We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    INT230-6
Previous Study | Return to List | Next Study

A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6 (IT-01)

This study is currently recruiting participants.
Verified August 2017 by Intensity Therapeutics, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03058289
First Posted: February 20, 2017
Last Update Posted: November 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
University of Southern California
University Health Network, Toronto
Information provided by (Responsible Party):
Intensity Therapeutics, Inc.
  Purpose
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.

Condition Intervention Phase
Melanoma Head and Neck Cancer Lymphoma Breast Cancer Pancreatic Cancer Liver Cancer Colon Cancer Lung Cancer Glioblastoma Drug: INT230-6 Biological: anti-PD-1 Biological: anti-PD-1 antibody Phase 1 Phase 2

Study Type: Interventional
Study Design: 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.
Masking: None (Open Label)
Masking Description:
There is no masking and all patients will receive INT230-6 treatments.
Primary Purpose: Treatment
Official Title: A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers

Resource links provided by NLM:


Further study details as provided by Intensity Therapeutics, Inc.:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • Preliminary Efficacy: Control or Regression of Injected Tumors by Measurement of Length, Width and Height (in centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging to Calculate Tumor Volumes (cubic centimeters) Over Time. [ Time Frame: Up to 18 months ]
    Assess the preliminary efficacy of INT230-6 by measuring the length, width and height (centimeters) of injected tumor during the dosing and afterward.

  • Determine pharmacokinetic parameter Peak Plasma (Cmax in ng/mL) of each of the 3 main components of INT230-6. [ Time Frame: Up to 5 months ]
    Characterize the peak plasma profile for the three INT230-6 components after single and then multiple IT tumor site injections for safety purposes.

  • Determine key pharmacokinetic parameter, Area Under the Curve (AUC) (ng*hr/mL) of each of the 3 main components of INT230-6. [ Time Frame: Up to 5 months ]
    Characterize the pharmacokinetic AUC profile of each of the three INT230-6 components for AUC after single IT tumor site injection for safety purposes.

  • Key pharmacokinetic parameters, half live (hours) of each of the 3 main components of INT230-6. [ Time Frame: Up to 5 months. ]
    Characterize the half life of each of the three INT230-6 components after single and multiple IT tumor site injections for safety purposes.


Other Outcome Measures:
  • Exploratory: Control or Regression of Non Injected Tumors by Measurement of Length (in centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging. [ Time Frame: Up to 18 months ]
    Characterize response in non-injected lesions (up to 5) using length (cm) as the key parameter for measurement.

  • Exploratory: Blood, Genetic and Tissue Biomarker Identification from cell flow phenotyping, tissue analysis, genetic SNP analysis. [ Time Frame: Up to 2 months ]
    Evaluate various tumor and anti-tumor immune response biomarkers from blood, tumor tissue that may correlate with tumor response. Flow panels include Live-Dead, CD3, CD4, CD8, FoxP3, Ki-67, ICOS, PD-1, LAG-3, TIM-3, CTLA-4. and analysis of blood serum cytokine such as Th1/Th2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α.

  • Exploratory: Overall Subject Outcome [ Time Frame: Up to 3 years ]
    Evaluate overall response by RECIST 1.1 including survival


Estimated Enrollment: 60
Actual Study Start Date: February 9, 2017
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
INT230-6 injections every 28 days for 5 sessions into only superficial tumors, low starting dose, low concentration per tumor.
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort B1
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, low starting dose, low drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort B2
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, medium starting dose, low drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort B3
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, high starting dose, low drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort C1
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, low starting dose, high drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort C2
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, medium starting dose, high drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort C3
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, high starting dose, high drug concentration per tumor
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Experimental: Cohort D
INT230-6 injections every 28 days for 5 sessions into superficial or deep tumors, dosing per any B or C cohorts (having acceptable tolerability) with addition of anti-PD-1 antibodies
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Biological: anti-PD-1
A concomitant anti-PD-1 will be added in cohort D
Experimental: Cohort E
INT230-6 injections every 14 days for 5 sessions into superficial or deep tumors treated, dosing per any B, C or D cohorts (having acceptable tolerability) an anti-PD-1 antibody could be added
Drug: INT230-6

INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.

The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.

The drug is stored frozen and must be dosed at room temperature.

Escalation of the drug dose and number of injected tumors is possible in subsequent treatment sessions.

