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

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 466 8560
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • Switzerland
      • Locarno, Switzerland, 6600
        • Novartis Investigative Site
  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Novartis Investigative Site

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
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
Drug: HKT288
Cadherin-6-targeting antibody-drug conjugate for intravenous administration
Experimental: Dose expansion part (RCC arm)
Includes patients with clear cell or papillary renal cell carcinoma
Drug: HKT288
Cadherin-6-targeting antibody-drug conjugate for intravenous administration
Experimental: Dose expansion part (ovarian cancer arm)
Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)
Drug: HKT288
Cadherin-6-targeting antibody-drug conjugate for intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period
Time Frame: evaluation period is 21 days
evaluation period is 21 days
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)
Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
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)
Until last dose of study treatment (=average of approximately 6 months after first dose)
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)
Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
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)
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)
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)
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)
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)
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)
Disease Control Rate
Time Frame: At 6 months on treatment
At 6 months on treatment
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)
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)
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)
On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
CDH6 expression level
Time Frame: 3 months
3 months
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)
On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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)
On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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)
On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
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)
On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

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.

Helpful Links

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

Keywords

Additional Relevant MeSH Terms

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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