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

January 30, 2019 updated by: Critical Outcome Technologies Inc.

A Phase 1 Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Advanced or Recurrent Malignancies

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

51

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
          • Shannon Westin, MD
          • Phone Number: 713-794-4314

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other Names:
  • CAS 1039455-84-9; 4-(2-pyridinyl)-2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide-1-piperazinecarbothioic acid
Experimental: COTI2 + cisplatin
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.
Drug: COTI2
COTI-2 is a third generation thiosemicarbazone.
Other Names:
  • CAS 1039455-84-9; 4-(2-pyridinyl)-2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide-1-piperazinecarbothioic acid
Drug: Cisplatin
Cisplatin is approved to treat a range of solid tumors and lymphomas.
Other Names:
  • CAS 15663-27-1; CDDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of dose limiting Toxicities
Time Frame: 12 months
Used to measure safety and tolerability of COTI2
12 months
Tmax
Time Frame: 6 months
To determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response
Time Frame: 6 Months
This will be assessed through CT imaging, measurement using RECIST 1.0 criteria and GCIG criteria (if applicable)
6 Months
Progression Free survival
Time Frame: 12 months
This will be assessed through CT imaging and measurement using RECIST 1.0 criteria.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Critical Outcome Technologies Inc.

Collaborators

M.D. Anderson Cancer Center
Northwestern Memorial Hospital

Investigators

  • Principal Investigator: Shannon Westin, MD, MD Anderson

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

June 1, 2020

Study Registration Dates

First Submitted

April 27, 2015

First Submitted That Met QC Criteria

April 29, 2015

First Posted (Estimate)

May 5, 2015

Study Record Updates

Last Update Posted (Actual)

February 1, 2019

Last Update Submitted That Met QC Criteria

January 30, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COTI2-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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