Back to resultsA Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors (KAMELEON)
Primary Purpose
Bladder Cancer, Pancreas Cancer, Cholangiocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Trastuzumab Emtansine
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer
Eligibility Criteria
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
Sites / Locations
- IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
- Irccs Ospedale San Raffaele;Oncologia Medica
- Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
- IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
- A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
- Antoni van Leeuwenhoek Ziekenhuis
- Amsterdam UMC Location VUMC
- UMCG
- Erasmus MC - Centrum
- Narodny onkologicky ustav
- Complejo Hospitalario de Navarra
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital Duran i Reynals; Oncologia
- Hospital Ramon y Cajal; Servicio de Oncologia
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
- Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1 (UBC)
Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
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.
Secondary Outcome Measures
Progression-Free Survival (PFS)
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)
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)
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
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
Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02999672
Brief Title
A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors
Acronym
KAMELEON
Official Title
Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
December 23, 2016 (Actual)
Primary Completion Date
April 10, 2018 (Actual)
Study Completion Date
April 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Pancreas Cancer, Cholangiocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 (UBC)
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Trastuzumab Emtansine
Other Intervention Name(s)
Kadcyla
Intervention Description
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.
Primary Outcome Measure Information:
Title
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
Description
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.
Time Frame
Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
Title
Overall Survival (OS)
Description
OS was determined as the time from beginning of treatment to death from any cause.
Time Frame
Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
Title
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description
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).
Time Frame
Baseline up to approximately 18 months
Title
Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria
Description
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.
Time Frame
Baseline up to approximately 18 months
Title
Plasma/Serum Concentrations of Trastuzumab Emtansine
Description
Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
City
Meldola
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
Facility Name
Irccs Ospedale San Raffaele;Oncologia Medica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20141
Country
Italy
Facility Name
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
City
Verona
State/Province
Veneto
ZIP/Postal Code
37134
Country
Italy
Facility Name
Antoni van Leeuwenhoek Ziekenhuis
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Amsterdam UMC Location VUMC
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
UMCG
City
NL -groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Erasmus MC - Centrum
City
NL -rotterdam
ZIP/Postal Code
3000 CA
Country
Netherlands
Facility Name
Narodny onkologicky ustav
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Complejo Hospitalario de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Duran i Reynals; Oncologia
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Ramon y Cajal; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
City
Malaga
ZIP/Postal Code
29010
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors
We'll reach out to this number within 24 hrs