A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6 (IT-01)
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|ClinicalTrials.gov Identifier: NCT03058289|
Recruitment Status : Recruiting
First Posted : February 20, 2017
Last Update Posted : November 21, 2018
|First Submitted Date ICMJE||February 10, 2017|
|First Posted Date ICMJE||February 20, 2017|
|Last Update Posted Date||November 21, 2018|
|Actual Study Start Date ICMJE||February 9, 2017|
|Estimated Primary Completion Date||July 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Rate and severity of treatment-emergent adverse events ≥ grade 3 attributed to study drug using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) [ Time Frame: Up to 3 years ]
The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease. All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03058289 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures
|Original Other Pre-specified Outcome Measures||Same as current|
|Brief Title ICMJE||A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6|
|Official Title ICMJE||A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers|
|Brief Summary||This study evaluates the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study is being conducted in patients with several types of refractory cancers including those at the surface of the skin (melanoma, head and neck, lymphoma, breast) and tumors within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also plans to test INT230-6 in combination with anti-PD-1 antibodies.|
INT230-6 is comprised of a 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumors and enables increased diffusion into cancer cells. (Nonclinical safety studies showed no findings following drug injection into healthy tissues.)
Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumors and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumor site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient.
Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents.
Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrates strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates.
Clinical trial IT-01 will thus seek to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus as part of study IT-01 the Sponsor will seek to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) receptors.
This study seek to understand whether tumor regression can be achieved and patient outcomes improved.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
There are up to 9 cohorts of subjects in the escalation portion of the protocol. The first is a superficial tumor cohort with a low tumor load (1:4 ratio of drug to tumor). The 2nd,3rd and 4th cohorts are in superficial and deep tumors that escalates the total dose and maximal dose per any one tumor. Cohort 5/6/7 will explore a higher drug load (1:2 ratio) and will escalate the total dose and maximal dose per any one tumor. The 8th cohort is reserved for combinations with anti-PD1 agent(s). The 9th optional cohort will be added if a more frequent schedule would be deemed beneficial. The specific regimens of the more frequent dosing regimen cohorts will be designated by the Study Steering Committee.Masking: None (Open Label)
There is no masking and all patients will receive INT230-6 treatments.Primary Purpose: Treatment
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||August 2020|
|Estimated Primary Completion Date||July 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
1. Men and Women > 18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status < 2;
2a. Eligibility: U.S. Sites
Includes subjects with loco-regional disease that have relapsed/recurred within 6 months of chemo-radiation and who have no standard of care.
Includes patients (subjects) with metastatic disease having injections into only superficial lesions that have failed (includes progression, relapse or intolerance) or not be a candidate for approved therapies. Note, patients (subjects) that have approved therapies available, which might confer clinical benefit, may be enrolled as long as the physician properly explains the nature of the treatment, and obtains consent ".
Includes patients (subjects) with metastatic disease having at least one deep tumor injection who have failed (includes progression, relapse or intolerance) all approved lines of therapy prior to enrollment unless they are not an appropriate candidate for a particular approved therapy or no approved therapy exists.
Note: There is no limit on the number of prior therapies that a patient (subject) may have received prior to enrollment in any cohort.
2b. Eligibility: Canadian Sites
Subjects with advanced or metastatic solid tumors that have disease progression after treatment with approved, available therapies (in site's country) for the cancer type or for whom available therapies have limited benefit and the subject refuses the available therapy. Includes subjects with locoregional disease that have relapsed/recurred within 6 months of chemo-radiation; or who have no standard of care or beneficial options. No limit on the number of prior treatments;
3. Subjects must have measurable disease by RECIST 1.1 criteria including one target tumor for injection. Superficial tumors must have one tumor greater than or equal to 1.0 cm, deep tumors greater than or equal to 1.0 cm (as measured by caliper (for non-injected tumors only) or image guidance);
4. Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors).
5. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer: systemic or IT) must have been completed at least 4 weeks prior to enrollment and all adverse events have either returned to baseline (or resolved to < grade 1); note: subjects who have received prior platinum therapy are eligible irrespective of their response.
6. Prior systemic radiation therapy (either IV, intrahepatic or oral) completed at least 4 weeks prior to study drug administration.
7. Prior focal radiotherapy completed at least 4 weeks prior to study drug administration.
8. Prior major treatment-related surgery completed at least 4 weeks prior to study drug administration;
9. No prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off steroid therapy for at least 2 months;
10a. Life expectancy ≥8 weeks all (US); 10b. Life expectancy ≥12 weeks; ≥ 8 weeks superficial tumors (Canada);
11. Subjects who may become pregnant or who are sexually active with a partner who could become pregnant are to use an effective form of barrier contraception during the study and for at least 60 days for female patients and 180 days for male patients after administration of study drug; and
12. Screening laboratory values must meet the following criteria:
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Canada, United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03058289|
|Other Study ID Numbers ICMJE||IT-01|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Intensity Therapeutics, Inc.|
|Study Sponsor ICMJE||Intensity Therapeutics, Inc.|
|PRS Account||Intensity Therapeutics, Inc.|
|Verification Date||July 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP