- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02947152
HKT288 in Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma
December 6, 2020 updated by: Novartis Pharmaceuticals
A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of HKT288, Administered Intravenously in Adult Patients With Advanced Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma
A first-in-human study using HKT288 in solid tumors, including epithelial ovarian cancer and renal cell carcinoma
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 1
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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Victoria
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Melbourne, Victoria, Australia, 3000
- Novartis Investigative Site
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Leuven, Belgium, 3000
- Novartis Investigative Site
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Aichi
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Nagoya, Aichi, Japan, 466 8560
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Locarno, Switzerland, 6600
- Novartis Investigative Site
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Texas
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Houston, Texas, United States, 77030
- Novartis Investigative Site
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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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Main Inclusion Criteria:
- Advanced (metastatic or locally advanced) serous epithelial ovarian, serous fallopian tubal or serous primary peritoneal cancer or advanced clear cell or papillary renal cell carcinoma who have received or are intolerant to all therapy known to confer clinical benefit for their disease, as determined by the investigator.
- Tumor sample is available for retrospective CDH6 expression testing
- Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
Main Exclusion Criteria:
- Patient has central nervous system metastatic involvement. Patients with previously treated CNS metastases are also excluded.
- Patient with any active or chronic corneal disorders
- Patients with monocular vision or have media opacities or any other condition that precludes monitoring of the retina or fundus.
- Patients with a history of serious allergic reactions
- Patients with QTcF >470 msec at screening ECG or congenital long QT syndrome
- Any prior history of treatment with maytansine (DM1 or DM4)-based ADC
Patient have received anti-cancer therapies within the following time frames prior to the first dose of study treatment:
- Conventional cytotoxic chemotherapy: ≤4 weeks (≤ 6 weeks for nitrosoureas and mitomycin-C)
- Biologic therapy (e.g., antibodies): ≤4 weeks
- Non-cytotoxic small molecule therapeutics: ≤5 half-lives or ≤2 weeks (whichever is longer)
- Other investigational agents: ≤4 weeks
- Radiation therapy (except for localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture): ≤4 weeks
- Radiation therapy (localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture) ≤2 weeks
- Major surgery: ≤2 weeks
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 |
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Experimental: Dose escalation part
Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma
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Cadherin-6-targeting antibody-drug conjugate for intravenous administration
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Experimental: Dose expansion part (RCC arm)
Includes patients with clear cell or papillary renal cell carcinoma
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Cadherin-6-targeting antibody-drug conjugate for intravenous administration
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Experimental: Dose expansion part (ovarian cancer arm)
Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)
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Cadherin-6-targeting antibody-drug conjugate for intravenous administration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period
Time Frame: evaluation period is 21 days
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evaluation period is 21 days
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Safety assessed by overall incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
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Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
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Tolerability as assessed by numbers of dose changes or interruptions
Time Frame: Until last dose of study treatment (=average of approximately 6 months after first dose)
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Until last dose of study treatment (=average of approximately 6 months after first dose)
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Safety assessed by severity of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
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Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Concentration vs. time profiles of total antibody (tAb)
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose). 1 cycle is 21 days, increases to 28 days if there is a dose delay of 7 days for the start of next dose
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose). 1 cycle is 21 days, increases to 28 days if there is a dose delay of 7 days for the start of next dose
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Objective response rate
Time Frame: every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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Duration of response
Time Frame: every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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Progression-free survival
Time Frame: every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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Disease Control Rate
Time Frame: At 6 months on treatment
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At 6 months on treatment
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Best overall response
Time Frame: every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months)
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Presence of anti-HKT288 antibodies.
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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CDH6 expression level
Time Frame: 3 months
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3 months
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Pharmacokinetics (PK) parameter (AUC) for HKT288
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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PK parameter (Cmax) for HKT288
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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PK parameter (Tmax) for HKT288
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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PK parameters (half-life) for HKT288
Time Frame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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 1, 2016
Primary Completion (Actual)
September 14, 2017
Study Completion (Actual)
September 14, 2017
Study Registration Dates
First Submitted
September 12, 2016
First Submitted That Met QC Criteria
October 25, 2016
First Posted (Estimate)
October 27, 2016
Study Record Updates
Last Update Posted (Actual)
December 8, 2020
Last Update Submitted That Met QC Criteria
December 6, 2020
Last Verified
September 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
Other Study ID Numbers
- CHKT288X2101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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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