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Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies (COTI2-101)

Primary Purpose

Ovarian Cancer, Fallopian Tube Cancer, Endometrial Cancer

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
COTI2
Cisplatin
Sponsored by
Critical Outcome Technologies Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: HNSCC, with confirmed p53 mutations
    • Part 3: Gynecological malignancies, HNSCC, colorectal, lung, pancreatic cancer, or other tumors with Sponsor approval.
  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 1.5x upper limit of normal;
    • Partial thromboplastin time (PTT) within 1.5x upper limit of normal;
    • Total bilirubin within normal limits;
    • Alanine transaminase (ALT) and aspartate transaminase (AST) within 1.5x upper limit of normal;
    • 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)

Sites / Locations

  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

COTI2

COTI2 + cisplatin

Arm Description

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.

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 3 weeks of treatment as described (5 days on, 2 days off per week). Cisplatin 60 mg/m2 IV will be administered on Day 1 of each 3 week cycle. Participants will remain on treatment until they experience a lack of benefit.

Outcomes

Primary Outcome Measures

Number of dose limiting Toxicities
Used to measure safety and tolerability of COTI2
Tmax
To determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

Secondary Outcome Measures

Clinical response
This will be assessed through CT imaging, measurement using RECIST 1.0 criteria and GCIG criteria (if applicable)
Progression Free survival
This will be assessed through CT imaging and measurement using RECIST 1.0 criteria.

Full Information

First Posted
April 27, 2015
Last Updated
January 30, 2019
Sponsor
Critical Outcome Technologies Inc.
Collaborators
M.D. Anderson Cancer Center, Northwestern Memorial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02433626
Brief Title
Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies
Acronym
COTI2-101
Official Title
A Phase 1 Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Advanced or Recurrent Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 2015 (undefined)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Critical Outcome Technologies Inc.
Collaborators
M.D. Anderson Cancer Center, Northwestern Memorial Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Activity of COTI-2 has been demonstrated in various cancer tumor models. With its p53- and AKT-based mechanisms of action, COTI-2 is anticipated to be highly relevant in treatment of patients with gynecologic malignancies or head and neck squamous cell carcinoma (HNSCC) as well as a variety of other tumor types. This study is designed primarily to assess the safety and tolerability of COTI-2 monotherapy or combination therapy in patients with advanced and recurrent malignancies to establish a recommended Phase 2 dose (RP2D) for future studies. Patients are currently being recruited for Part 3 of the study. Critical Outcome Technologies Inc. has been renamed to Cotinga Pharmaceuticals.
Detailed Description
This is a three-part, multi-center, open-label, Phase 1, first-in-patient study of COTI-2 in patients with recurrent ovarian, fallopian tube, primary peritoneal, endometrial, or cervical cancer (collectively gynecological malignancies), and in patients with head and neck squamous cell carcinoma (HNSCC), colorectal, lung, or pancreatic cancer. Other tumor types may be allowed with Sponsor approval. COTI-2 will be self-administered as a single agent, orally, once daily for 5 days followed by 2 treatment-free days each week. Part 1 of the study will be dose finding in patients with gynecological malignancies using a 3 + 3 design to establish the MTD (maximum tolerated dose) over 6 planned cohorts. Part 2 of the study will be dose finding in patients with HNSCC using a 3 + 3 design to establish the MTD over 6 planned cohorts. Part 3 of the study will be dose finding for COTI-2 in combination with cisplatin in patients with gynecological malignancies, HNSCC, colorectal, lung, pancreatic cancer, or other tumor types with Sponsor approval.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tube Cancer, Endometrial Cancer, Cervical Cancer, Peritoneal Cancer, Head and Neck Cancer, HNSCC, Colorectal Cancer, Lung Cancer, Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
COTI2
Arm Type
Experimental
Arm Description
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.
Arm Title
COTI2 + cisplatin
Arm Type
Experimental
Arm Description
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 3 weeks of treatment as described (5 days on, 2 days off per week). Cisplatin 60 mg/m2 IV will be administered on Day 1 of each 3 week cycle. Participants will remain on treatment until they experience a lack of benefit.
Intervention Type
Drug
Intervention Name(s)
COTI2
Other Intervention Name(s)
CAS 1039455-84-9; 4-(2-pyridinyl)-2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide-1-piperazinecarbothioic acid
Intervention Description
COTI-2 is a third generation thiosemicarbazone.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
CAS 15663-27-1; CDDP
Intervention Description
Cisplatin is approved to treat a range of solid tumors and lymphomas.
Primary Outcome Measure Information:
Title
Number of dose limiting Toxicities
Description
Used to measure safety and tolerability of COTI2
Time Frame
12 months
Title
Tmax
Description
To determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Clinical response
Description
This will be assessed through CT imaging, measurement using RECIST 1.0 criteria and GCIG criteria (if applicable)
Time Frame
6 Months
Title
Progression Free survival
Description
This will be assessed through CT imaging and measurement using RECIST 1.0 criteria.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria ≥18 years of age. Willing and able to provide written informed consent to participate in this investigational study. 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: HNSCC, with confirmed p53 mutations Part 3: Gynecological malignancies, HNSCC, colorectal, lung, pancreatic cancer, or other tumors with Sponsor approval. Ability to attend all scheduled study visits 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. European Cooperative Oncology Group (ECOG) performance status 0 or 1. Life expectancy ≥3 months. 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 1.5x upper limit of normal; Partial thromboplastin time (PTT) within 1.5x upper limit of normal; Total bilirubin within normal limits; Alanine transaminase (ALT) and aspartate transaminase (AST) within 1.5x upper limit of normal; 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. 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. 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. 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). Patients enrolled in the expansion phase must be willing to undergo pre and post-Cycle 1 biopsies. Patients enrolled in the escalation and expansion phases will be required to have archival tissue available for analysis. Exclusion Criteria: Pregnant or lactating. 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. Inability to tolerate oral medications. 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. History of clinically significant or uncontrolled cardiac disease including but not limited to: Myocardial infarction, Angina pectoris, Congestive heart failure of New York Heart Association (NYHA) Grade >2, Ventricular arrhythmias requiring continuous therapy, or Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled. Major surgery, excluding skin biopsies and procedures for insertion of central venous access devices, within 28 days prior to the start of COTI-2. Active, uncontrolled bacterial, viral, fungal, or other opportunistic infection requiring systemic therapy. Part 2: The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place. HPV-positive status ( In HNSCC patients only)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Ho, MD-PhD
Email
rho@cotingapharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shannon Westin, MD
Organizational Affiliation
MD Anderson
Official's Role
Principal Investigator
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shannon Westin, MD
Phone
713-794-4314
First Name & Middle Initial & Last Name & Degree
Shannon Westin, MD

12. IPD Sharing Statement

Plan to Share IPD
No
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Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies

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