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

Phase 1

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

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

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:
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.
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:
1. The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
2. HPV-positive status ( In HNSCC patients only)

Arm && Interventions

Group	Intervention	Description
COTI2 + cisplatin	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 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.
COTI2	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.
COTI2 + cisplatin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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