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A Study of Coti-2 for the Treatment of Advanced or Recurrent Gynecologic Malignancies (COTI2-101)

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ClinicalTrials.gov Identifier: NCT02433626
Recruitment Status : Recruiting
First Posted : May 5, 2015
Last Update Posted : February 9, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

Activity of COTI-2 has been demonstrated in the OVCAR-3 ovarian cancer tumor model. With its p53- and AKT-based mechanisms of action, COTI-2 is anticipated to be highly relevant in treatment of patients with gynecologic malignancies.

This study is designed primarily to assess the safety and tolerability of COTI-2 in patients with advanced and recurrent gynecologic and head and neck malignancies and to establish a recommended Phase 2 dose (RP2D) for future studies.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Endometrial Cancer Cervical Cancer Peritoneal Cancer Head and Neck Cancer Drug: COTI2 Phase 1

Detailed Description:
This is a single arm, single center, open-label, Phase 1, first time in human study of COTI-2 in patients with recurrent ovarian,fallopian tube,primary peritoneal cancer, endometrial, cervical or head and neck cancer. COTI-2 will be self-administered as a single agent, orally, once daily for 5 days followed by 2 treatment-free days each week.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of COTI-2 for the Treatment of Advanced or Recurrent Gynecologic Malignancies.
Study Start Date : December 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: COTI2
COTI-2 will be self-administered as a single agent, orally, once daily for 5 days followed by 2 treatment-free days each week; 1 cycle will be defined as 4 weeks of treatment as described (5 days on, 2 days off per week). Participants will remain on treatment until they experience a lack of benefit.
Drug: COTI2
COTI-2 is a third generation thiosemicarbazone.

Outcome Measures

Primary Outcome Measures :
  1. Number of dose limiting Toxicities [ Time Frame: 12 months ]
    Used to measure safety and tolerability of COTI2

  2. Tmax [ Time Frame: 6 months ]
    To determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

Secondary Outcome Measures :
  1. Clinical response [ Time Frame: 6 Months ]
    This will be assessed through CT imaging, measurement using RECIST 1.0 criteria and GCIG criteria (if applicable)

  2. Progression Free survival [ Time Frame: 12 months ]
    This will be assessed through CT imaging and measurement using RECIST 1.0 criteria.

Eligibility Criteria

Information from the National Library of Medicine

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

Inclusion Criteria

  1. ≥18 years of age.
  2. Willing and able to provide written informed consent to participate in this investigational study.
  3. Cancer that is recurrent, metastatic, or unresectable and for which no effective or curative measures exist.

    • Part 1: Ovarian, fallopian tube, primary peritoneal, endometrial, or cervical cancer
    • Part 2: Ovarian or HNSCC, with histologically confirmed p53 mutations
  4. Ability to attend all scheduled study visits
  5. Measurable disease by physical examination or imaging as defined by RECIST v1.1 criteria or evaluable disease as defined by Gynecologic Cancer Intergroup (GCIG) CA125 criteria.
  6. European Cooperative Oncology Group (ECOG) performance status 0 or 1.
  7. Life expectancy ≥3 months.
  8. Adequate bone marrow, liver, renal, and cardiac function at study entry, assessed as follows:

    • Hemoglobin ≥9.0 g/dL;
    • Absolute neutrophil count (ANC) ≥1.5 x 109/L;
    • Platelet count ≥100 x 109/L;
    • Prothrombin time (PT) or international normalize rate (INR) within normal limits;
    • Partial thromboplastin time (PTT) within normal limits;
    • Total bilirubin within normal limits;
    • Alanine transaminase (ALT) and aspartate transaminase (AST) within normal limits;
    • Calculated creatinine clearance >50 mL/min;
    • Urine protein <500 mg or urine protein: creatinine ratio (UPC) <1.0; and
    • Left ventricular ejection fraction (LVEF) ≥55% (or the institutional lower limit of normal [LLN]) as evidenced on ECHO.
  9. Prior chemotherapy, other investigational agents, or radiation must be discontinued for at least 28 days prior to the first administration of COTI-2. Hormone treatments must be discontinued for at least 28 days prior to the first administration of COTI-2.
  10. Toxicity from prior therapy (except alopecia) has resolved to ≤Grade 1; in the event of toxicity that has not resolved to ≤Grade 1 but is considered stable, the patient may be eligible after discussion among the investigator and sponsor's medical monitor.
  11. Physiologically incapable of becoming pregnant, postmenopausal, or negative pregnancy test and agree to use adequate contraception (e.g., oral contraceptive, double barrier method, intra-uterine device, intra-muscular contraceptive).
  12. Patients enrolled in the expansion phase must be willing to undergo pre and post-Cycle 1 biopsies.
  13. Patients enrolled in the escalation and expansion phases will be required to have archival tissue available for analysis.

Exclusion Criteria:

  1. Pregnant or lactating.
  2. History of other invasive malignancies, with the exception of non-melanoma skin cancer or successfully treated in situ carcinoma, if there is evidence of the malignancy being present within the last 3 years.
  3. Inability to tolerate oral medications.
  4. Any serious and/or unstable pre-existing medical, psychiatric, or other condition (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
  5. History of clinically significant or uncontrolled cardiac disease including but not limited to:

    1. Myocardial infarction,
    2. Angina pectoris,
    3. Congestive heart failure of New York Heart Association (NYHA) Grade >2,
    4. Ventricular arrhythmias requiring continuous therapy, or
    5. Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled.
  6. Major surgery, excluding skin biopsies and procedures for insertion of central venous access devices, within 28 days prior to the start of COTI-2.
  7. Active, uncontrolled bacterial, viral, fungal, or other opportunistic infection requiring systemic therapy.
  8. Part 2:

    1. The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
    2. HPV-positive status ( In HNSCC patients only)
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): NCT02433626

Contact: Ashley ten Haaf 519-858-5157 atenhaaf@criticaloutcome.com

United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States
Principal Investigator: Wilberto Nieves-Neira, MD         
United States, Texas
MD Anderson Cancer Centre Recruiting
Houston, Texas, United States
Principal Investigator: Shannon Westin, MD         
Sponsors and Collaborators
Critical Outcome Technologies Inc.
M.D. Anderson Cancer Center
Northwestern Memorial Hospital
More Information

Kalsi JK, Manchanda R, Menon U. Screening for gynecological cancers. Expert Rev Obstet Gynecol 2013;8(2):143-60.
Leary A, Auclin E, Pautier P, Lhommé C. The PI3K/Akt/mTOR pathway in ovarian cancer: biological rationale and therapeutic opportunities. In: Ovarian cancer - a clinical and translational update. InTech; 2013, pp. 275-302.

Responsible Party: Critical Outcome Technologies Inc.
ClinicalTrials.gov Identifier: NCT02433626     History of Changes
Other Study ID Numbers: COTI2-101
First Posted: May 5, 2015    Key Record Dates
Last Update Posted: February 9, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Head and Neck Neoplasms
Uterine Cervical Neoplasms
Fallopian Tube Neoplasms
Endometrial Neoplasms
Neoplasms by Site
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Fallopian Tube Diseases
Adnexal Diseases