- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02999672
A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors (KAMELEON)
July 22, 2019 updated by: Hoffmann-La Roche
Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Emilia-Romagna
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Meldola, Emilia-Romagna, Italy, 47014
- IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
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Lombardia
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Milano, Lombardia, Italy, 20132
- Irccs Ospedale San Raffaele;Oncologia Medica
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Milano, Lombardia, Italy, 20141
- Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
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Veneto
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Padova, Veneto, Italy, 35128
- IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
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Verona, Veneto, Italy, 37134
- A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
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Amsterdam, Netherlands, 1066 CX
- Antoni van Leeuwenhoek Ziekenhuis
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Amsterdam, Netherlands, 1081 HV
- Amsterdam UMC Location VUMC
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NL -groningen, Netherlands, 9700 RB
- UMCG
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NL -rotterdam, Netherlands, 3000 CA
- Erasmus MC - Centrum
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Bratislava, Slovakia, 833 10
- Narodny onkologicky ustav
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Barcelona, Spain, 08035
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
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Barcelona, Spain, 08907
- Hospital Duran i Reynals; Oncologia
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Madrid, Spain, 28034
- Hospital Ramon y Cajal; Servicio de Oncologia
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Madrid, Spain, 28041
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
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Malaga, Spain, 29010
- Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
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Navarra
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Pamplona, Navarra, Spain, 31008
- Complejo Hospitalario de Navarra
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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).
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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 Names:
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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).
|
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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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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.
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Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS)
Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
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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.
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Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
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Overall Survival (OS)
Time Frame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
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OS was determined as the time from beginning of treatment to death from any cause.
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Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
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Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Time Frame: Baseline up to approximately 18 months
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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).
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Baseline up to approximately 18 months
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Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria
Time Frame: Baseline up to approximately 18 months
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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.
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Baseline up to approximately 18 months
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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
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Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.
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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
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 23, 2016
Primary Completion (Actual)
April 10, 2018
Study Completion (Actual)
April 10, 2018
Study Registration Dates
First Submitted
December 19, 2016
First Submitted That Met QC Criteria
December 19, 2016
First Posted (Estimate)
December 21, 2016
Study Record Updates
Last Update Posted (Actual)
August 28, 2019
Last Update Submitted That Met QC Criteria
July 22, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Pancreatic Neoplasms
- Cholangiocarcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Trastuzumab
- Maytansine
- Ado-Trastuzumab Emtansine
Other Study ID Numbers
- MO29694
- 2015-001377-40 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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