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HKT288 in Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma

Primary Purpose

Epithelial Ovarian Cancer, Renal Cell Carcinoma

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

HKT288

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring HKT288, CDH6, ADC, maytansine, epithelial ovarian cancer, renal cell carcinoma, RCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose escalation part

Dose expansion part (RCC arm)

Dose expansion part (ovarian cancer arm)

Arm Description

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma

Includes patients with clear cell or papillary renal cell carcinoma

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period

Safety assessed by overall incidence of adverse events (AEs) and serious adverse events (SAEs)

Tolerability as assessed by numbers of dose changes or interruptions

Safety assessed by severity of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Concentration vs. time profiles of total antibody (tAb)

Objective response rate

Duration of response

Progression-free survival

Disease Control Rate

Best overall response

Presence of anti-HKT288 antibodies.

CDH6 expression level

Pharmacokinetics (PK) parameter (AUC) for HKT288

PK parameter (Cmax) for HKT288

PK parameter (Tmax) for HKT288

PK parameters (half-life) for HKT288

Full Information

NCT ID

NCT02947152

First Posted

September 12, 2016

Last Updated

December 6, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02947152

Brief Title

HKT288 in Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Terminated

Study Start Date

December 1, 2016 (Actual)

Primary Completion Date

September 14, 2017 (Actual)

Study Completion Date

September 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

A first-in-human study using HKT288 in solid tumors, including epithelial ovarian cancer and renal cell carcinoma

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epithelial Ovarian Cancer, Renal Cell Carcinoma

Keywords

HKT288, CDH6, ADC, maytansine, epithelial ovarian cancer, renal cell carcinoma, RCC

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose escalation part

Arm Type

Experimental

Arm Description

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma

Arm Title

Dose expansion part (RCC arm)

Arm Type

Experimental

Arm Description

Includes patients with clear cell or papillary renal cell carcinoma

Arm Title

Dose expansion part (ovarian cancer arm)

Arm Type

Experimental

Arm Description

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)

Intervention Type

Drug

Intervention Name(s)

HKT288

Intervention Description

Cadherin-6-targeting antibody-drug conjugate for intravenous administration

Primary Outcome Measure Information:

Title

Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period

Time Frame

evaluation period is 21 days

Title

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)

Title

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)

Title

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)

Secondary Outcome Measure Information:

Title

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

Title

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)

Title

Duration of response

Time Frame

Title

Progression-free survival

Time Frame

Title

Disease Control Rate

Time Frame

At 6 months on treatment

Title

Best overall response

Time Frame

Title

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)

Title

CDH6 expression level

Time Frame

3 months

Title

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)

Title

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)

Title

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)

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Novartis Investigative Site

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Novartis Investigative Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

466 8560

Country

Japan

Facility Name

Novartis Investigative Site

City

Barcelona

State/Province

Catalunya

ZIP/Postal Code

08035

Country

Spain

Facility Name

Novartis Investigative Site

City

Locarno

ZIP/Postal Code

6600

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17224

Description

Results for CHKT288X2101 can be found on the Novartis Clinical Trials Results Website

Learn more about this trial

HKT288 in Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma

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