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

NCT02433626 | Unknown Phase 1

• 1 other identifier: COTI2-101
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Endometrial Cancer; Cervical Cancer; Peritoneal Cancer; Head and Neck Cancer; HNSCC; Colorectal Cancer; Lung Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Number of dose limiting Toxicities

  Used to measure safety and tolerability of COTI2

  12 months

• Tmax

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

  6 months

Secondary Outcomes (2)

• Clinical response

  6 Months

• Progression Free survival

  12 months

Study Arms (2)

COTI2

EXPERIMENTAL

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

COTI2 + cisplatin

EXPERIMENTAL

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; Drug: Cisplatin

Interventions

COTI2 DRUG

COTI-2 is a third generation thiosemicarbazone.

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

COTI2; COTI2 + cisplatin

Cisplatin DRUG

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

Also known as: CAS 15663-27-1; CDDP

COTI2 + cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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;

You may not qualify if:

• 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)

Sponsors & Collaborators

• Critical Outcome Technologies Inc.: lead
• M.D. Anderson Cancer Center: collaborator
• Northwestern Memorial Hospital: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (12)

• 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.

  PMID: 23942302 BACKGROUND

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

  PMID: 21720365 BACKGROUND

• 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.

  PMID: 16990346 BACKGROUND

• 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.

  PMID: 17161155 BACKGROUND

• 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.

  PMID: 19589030 BACKGROUND

• 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.

  PMID: 19097774 BACKGROUND

• 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.

  PMID: 22713868 BACKGROUND

• 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.

  PMID: 17540006 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 24132290 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 29364966 BACKGROUND

MeSH Terms

Conditions

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; Pancreatic Neoplasms

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Shannon Westin, MD

  MD Anderson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Ho, MD-PhD

CONTACT

rho@cotingapharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: May 5, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: February 1, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)