The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Biological: anti-PD-1 antibody
A concomitant anti-PD-1 antibody could be added for cohort E

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

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:

  1. White Blood Cell (WBC) ≥2000/μL (≥2 x 10^9/L)
  2. Neutrophils ≥1000/μL (≥1 x 10^9/L)
  3. Platelets ≥70x103/μL (≥ 70 x 10^9/L) (superficial tumor dosing only)
  4. Hemoglobin ≥8 g/dL (≥80 g/L) (superficial tumor dosing only)
  5. Creatinine within the institution's laboratory upper limit of normal (ULN) or calculated creatinine clearance >50 ml/min
  6. alanine aminotransferase /aspartate aminotransferase (ALT/AST) ≤2.5 x ULN without, and ≤ 5 x ULN with hepatic metastases
  7. Bilirubin ≤2 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL (<52 µmol/L))
  8. For patients with planned deep tumor injections: prothrombin time (PT), activated partial thromboplastin time (aPPT), and international normalized ratio (INR) within normal limits; Platelet count ≥100,000/μL; hemoglobin ≥ 9 gm/dL.

    13. Additional criteria for cohort D (anti-PD1 combo) will be supplied in an appendix at a later date.

    Exclusion Criteria:

    1. History of severe hypersensitivity reactions to cisplatin or vinblastine or other products of the same class;
    2. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, or any other cancer from which the subject has been disease-free for at least 5 years;
    3. Underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events;
    4. Concurrent medical condition requiring the use of immunosuppressive medications, or systemic or topical corticosteroids; systemic or topical corticosteroids must be discontinued at least 4 weeks prior to enrollment. Inhaled or intranasal corticosteroids (with minimal systemic absorption may be continued if the subject is on a stable dose). Non-absorbed intra-articular steroid injections will be permitted; or use of other investigational drugs (drugs not marketed for any indication) within 30 days prior to study drug administration. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted;
    5. For deep tumor cohorts, patients who require uninterrupted anticoagulants of any type, on daily aspirin therapy, or NSAIAs.
    6. U.S. ONLY: For all Cohorts, patients who refuse approved therapy for which they are a suitable candidate are not eligible for enrollment on this trial.
    7. Additional criteria for cohort D (anti-PD1 combo) will be supplied in an appendix at a later date.
  Contacts and Locations
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): NCT03058289


Contacts
Contact: Jeanne Lewis 860-815-7185 jlewis@ce3inc.com
Contact: Lisa Kamen 203-605-1041 lkamen@intensitytherapeutics.com

Locations
United States, California
USC Norris Recruiting
Los Angeles, California, United States, 90033
Contact: Sherine Elsayegh    323-865-0465    sherine.elsayegh@med.usc.edu   
Contact: Jubilee Acap    323-865-0451    jubilee.acap@med.use.edu   
USC HOAG Recruiting
Newport Beach, California, United States, 92663
Contact: Alicia Bogardus    949-764-6755    Alicia.bogardus@hoag.org   
Contact: Cristina de Leon    9497645543    cristina.deleon@hoag.org   
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21205
Contact: Denise Gallagher, RN    410-502-5140    phase1trials@exchange.johnshopkins.edu   
Principal Investigator: Nilofer Azad, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Patricia Murphy    215-728-2195    Patricia.Murphy@fccc.edu   
Principal Investigator: Anthony J. Olszanski, MD, RPh         
Canada, Ontario
Princess Margaret Cancer Center - University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Helda Li    4169464501 ext 3823    helda.li@uhn.ca   
Sponsors and Collaborators
Intensity Therapeutics, Inc.
University of Southern California
University Health Network, Toronto
Investigators
Study Director: Ian B. Walters, M.D. Intensity Therapeutics
Study Chair: Lillian Siu, M.D., FRCP Princess Margaret Hospital, Canada
Principal Investigator: Anthony El-Khoueiry, M.D. USC Norris and HOAG sites
Principal Investigator: Anthony J. Olszanski, M.D., RPh Fox Chase Cancer Center
Principal Investigator: Nilofer Azad, M.D. Sidney Kimmel Comprehensive Cancer Center
  More Information

Responsible Party: Intensity Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03058289     History of Changes
Other Study ID Numbers: IT-01
First Submitted: February 10, 2017
First Posted: February 20, 2017
Last Update Posted: November 17, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Intensity Therapeutics, Inc.:
INT230-6
Neoplasm
Malignancy
Intratumoral
Intralesional
anti-PD-1 antibodies
Immuno therapy
Dose escalation
Platinum
Intensity Therapeutics
cisplatin
vinblastine
PD-1

Additional relevant MeSH terms:
Pancreatic Neoplasms
Glioblastoma
Head and Neck Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Liver Diseases
Antibodies
Immunoglobulins
Vinblastine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators