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A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors (KAMELEON)

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ClinicalTrials.gov Identifier: NCT02999672
Recruitment Status : Completed
First Posted : December 21, 2016
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 19, 2016
First Posted Date  ICMJE December 21, 2016
Results First Submitted Date  ICMJE April 8, 2019
Results First Posted Date  ICMJE August 28, 2019
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE December 23, 2016
Actual Primary Completion Date April 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). [ Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months) ]
BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [<] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2016)
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) Criteria [ Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (assessed at baseline thereafter every 6 weeks up to 30 days after last infusion [infusion duration=90 mins] or 4-6 weeks after early discontinuation) (up to approximately 37 months overall) ]
Change History Complete list of historical versions of study NCT02999672 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months) ]
    PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
  • Overall Survival (OS) [ Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months) ]
    OS was determined as the time from beginning of treatment to death from any cause.
  • Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Baseline up to approximately 18 months ]
    Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).
  • Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria [ Time Frame: Baseline up to approximately 18 months ]
    Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.
  • Plasma/Serum Concentrations of Trastuzumab Emtansine [ Time Frame: Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days ]
    Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2016)
  • Progression-Free Survival Assessed by Investigator Using RECIST V1.1 Criteria [ Time Frame: Baseline up to PD or death, whichever occurs first (assessed at baseline thereafter every 6 weeks up to 30 days after last infusion [infusion duration=90 mins] or 4-6 weeks after early discontinuation) (up to approximately 37 months overall) ]
  • Overall Survival [ Time Frame: Baseline up to PD or death, whichever occurs first (assessed at baseline thereafter every 6 weeks up to 30 days after last infusion [infusion duration=90 mins] or 4-6 weeks after early discontinuation) (up to approximately 37 months overall) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 37 months ]
  • Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria [ Time Frame: Baseline up to approximately 37 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors
Official Title  ICMJE Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors
Brief Summary This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally advanced (unresectable and not treatable with curative intent) or metastatic urothelial bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no longer possible and where no other treatment options are available anymore. Participants will receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per kilogram [mg/kg], weekly [qw]) or Regimen B (3.6 mg/kg, every 3 weeks [q3w]) until unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever occurs first. Based on tolerability and safety aspects, steering committee and Independent Data Monitoring Committee (iDMC) will decide on expansion of the study to include more participants with other carcinoma types.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bladder Cancer
  • Pancreas Cancer
  • Cholangiocellular Carcinoma
Intervention  ICMJE Drug: Trastuzumab Emtansine
Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.
Other Name: Kadcyla
Study Arms  ICMJE
  • Experimental: Cohort 1 (UBC)
    First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC will initially receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
    Intervention: Drug: Trastuzumab Emtansine
  • Experimental: Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
    First six participants with metastatic pancreatic cancer/cholangiocarcinoma will receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
    Intervention: Drug: Trastuzumab Emtansine
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 Completed
Actual Enrollment  ICMJE
 (submitted: March 19, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2016)
76
Actual Study Completion Date  ICMJE April 10, 2018
Actual Primary Completion Date April 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ in greater than or equal to [>/=] 30 percent [%] of tumor cells): locally advanced (unresectable and not treatable with curative intent), or metastatic UBC or locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma
  • There must be no standard treatment options available for participants with the above HER2 overexpressing tumors and they must have undergone at least one prior platinum-based treatment for locally advanced (unresectable and not treatable with curative intent) or metastatic tumor (Note: for pancreatic cancer/cholangiocarcinoma, prior treatments are not required to be platinum-based.)
  • Participant's lesion should be measurable according to RECIST V1.1 on diagnostic computed tomography (CT) scan/magnetic resonance imaging (MRI); Target lesion(s) should not have been previously irradiated
  • At least one formalin-fixed paraffin-embedded (FFPE) biopsy of the primary tumor and/or from a metastatic site is required
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
  • No significant cardiac history and a current left ventricular ejection fraction (LVEF) >/=50%
  • Adequate organ function
  • Life expectancy of at least 12 weeks

Exclusion Criteria:

  • Participants with previous exposure to HER2-targeted therapies in any setting
  • Participants showing histologically confirmed focal HER2-expression, that is, less than (<) 30% of positively stained tumor cells
  • Participants with brain metastasis as the sole site of metastatic disease and/or are symptomatic or require therapy to control symptoms
  • Current uncontrolled hypertension (systolic greater than [>] 150 millimeters of mercury [mmHg] and/or diastolic >100 mmHg)
  • Current unstable angina pectoris
  • History of symptomatic congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria or ventricular arrhythmia that requires treatment
  • History of myocardial infarction within the last 6 months
  • Peripheral neuropathy, Grade >/=3
  • Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
  • Current severe, uncontrolled systemic disease
  • History of other malignancy within the last 5 years
  • Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C
  • Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the excipients of the investigational medicinal product (IMP)
  • Clinically significant bleeding within 30 days before enrollment
  • Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
  • Concurrent participation in any other therapeutic clinical trial
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Netherlands,   Slovakia,   Spain
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT02999672
Other Study ID Numbers  ICMJE MO29694
2015-001377-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2019

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