AzTrials
AzTrials

Ovarian CancerPhase 1COTI2-101NCT02433626

Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies

A Phase 1 study testing COTI2 and Cisplatin in people with Ovarian Cancer and Fallopian Tube Cancer, run by Critical Outcome Technologies Inc. at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
COTI2 and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteUnited States
Study dates
Dec 2015to Jun 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥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.
Show all 26Show fewer
  • 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.

Who cannot join

  • 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,
Show all 15Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

Richard Ho, MD-PhD contact

rho@cotingapharma.com

United States1 site, 1 recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Shannon Westin, MD, 713-794-4314

    Shannon Westin, MD

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
COTI2, Cisplatin
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms, Endometrial Neoplasms, Uterine Cervical Neoplasms, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • COTI2Drug

    Also called CAS 1039455-84-9; 4-(2-pyridinyl)-2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide-1-piperazinecarbothioic acid

    COTI-2 is a third generation thiosemicarbazone.

  • CisplatinDrug

    Also called CAS 15663-27-1; CDDP

    Cisplatin is approved to treat a range of solid tumors and lymphomas.

Study groups in NCT02433626
Study groupRoleWhat they receive
COTI2ExperimentalCOTI-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.
Receives: Drug: COTI2
COTI2 + cisplatinExperimentalCOTI-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.
Receives: Drug: COTI2; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of dose limiting Toxicities

    Used to measure safety and tolerability of COTI2

    Measured: 12 months

  2. Tmax

    To determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

    Measured: 6 months

Secondary outcomes (2)

  1. Clinical response

    This will be assessed through CT imaging, measurement using RECIST 1.0 criteria and GCIG criteria (if applicable)

    Measured: 6 Months

  2. Progression Free survival

    This will be assessed through CT imaging and measurement using RECIST 1.0 criteria.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 May 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionDec 2019 (estimated)
  4. Study completionJun 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02433626
Sponsor's protocol ID
COTI2-101
Acronym
COTI2-101
Status last verified
Jan 2019
First submitted
27 Apr 2015
Last updated
1 Feb 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Andrews S, von Gruenigen VE. Management of the late effects of treatments for gynecological cancer. Curr Opin Oncol. 2013 Sep;25(5):566-70. doi: 10.1097/CCO.0b013e328363e11a.

    PubMed 23942302

  • Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166.

    PubMed 21720365

  • Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006 Oct 1;66(19):9339-44. doi: 10.1158/0008-5472.CAN-06-3126. Epub 2006 Sep 21. No abstract available.

    PubMed 16990346

  • Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, Heintz AP, Ngan HY, Pecorelli S. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006 Nov;95 Suppl 1:S105-43. doi: 10.1016/S0020-7292(06)60031-3. No abstract available.

    PubMed 17161155

  • Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev Anticancer Ther. 2009 Jul;9(7):905-16. doi: 10.1586/era.09.54.

    PubMed 19589030

  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

    PubMed 19097774

  • Freed-Pastor WA, Prives C. Mutant p53: one name, many proteins. Genes Dev. 2012 Jun 15;26(12):1268-86. doi: 10.1101/gad.190678.112.

    PubMed 22713868

  • Hirte HW, Strychowsky JE, Oliver T, Fung-Kee-Fung M, Elit L, Oza AM. Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a systematic review. Int J Gynecol Cancer. 2007 Nov-Dec;17(6):1194-204. doi: 10.1111/j.1525-1438.2007.00900.x. Epub 2007 Jun 1.

    PubMed 17540006

  • Kalsi JK, Manchanda R, Menon U. Screening for gynecological cancers. Expert Rev Obstet Gynecol 2013;8(2):143-60.

  • Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MDM, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L. Mutational landscape and significance across 12 major cancer types. Nature. 2013 Oct 17;502(7471):333-339. doi: 10.1038/nature12634.

    PubMed 24132290

  • 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.

  • Maleki Vareki S, Salim KY, Danter WR, Koropatnick J. Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit cross-resistance in human cancer cell lines. PLoS One. 2018 Jan 24;13(1):e0191766. doi: 10.1371/journal.pone.0191766. eCollection 2018.

    PubMed 29364966

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing COTI2 and Cisplatin in people with Ovarian Cancer and Fallopian Tube Cancer, run by Critical Outcome Technologies Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Richard Ho, MD-PhD (rho@cotingapharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of dose limiting Toxicities (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02433626, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in