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The Safety and Pharmacokinetics of IMP4297 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03507543
Recruitment Status : Recruiting
First Posted : April 25, 2018
Last Update Posted : April 25, 2018
Sponsor:
Information provided by (Responsible Party):
Impact Therapeutics, Inc.

Brief Summary:
This is a phase 1, First-In-Human, open label study, trialing a new PARP (poly-ADP ribose polymerase) inhibitor medication IMP4297 in participants with advanced solid tumour.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Breast Cancer Ovarian Cancer Prostate Cancer Primary Peritoneal Cancer Drug: IMP4297 Phase 1

Detailed Description:

This is a phase 1, First-In-Human, open label study, trialing a new PARP inhibitor medication IMP4297 in participants with advanced solid tumour.

Six different dosage cohorts 2mg, 6mg, 10mg, 20mg, 30mg and 40mg will be used to establish the maximum tolerated dosage. First participant in each dosing cohort will be administered one dose of IMP4297 capsule, followed by a wash out period of at least 5 half-lives or 7 days. Safety information such as pathology result or adverse events experienced will be collected following first dosing. This will be reviewed by the a safety review committee that is made up of the Principal Investigator, Medical Monitor, the study Sponsor and a representative from the Clinical Research Organisation, which will collectively determine if it is safe to proceed to continue with the next scheduled dosing cohort. Participant will proceed with repeat once daily dose at the same dose level for 3 weeks. Each repeat dose treatment cycle will be composed of 3 weeks (Day 1 to Day 21). IMP4297 will be administered by participants at home. Participants will be instructed to bring unused IMP4297 capsules with them to each visit for trial staff to review and confirm amount of IMP4297capsules taken since the last visit. The administration of the IMP4297 capsules will be recorded. Study drug compliance will be assessed using these records in conjunction with a count of unused IMP4297 capsules. Participants who are benefiting from IMP4297 may have the possibility of treatment beyond 1 year at the investigator's discretion. Participants who experience disease progression or unacceptable side effects, are not compliant with study protocol or in the opinion of the investigator will have IMP4297 administration discontinued and study participation will be terminated.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of IMP4297 in Patients With Advanced Solid Tumors
Actual Study Start Date : February 3, 2017
Estimated Primary Completion Date : July 31, 2018
Estimated Study Completion Date : December 31, 2018


Arm Intervention/treatment
Experimental: IMP4297 Drug: IMP4297
The dose levels will be escalated following a modified 3+3 dose escalation scheme.




Primary Outcome Measures :
  1. The AEs (adverse event) of single and multiple doses of IMP4297 administered to participants with advanced solid tumors. [ Time Frame: Each visit after IMP4297 administrated (through study completion, an average of 10 months) ]
    Evaluate the TEAE (treatment-emergent adverse event) of IMP4297

  2. The maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLTs) of IMP4297. [ Time Frame: Within 28 days after IMP4297 administrated ]
    Evaluate DLT and determine the MTD


Secondary Outcome Measures :
  1. Area Under Curve [AUClast, AUCINF and AUCtau] [ Time Frame: Within 7 days after firstly single dose administrated ]
  2. Area Under Curve [AUClast, AUCINF and AUCtau] [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]
  3. Maximum plasma concentration (Cmax) [ Time Frame: Within 7 days after firstly single dose administrated ]
  4. Maximum plasma concentration (Cmax) [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]
  5. Time at which Cmax occurred (Tmax) [ Time Frame: Within 7 days after firstly single dose administrated ]
  6. Time at which Cmax occurred (Tmax) [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]
  7. Trough Concentrations (Ctrough) [ Time Frame: Within 7 days after firstly single dose administrated ]
  8. Trough Concentrations (Ctrough) [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]
  9. Clearance (CL/F) [ Time Frame: Within 7 days after firstly single dose administrated ]
  10. Clearance (CL/F) [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]
  11. Volume of distribution (Vd/F) [ Time Frame: Within 7 days after firstly single dose administrated ]
  12. Volume of distribution (Vd/F) [ Time Frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle) ]


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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

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age greater than or equal to 18 years
  3. Histologically or cytologically documented, incurable, advanced solid malignancy that has progressed on, or failed to respond to, at least one prior systemic therapy
  4. Evaluable or measurable disease per RECIST 1.1
  5. ECOG performance status of 0 or 1
  6. In the dose expansion stage, patients with BRCA (breast carcinoma) mutation will be enrolled. Patients with breast cancer, ovarian cancer and prostate cancer are preferred.

Exclusion Criteria:

  1. Inadequate haematologic and organ function, defined by the following (haematologic parameters must be assessed greater than or equal to 14 days after a prior treatment, if any):

    1. Absolute neutrophil count <1500 cells/uL
    2. Haemoglobin <9 g/dL
    3. Total bilirubin >1.5 x the ULN, with documented liver metastases total bilirubin >3 x the ULN .
    4. AST and/or ALT >2.5 x the ULN, with documented liver metastases AST and/or ALT levels > 5 x the ULN.
    5. Serum creatinine > 1.5 x the ULN, or creatinine clearance < 50 mL/min based on a documented 24-hour urine collection.
    6. International normalized ratio (INR) > 1.5 x the ULN or activated partial thromboplastin time (aPTT) >1.5 x the ULN The INR applies only to patients who do not receive therapeutic anti-coagulation.
  2. Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy within 4 weeks prior to initiation of study treatment with the following exceptions:

    1. Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer
    2. Hormone-replacement therapy or oral contraceptives
    3. Palliative radiation to bone metastases > 2 weeks prior to Day 1
  3. Adverse events from prior anti-cancer therapy that have not resolved to CTCAE Grade less than or equal to 1, except for alopecia
  4. Clinical significant active infection
  5. Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  6. Known human immunodeficiency virus infection
  7. New York Heart Association (NYHA) Class II or greater congestive heart failure; history of myocardial infarction or unstable angina within 6 months prior to Day 1; history of stroke or transient ischemic attack within 6 months prior to Day 1
  8. Active or untreated brain metastasis
  9. Pregnant (positive pregnancy test) or lactating women
  10. Male or female patients of child-producing potential unwilling to use double barrier contraception: condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral, injectable or parenteral), implanon, or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
  11. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
  12. Inability to comply with study and follow-up procedures
  13. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

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): NCT03507543


Contacts
Contact: Pavina Pavina + 61 2 8437 9249 Pavina.Pavina@INCResearch.com

Locations
Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Bo Gao, Doctor    +61 2 9845 5200    bo.gao@sydney.edu.au   
St George Private Hospital Recruiting
Kogarah, New South Wales, Australia
Contact: Paul De Souza, Prof    +61295539588    p.desouza@unsw.edu.au   
Australia, Victoria
Nucleus Network Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Jason Lickliter, Docter       j.lickliter@nucleusnetwork.com.au   
Sponsors and Collaborators
Impact Therapeutics, Inc.
Investigators
Principal Investigator: Jason Lickliter Epworth Medical Centre
Principal Investigator: Paul Souza St George Private Hospital

Responsible Party: Impact Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03507543     History of Changes
Other Study ID Numbers: IMP4297-2016-AU01
First Posted: April 25, 2018    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Impact Therapeutics, Inc.:
Breast Cancer
Ovarian Cancer
Prostate Cancer
Advanced solid tumours
primary peritoneal Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Ovarian Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders