217-23. doi: 10.1200/JCO.2012.43.3755. Epub 2012 Oct 1.
  • Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 9, 2018) 		125
Original Estimated Enrollment
 (submitted: December 9, 2015) 		500
Actual Study Completion Date March 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Patients with a histologically or cytologically confirmed diagnosis of metastatic or advanced unresectable cancer of unknown primary including adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, or squamous carcinoma.
  2. To be categorized as CUP, the following clinical evaluations must have been performed without identification of an anatomic primary site: medical history, physical examination, chemistry profile, blood counts, serum PSA (men), CT scans of chest/abdomen/pelvis, specific evaluation of symptomatic areas.
  3. Sufficient Formalin Fixed Paraffin Embedded tissue from cancer of study will allow previously completed profiling panels other than for treatment assignment; however, FoundationOne profiling is required as part of this study. Adequate tumor tissue must remain, in the estimate of the consenting physician, to confirm genomic alterations in enrolled patients. Previous unknown primary available for FoundationOne testing. (Note: This FoundationOne® profiling is also allowed and is not required to be FoundationOne repeated.) (see Appendix A and Appendix B)
  4. First and second line patients enrolling in this study must have an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2. Third line patients enrolling in this study must have an ECOG Performance Status score of 0 to 1 (Appendix C).
  5. Patients must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Appendix D).
  6. Age greater than or equal to 18 years.
  7. Patients are considered potential candidates for treatment with targeted therapy.
  8. Willingness and ability to comply with study and follow-up procedures.
  9. Ability to understand the nature of this study and give written informed consent.
  10. The presence of other active cancers is not allowed, unless indolent and not requiring therapy. Patients with early stage cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

Exclusion Criteria:

  1. Patients who have received three or more lines of systemic therapy for cancer of unknown primary.
  2. Patients who have previously received matched targeted therapy for the same Class 1 alteration (see Table 1) or the same drug.

  3. Patients with treatable CUP syndrome, including the following:

    • extragonadal germ cell syndrome
    • neuroendocrine carcinoma
    • adenocarcinoma isolated to axillary lymph nodes (women)
    • peritoneal carcinomatosis (women)
    • squamous cell carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes
    • single resectable metastasis
  4. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. Enzyme-inducing anticonvulsants are contraindicated.
  5. Pregnant or lactating.
  6. Psychological, familial, sociologic, or geographic conditions that do not permit compliance with the protocol.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02628379
Other Study ID Numbers RAP-CLT-15-010
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Foundation Medicine
Study Sponsor Foundation Medicine
Collaborators
  • Rush University Medical Center
  • Stormont-Vail Healthcare
  • Jefferson Medical College of Thomas Jefferson University
  • The Cleveland Clinic
  • Sparrow Health System
  • Cancer & Hematology Centers of Western Michigan (CHCWM)
  • Allegheny Health Network
  • St. Luke's Hospital and Health Network, Pennsylvania
  • Solano Hematology Oncology
  • Horizon Oncology Center
  • Comprehensive Blood and Cancer Center
  • Lancaster Cancer Center
  • Western Maryland Health Center
  • Valley Medical Oncology
  • Cape Fear Valley Health System
  • Tri-County Hematology Oncology
  • Hematology & Oncology Associates
  • Broome Oncology
  • Orchard Healthcare
  • Ashland Bellefonte Cancer Center
  • Tennessee Cancer Specialists
  • North Shore Hematology Oncology
  • Good Samaritan
  • Zangmeister Cancer Center
  • Watson clinic
  • Oncology Consultants
  • Oncology Hematology Care
  • Northern Westchester Hospital
  • Peter MacCallum Cancer Center Trials Unit
Investigators Not Provided
PRS Account Foundation Medicine
Verification Date July 2018

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