A Phase 1 Study of COTI-2 for the Treatment of Advanced and Recurrent Gynecologic Malignancies
The goal of this clinical research study is to find the highest tolerable dose of COTI-2 that can be given to patients with advanced or recurrent (has come back after treatment) endometrial, ovarian, peritoneal, or fallopian tube, and head and neck squamous cell carcinoma. The safety of this drug will also be studied. This is the first study using COTI-2 in humans.
Disease Group: Cervix,Endometrium,Fallopian Tube,Malignant neoplasms of eye brain and other parts of central nervous system,Malignant neoplasms of lip oral cavity and pharynx,Ovary,Peritoneum
Treatment Agent: COTI-2
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Breast & Ovarian Cancers Moon Shot,Critical Outcome Technologies Inc. (COTI)
Primary To evaluate the safety and tolerability of COTI-2 in patients with advanced or recurrent gynecologic malignancies and recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of COTI-2 for the treatment of patients with advanced or recurrent gynecologic malignancies and recurrent or metastatic HNSCC. Secondary To evaluate the pharmacokinetics of COTI-2 at all dose levels in patients with advanced or recurrent gynecologic malignancies and recurrent or metastatic HNSCC. To estimate the clinical activity of COTI-2 at all dose levels and at the RP2D in patients with advanced or recurrent gynecologic malignancies, and recurrent or metastatic HNSCC by response rate (Response Evaluation Criteria In Solid Tumors [RECIST] v1.1 criteria) and progression-free survival (PFS) rate at 6 months. To estimate the response duration for COTI-2 at all dose levels and at the RP2D in patients with advanced or recurrent gynecologic malignancies, and in patients with recurrent or metastatic HNSCC. Exploratory To determine if baseline molecular aberrations, including p53 mutation, correlate with activity of COTI-2 in advanced or recurrent gynecologic malignancies, and in patients with recurrent or metastatic HNSCC. To evaluate pharmacodynamic markers of COTI-2 activity at all dose levels and at the RP2D in patients with advanced or recurrent gynecologic malignancies, and in patients with recurrent or metastatic HNSCC.
IRB Review and Approval Date: 01/22/2016
Recruitment Status: Open
Projected Accrual: 92
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: Ovarian cancer or HNSCC, with confirmed p53 mutations
4) Ability and willingness to attend all scheduled and unscheduled study visits as required.
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 10^9/L; Platelet count >/=100 x 10^9/L; Prothrombin time (PT) or international normalized ratio (INR) </=1.5 x ULN; Partial thromboplastin time (PTT) </=1.5 x ULN; Total bilirubin within normal limits Alanine transaminase (ALT) and aspartate transaminase (AST) </=1.5 x ULN; Calculated creatinine clearance >50 mL/min; Urine protein <500 mg or urine protein: creatinine ratio (UPC) <1.0; and Left ventricular ejection fraction (LVEF by ECHO) >/= 55% (or the institutional lower limit of normal [LLN])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.
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: a. Myocardial infarction,b. Angina pectoris, c. Congestive heart failure of New York Heart Association (NYHA) Grade >2, d. Ventricular arrhythmias requiring continuous therapy, or e. 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 and 3: (a) The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place. (b) HPV-positive status (in HNSCC patients only)
Information and next steps
Cervix,Endometrium,Fallopian Tube,Malignant neoplasms of eye brain and other parts of central nervous system,Malignant neoplasms of lip oral cavity and pharynx,Ovary,Peritoneum
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