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

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ClinicalTrials.gov Identifier: NCT02947152
Recruitment Status : Terminated
First Posted : October 27, 2016
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Renal Cell Carcinoma Drug: HKT288 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 1, 2016
Actual Primary Completion Date : September 14, 2017
Actual Study Completion Date : September 14, 2017


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




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period [ Time Frame: evaluation period is 21 days ]
  2. 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) ]
  3. 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) ]
  4. 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 Measures :
  1. 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 ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. Disease Control Rate [ Time Frame: At 6 months on treatment ]
  6. 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) ]
  7. 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) ]
  8. CDH6 expression level [ Time Frame: 3 months ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02947152


Locations
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United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3000
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 466 8560
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site
Locarno, Switzerland, 6600
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02947152    
Other Study ID Numbers: CHKT288X2101
First Posted: October 27, 2016    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
HKT288
CDH6
ADC
maytansine
epithelial ovarian cancer
renal cell carcinoma
RCC
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases