Clinical trial NCT02947152: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Epithelial Ovarian Cancer
Renal Cell Carcinoma
Keywords: HKT288
CDH6
ADC
maytansine
epithelial ovarian cancer
renal cell carcinoma
RCC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-10-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period
timeFrame: evaluation period is 21 days
measure: Safety assessed by overall incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
measure: Tolerability as assessed by numbers of dose changes or interruptions
timeFrame: Until last dose of study treatment (=average of approximately 6 months after first dose)
measure: Safety assessed by severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose)
Secondary outcomes:
measure: Concentration vs. time profiles of total antibody (tAb)
timeFrame: 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
measure: Objective response rate
timeFrame: 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)
measure: Duration of response
timeFrame: 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)
measure: Progression-free survival
timeFrame: 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)
measure: Disease Control Rate
timeFrame: At 6 months on treatment
measure: Best overall response
timeFrame: 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)
measure: Presence of anti-HKT288 antibodies.
timeFrame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
measure: CDH6 expression level
timeFrame: 3 months
measure: Pharmacokinetics (PK) parameter (AUC) for HKT288
timeFrame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
measure: PK parameter (Cmax) for HKT288
timeFrame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
measure: PK parameter (Tmax) for HKT288
timeFrame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
measure: PK parameters (half-life) for HKT288
timeFrame: On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose)
Other outcomes:
Locations:
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Locarno
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: