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

Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02947152
• Other study ID #: CHKT288X2101
• Status: Terminated
• Phase: Phase 1
• Start date: December 1, 2016
• Est. completion date: September 14, 2017

Study information

• Verified date: September 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: September 14, 2017
• Est. primary completion date: September 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Carcinoma, Renal Cell
• Epithelial Ovarian Cancer
• Ovarian Neoplasms
• Renal Cell Carcinoma

Intervention

Drug:
• HKT288
Cadherin-6-targeting antibody-drug conjugate for intravenous administration

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Belgium	Novartis Investigative Site	Leuven
Japan	Novartis Investigative Site	Nagoya	Aichi
Spain	Novartis Investigative Site	Barcelona	Catalunya
Switzerland	Novartis Investigative Site	Locarno
United States	Novartis Investigative Site	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Japan,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period		evaluation period is 21 days
Primary	Safety assessed by overall incidence of adverse events (AEs) and serious adverse events (SAEs)		Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
Primary	Tolerability as assessed by numbers of dose changes or interruptions		Until last dose of study treatment (=average of approximately 6 months after first dose)
Primary	Safety assessed by severity of adverse events (AEs) and serious adverse events (SAEs)		Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
Secondary	Concentration vs. time profiles of total antibody (tAb)		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
Secondary	Objective response rate		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)
Secondary	Duration of response		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)
Secondary	Progression-free survival		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)
Secondary	Disease Control Rate		At 6 months on treatment
Secondary	Best overall response		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)
Secondary	Presence of anti-HKT288 antibodies.		On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
Secondary	CDH6 expression level		3 months
Secondary	Pharmacokinetics (PK) parameter (AUC) for HKT288		On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
Secondary	PK parameter (Cmax) for HKT288		On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
Secondary	PK parameter (Tmax) for HKT288		On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
Secondary	PK parameters (half-life) for HKT288		On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)

External Links

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