INVINCIBLE TRIAL: Intratumoral INT230-6 in Breast Cancer

NCT04781725 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: OTT 20-11 (IT-02)
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, randomized, multi-center, parallel design, window of opportunity trial evaluating intratumoral INT230-6 in up to 90 patients with early stage breast cancer. In a 2:1 randomization, patients on the treatment arm will receive intratumoral INT230-6 injections prior to breast surgery.

Conditions

Breast Cancer

Keywords

window of opportunity; intratumoral; Ki67; complete pathologic response (PCR); immune activation; INT230-6; cisplatin; vinblastine; cell cycle arrest

Outcome Measures

Primary Outcomes (1)

• The proportion of patients achieving a CCCA defined as a reduction in the proportion of cells staining positive for Ki67 as assessed by immunohistochemistry to less than a natural logarithm, or ≤2.7%, at the post-treatment specimen.

  Tumor's viable plus necrotic tissue, at the post-treatment specimen.

  presurgical window (period from diagnosis to surgery window of 3-6 weeks)

Secondary Outcomes (4)

• The proportion of patients that achieved a complete pathologic response on surgical pathology as measured by the residual cancer burden index

  presurgical window (period from diagnosis to surgery of 3-6 weeks)

• Immunohistochemical and gene expression markers of necrosis, apoptosis and tumor proliferation pathways.

  presurgical window (period from diagnosis to surgery of 3-6 weeks)

• Markers of immunomodulation including macrophages, NK, DC, CD4 T-cells, CD8 T-cells, regulatory T-cells.

  presurgical window (period from diagnosis to surgery of 3-6 weeks)

• Adverse effects of INT230-6 injected to breast cancers in healthy patients prior to surgery.

  presurgical window (period from diagnosis to surgery of 3-6 weeks)

Study Arms (2)

INT230-6 Treated Arm

EXPERIMENTAL

Part I: Patients will receive up to 3 doses of INT230-6 injected weekly prior to breast surgery Part II: Patients will receive up to 2 intratumoral doses of INT230-6 (over a 15-day period) prior to breast surgery

Drug: INT230-6; Other: Saline injection

Control Arm

PLACEBO COMPARATOR

Part I: No intervention while awaiting surgery Part II: Placebo saline injection

Other: Saline injection

Interventions

INT230-6 DRUG

INT230-6 is a formulation of two well known chemotherapeutic agents, cisplatin (0.5mg/mL) and vinblastine sulfate (0.1mg/mL), combined with 2-hydroxybenzoylaminooctanoate (also known as SHAO-FA or SHAO as a sodium salt at 10mg/mL).

Also known as: Cisplatin, Vinblastine, 2-hydroxybenzoylaminooctanoate (SAHO)

INT230-6 Treated Arm

Saline injection OTHER

Standard 0.9 % NaCl Normal Saline

Control Arm; INT230-6 Treated Arm

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery.
• Patients with early, operable stage I to II breast cancer amendable for complete surgical resection as assessed by treating surgical oncologist.
• Tumors must be clinically palpable by surgeon. Part I: ≥ 1.0 cm by palpation or on imaging. Part II: ≥ 1.5 cm by palpation or on imaging.
• Histologic Bloom Richardson grade ≥2.
• \. Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS).
• \. ECOG PS 0-2 (Appendix A). 6. The participant (or legally acceptable representative if applicable) is able to provide written informed consent for the study.

You may not qualify if:

• Locally advanced or metastatic breast cancer.
• Prior therapy with chemotherapy or planned neoadjuvant chemotherapy.
• Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive carcinoma NOS.
• Patients with an active infection.
• Absolute Neutrophil Count \< 1.5 x 10\^9/L.
• Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m2.
• Any serious known immediate or delayed hypersensitivity reaction(s) to vinblastine or cisplatin or idiosyncrasy to drugs chemically related to the investigational drugs.
• Known allergic reaction to local anesthetic (Xylocaine, Marcaine).
• Concurrent medical condition requiring the use of immunosuppressive medications, or systemic corticosteroids at doses of greater than 10 mg Prednisone-equivalent Topical steroids and other localized corticosteroids are permitted. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted.
• Concurrent use of a prohibited medication or planned use of any forbidden medications during treatment with INT230-6, or within 4 weeks prior to study drug administration, which include chemotherapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer: systemic or intratumoral), other biologic therapy, investigational therapy, or hormonal therapy, cisplatin containing agents, and vinblastine containing agents while on treatment in this study. Other prohibited concomitant medications that will interact with vinblastine and cisplatin include mitomycin, phenytoin, CYP3A4 inhibitors (ketoconazole, voriconazole, clarithromycin, erythromycin), nephrotoxic drugs (aminoglycosides, amphotericin), or pure pyridoxine (pyridoxine contained in multivitamin is permitted). Use of other investigational drugs (drugs not marketed for any indication) within 4 weeks prior to study drug administration not permitted.
• Pregnancy if patient is of childbearing age) or breast feeding.
• Subjects with signs/symptoms suggestive of COVID-19 or known COVID-19 positive contacts in the past 14 days would be tested as per local Public Health and/or Institutional Guidelines. If patients are COVID-19 positive at the time of screening, they would be excluded from the trial.
• Any 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, or renders the patient ineligible to be on study.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Intensity Therapeutics, Inc.: collaborator
• Ontario Institute for Cancer Research: collaborator

Study Sites (1)

The Ottawa Hospital Research Institute and Cancer Center

Ottawa, Ontario, K1Y 4E9, Canada

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Pathologic Complete Response

Interventions

Cisplatin; Vinblastine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorides; Hydrochloric Acid; Sodium Compounds

Study Officials

• Angel Arnaout, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Arif Awan, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angel Arnaout, MD

CONTACT

6137985555; anarnaout@toh.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: March 4, 2021
• Study Start: March 25, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2023
• Last Updated: November 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)