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Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02828098
Recruitment Status : Terminated
First Posted : July 11, 2016
Last Update Posted : July 31, 2020
Sponsor:
Collaborator:
Pivotal S.L.
Information provided by (Responsible Party):
Highlight Therapeutics

Brief Summary:

Part 1: 16 to 32 patients with aggressive solid tumors from whom biopsies can be obtained, will receive BO-112 through IT administration.

Injected lesions must be palpable and biopsiable at the time of injection, and biopsied after 7-14 days. Patients will not receive an alternative therapy during the period comprising from first and second biopsy. BO-112 will be administered at a starting dose. Upon confirmation of the safety profile of the starting dose and evaluation of the pharmacokinetic (PK) profile, three additional dose levels are expected to be tested.

During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability).

Additionally this study will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical relevance, will be studied.

Part 2: An additional 30 patients with progressive disease while on anti-PD1 treatment for an approved indication, will receive BO-112 through IT administration in combination with the anti-PD1 treatment to evaluate the safety and tolerability of the combination.

Injected lesions must be palpable and biopsiable at the time of injection. Patients will continue with their anti-PD1 treatment. During the course of the study, patients will be examined for any side effects that may occur (safety and tolerability).

Additionally this part of the trial will also study BO-112 biological activity, the innate and adaptive immune system response and signaling pathways, as well as signs of clinical response


Condition or disease Intervention/treatment Phase
Cancer Drug: Part 1: BO-112 Drug: Part 2: BO-112 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Exploratory First in Human Phase I Clinical and Pharmacokinetic Study of Intra-tumoral Administration of BO-112 in Adult Patients With Aggressive Solid Tumors, With an Extension Cohort in Combination With Anti-PD1 Treatment
Study Start Date : June 2016
Actual Primary Completion Date : July 2020
Actual Study Completion Date : July 2020

Arm Intervention/treatment
Experimental: Part 1: BO-112 IT
BO-112 dose 1 (starting dose) intratumoral injection. BO-112 dose 2, 3 and 4 are expected to be tested, upon confirmation of the safety profile of the starting dose.
Drug: Part 1: BO-112
Cohorts of three patients per dose level will be treated consecutively in the absence of Dose Limiting Toxicity (DLT).

Experimental: Part 2: BO-112 IT

Combination treatment of BO-112 intratumoral injections with standard of care nivolumab intravenous treatment

Or Combination treatment of BO-112 intratumoral injections with standard of care pembrolizumab intravenous treatment

Drug: Part 2: BO-112

BO-112 at a fixed dose will be administered as an intratumoral injection for up to 5 doses over 12 weeks and continue as long as there is benefit.

Nivolumab will be administered as an intravenous infusion every 2 weeks at a dose of 3 mg/kg for up to a total period of one year.

OR Pembrolizumab will be administered as an intravenous infusion every 3 weeks at either 200 mg or at 2 mg/kg depending on the indication, for up to a total period of one year.

Other Name: anti-PD1 monoclonal antibody




Primary Outcome Measures :
  1. Number of subjects with adverse events [ Time Frame: Part 1: Day 30 after administration of the last dose. Part 2: 12 weeks and for patients who continue up to 1 year ]
    To evaluate the safety and tolerability of B0-112 in terms of adverse events at every visit


Secondary Outcome Measures :
  1. Circulating cytokines including type I IFNs, TNFalpha and IL6 (by ELISA) [ Time Frame: Part 1: At three independent points during the study. Day 7-1 prior to administration, 24 hours after administration and 7-14 days after administration of the agent. Part 2: 12 weeks ]
  2. Plasma levels of BO-112 [ Time Frame: Part 1: 0-15-30-240 minutes and 24 hours after administration of the drug. Part 2: 1 day ]
    To characterize the pharmacokinetics (PK) of BO-112 by measuring the amount in plasma at regular timepoints during the study

  3. Anti-tumor activity [ Time Frame: 12 weeks and for patients who continue up to 1 year ]
    Part 2 only: To evaluate the antitumor activity of the combination of BO-112 and anti-PD1 treatment



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

Inclusion Criteria:

  1. Patients age 18 years or more on the day of signing informed consent form.
  2. Histologically or cytologically confirmed aggressive solid tumors
  3. Patients must have:

    • Biopsy-accessible tumors
    • No prior anticancer treatment during the last 14 days

Additional inclusion criteria for Part 2: disease progression on treatment with anti-PD1 antibody for an approved indication

Exclusion Criteria:

Other relevant and clinically significant concomitant diseases or adverse clinical conditions which may jeopardize patient safety:

  • Increased cardiac risk: congestive heart failure; or unstable angina pectoris; or arrhythmia requiring treatment or uncontrolled arterial hypertension; or myocardial infarction within 12 months before inclusion in the study.
  • Patients with active central nervous system (CNS) lesions (including carcinomatous meningitis) will be excluded. However, patients will be eligible if:

    • All known CNS lesions have been treated with stereotactic therapy or surgery, AND
    • There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 4 weeks after radiotherapy or surgery, and has not required to increase in the last 4 weeks their steroids use or has not started a new course of steroids
    • Whole brain radiotherapy is not allowed, with the exception of patients who have had definitive resection or stereotactic therapy of all radiologically detectable parenchymal brain lesions.
  • Active infection.
  • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis B or C).
  • Any clinically significant abnormality on history or examination including diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor).

Additional exclusion criteria for Part 2: Grade 3-4 toxicity due to anti-PD1 antibody or permanent discontinuation of anti-PD1 antibody due to immune related or other adverse reaction.


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): NCT02828098


Locations
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Spain
Clínica Universitaria Navarra
Pamplona, Navarra, Spain, 31008
ICO Hospital Duran i Reynals
Barcelona, Spain, 08908
Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario Quiron Madrid
Madrid, Spain, 28223
Hospital Universitario Virgen de la Victoria
Malaga, Spain, 29010
Sponsors and Collaborators
Highlight Therapeutics
Pivotal S.L.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Highlight Therapeutics
ClinicalTrials.gov Identifier: NCT02828098    
Other Study ID Numbers: 112/2016-IT
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Keywords provided by Highlight Therapeutics:
aggressive solid tumors
Additional relevant MeSH terms:
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Aggression
Behavioral Symptoms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs