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Trial record 1 of 1 for:    NCT03498521
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A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site (CUPISCO)

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ClinicalTrials.gov Identifier: NCT03498521
Recruitment Status : Recruiting
First Posted : April 13, 2018
Last Update Posted : September 14, 2022
Sponsor:
Collaborator:
Foundation Medicine, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE April 5, 2018
First Posted Date  ICMJE April 13, 2018
Last Update Posted Date September 14, 2022
Actual Study Start Date  ICMJE July 10, 2018
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
Progression Free Survival (PFS1) [ Time Frame: From randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 60 months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
Progression Free Survival (PFS1) [ Time Frame: Randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 48 months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2021)
  • Overall Survival (OS) [ Time Frame: From randomization to death from any cause, through the end of study (approximately 60 months) ]
  • Objective Response Rate (ORR1) [ Time Frame: Two consecutive occurrences of complete or partial response >/=4 weeks apart ]
  • Duration of Response (DOR1) [ Time Frame: From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 60 months) ]
  • Disease Control Rate (DCR1) [ Time Frame: From randomization to death from any cause, through the end of study (approximately 60 months) ]
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: From baseline through the end of study (approximately 60 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • Overall Survival (OS) [ Time Frame: Randomization to death from any cause, through the end of study (approximately 48 months) ]
  • Overall Response Rate (ORR1) [ Time Frame: Two consecutive occurrences of complete or partial response >/=4 weeks apart ]
  • Duration of Clinical Benefit (DCB1) [ Time Frame: From the first occurrence of a complete response (CR), partial response (PR), or stable disease (SD) after randomization, until disease progression or death from any cause, through the end of study (approximately 48 months) ]
  • Percentage of Participants with Adverse Events (AE) [ Time Frame: From baseline through the end of study (approximately 48 months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site
Official Title  ICMJE A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy
Brief Summary This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer of Unknown Primary Site
Intervention  ICMJE
  • Drug: Alectinib
    Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Vismodegib
    Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Ipatasertib
    Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Olaparib
    Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Erlotinib
    Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Bevacizumab
    Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Vemurafenib
    Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Cobimetinib
    Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Trastuzumab Subcutaneous (SC)
    Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Pertuzumab
    Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)
  • Drug: Atezolizumab
    Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Carboplatin
    Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.
  • Drug: Paclitaxel
    Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC
  • Drug: Cisplatin
    Cisplatin will be administered intravenously, 60-75 mg/m^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.
  • Drug: Gemcitabine
    Gemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.
  • Drug: Entrectinib
    Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).
  • Drug: Ivosidenib
    Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
  • Drug: Pemigatinib
    Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Study Arms  ICMJE
  • Experimental: Molecularly-Guided Therapy
    Participants will be assigned to molecularly-guided therapy based on genomic profile.
    Interventions:
    • Drug: Alectinib
    • Drug: Vismodegib
    • Drug: Ipatasertib
    • Drug: Olaparib
    • Drug: Erlotinib
    • Drug: Bevacizumab
    • Drug: Vemurafenib
    • Drug: Cobimetinib
    • Drug: Trastuzumab Subcutaneous (SC)
    • Drug: Pertuzumab
    • Drug: Atezolizumab
    • Drug: Paclitaxel
    • Drug: Entrectinib
    • Drug: Ivosidenib
    • Drug: Pemigatinib
  • Active Comparator: Platinum-Based Chemotherapy
    Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
    Interventions:
    • Drug: Trastuzumab Subcutaneous (SC)
    • Drug: Pertuzumab
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Drug: Cisplatin
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2018)
790
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 31, 2024
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosed according to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP
  • No prior lines of systemic therapy for the treatment of CUP
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Candidate for platinum-based chemotherapy (according to the reference information for the intended chemotherapy)
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
  • Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample </= 4 months old that is expected to be sufficient for generation of a comprehensive genomic profile at a central reference pathology laboratory

Exclusion Criteria:

  • Squamous cell CUP
  • Participants who can be assigned to a specific subset of CUP for which a specific treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or with a clinical and IHC profile indicative of a specific primary tumor (favorable prognosis CUP subsets): Poorly differentiated carcinoma with midline distribution; women with papillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes; poorly differentiated neuroendocrine tumors; men with blastic bone metastases and elevated prostate-specific antigen (PSA); participants with a single, small, potentially resectable tumor; colon cancer-type CUP, including participants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive, CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHC profile indicative of breast cancer and either a history of breast cancer or lymph nodes in the drainage areas of the breast; high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor mass or lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniak classification higher than IIF; IHC profile compatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with only pulmonary metastases and/or lymph nodes in the drainage areas of the liver
  • Known presence of brain or spinal cord metastasis (including metastases that have been irradiated only)
  • Histology and immunohistology profiles (per 2015 ESMO guidelines) that are not adenocarcinoma or poorly differentiated carcinoma/adenocarcinoma
  • History or known presence of leptomeningeal disease
  • Known human immunodeficiency virus (HIV) infection
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 7 months after the final dose of treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: MX39795 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Bulgaria,   Chile,   Colombia,   Croatia,   Cyprus,   Czechia,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Kazakhstan,   Korea, Republic of,   Latvia,   Mexico,   Netherlands,   Norway,   Peru,   Poland,   Portugal,   Romania,   Spain,   Switzerland,   Thailand,   Turkey,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03498521
Other Study ID Numbers  ICMJE MX39795
2017-003040-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Foundation Medicine, Inc.
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP