Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Blood and Lymph Conditions

Immune System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Prostatic Neoplasms

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, T-Cell

Lymphoma, Large B-Cell, Diffuse

Lymphoproliferative Disorders

Mesothelioma

Mesothelioma, Malignant

Lymphoma, B-Cell

Adenocarcinoma, Clear Cell

Prostatic Neoplasms, Castration-Resistant

Adenomyoepithelioma

Neoplasms by Histologic Type

Immunoproliferative Disorders

Lymphatic Diseases

Endometrial Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Malignant Mesothelioma

Epithelial-myoepithelial Carcinoma

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M1: patients with urothelial carcinoma or other advanced/metastatic solid tumors (with known ARID1A mutation)

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M2 patients with ovarian clear cell carcinoma (with known ARID1A mutation)

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M3 patients with endometrial carcinoma (with known ARID1A mutation)

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M4 patients with peripheral T-cell lymphoma (PTCL) and patients with diffuse large B-cell lymphoma (DLBCL), including patients with documented germinal center B cell like diffuse large B-cell lymphoma (GCB-DLBCL) with at least 1 EZH2 hotspot mutation

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M5 patients with relapsed or refractory malignant pleural or peritoneal mesothelioma with known BAP1 loss

CPI-0209 will be dosed once per day orally in 28 day cycles.

• Cohort M6 patients with castration-resistant prostate cancer(mCRPC) with measurable soft tissue disease

CPI-0209

Medical Information

Adam Burgess

R. Donald Harvey, MD

Iryna Kobrynets

Hedy Kindler, MD

Terry Liu

Ryan Sullivan, MD

Brian Rasp

Alok Tewari, MD

Yvette S Cole, MPH

Yvette Cole, RN

Nehal Lakhani, MD

Celina Joco

Martin Gutierrez, MD

Stephen Cumberbatch

Salman Punekar, MD

Janet Garza, RN

Carrie Choi, RN

Drew Rasco, MD

Chrystal Axford

Linda Duska, MD

Chun-Fang Qiu

Charles Drescher, MD

Elizabeth Liu

Kalyan Banda, MD

Laura Wanner

Antoine Italiano

Solaya Chalal

Cyril Abdeddaim

Emilie Repetto

Mehdi Brahmi

Helene Godet

Thomas Gastinne, MD

Claire Peluchon

Thomas Gastinne

Tiphaine Chiron

Lucie-Anne Casper

Lauriane Eberst

Mariem Labiadh

Vincent Ribrag, MD

Silvia Corazza

Pier Luigi Zinzani, MD

Laura Paladini

Carmelo Carlo-Stella

Giulia Ferrara

Domenica Lorusso

Mina Jang

Jae-Hoon Kim

Marta Grubiak

Ewa Kalinka

Justyna Zwierzchowska

Marek Kotlarski, MD

Karolina Kolakowska

Jan Walewski, MD

Manuel Delgado Criado

Martin Garcia-Sancho, MD, PhD

Carolina Garcia Martinez

Teresa Curiel Garcia

Laia Gispert (Hematology)

Albert Meire (Oncology)

Francesc Bosch Albareda

Nuria Martin

Maria Pilar Barretina Ginesta

Maria Aleman Ramos

Antonio Gonzalez Martin

Irene Pascual

Luis Manso Sanchez

Uxue Nunez

Valentina Boni

Neomi Ceron Pisa

Jesus Alarcon

Mercedes Egana Gorraiz

Ana Landa Magdalena

Montserrat Dominguez

Alejandro Falcon Gonzalez

Lidia Riquelme

Angel Guerrero Zotano

Samantha Curtis

Rebecca Bowen

Sarah Porter

Harriet Walter, MD

Amy Pearce

Andrew Clamp

Abiramy Neduncheliyan

Susana Banerjee

Tamlyn Russel

Emma Cattell

First-in-human, open-label, sequential dose escalation and expansion study of CPI-0209 in patients with advanced solid tumors and lymphomas. CPI-0209 is a small molecule inhibitor of EZH2.

Emerging evidence suggests that EZH2 is overexpressed in many cancer types and has a pivotal role in disease progression. This is a Phase 1/2, open-label, multi-center, FIH study designed to evaluate the safety and tolerability and preliminary clinical activity of CPI-0209, an EZH2/1 inhibitor as monotherapy in patients with advanced solid tumors and lymphomas. Phase 1 is composed of a CPI-0209 Dose Escalation period in patients with advanced tumors and aims to determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of CPI-0209 as monotherapy in patients with advanced tumors.

Phase 2 is planned to evaluate safety and tolerability and antitumor activity of CPI-0209 in six disease-specific cohorts (M1 to M6). Patients in Cohorts M1, M2, M3, M5, and M6 will be enrolled at 10 to 29 patients per cohort, using a Simon 2-stage design. Cohort M4 will enroll up to 20 patients with lymphoma in a single-stage. The primary aim of Phase 2 part of the study is to evaluate the antitumor activity of CPI-0209, and characterize the safety and tolerability of CPI-0209 as monotherapy in patients with selected tumors.

In Phase 2, two additional doses are planned to be evaluated in cohorts M2 and M3 in 2 stages: Stage 2a and Stage 2b. In Stage 2a approximately 20 patients will be enrolled per cohort and will be randomized 1:1 to receive 2 prespecified dose levels of CPI-0209 once daily. When protocol criteria for initiating Stage 2b will be fulfilled after completion of Stage 2a, then Stage 2b will be opened for enrolment of additional 10 patients in one or both dose arms in each of the two cohorts. Thus, up to 40 patients per cohort (M2 and M3) could be enrolled.

A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas

A Phase 1/2 Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas

The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CPI-0209 in patients with advanced tumors

ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1 or applicable response criteria

ORR, defined as proportion of patients with a best overall response of CR or PR) based on RECIST 1.1 or applicable response criteria

ORR per Gynecologic Cancer Intergroup (GCIG)-defined CA-125 response criteria (ovarian cancer patients)

ORR per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)

PFS, defined as the time from first dose to confirmed disease progression or death

DOR, defined as the time from the date of first response to the date of confirmed disease progression

Time to response, defined as the time from first dose to date of first response

\[Disease control rate, defined as the proportion of patients with a best overall response of CR, PR, or stable disease

TTR, defined as the time from first dose to date of first response

Disease control rate, defined as the proportion of patients with a best overall response of CR, PR or SD per cohort and CPI-0209 dose level

ORR per GCIG-defined CA-125 response criteria (ovarian cancer patients)

OS, defined as the time from first dose to death

Number of Participants With Adverse Events (AEs)

Constellation Pharmaceuticals

Digestive System Diseases

Colorectal Neoplasms

Colonic Diseases

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Digestive System Neoplasms

Rectal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Vitamins

Herbal and Botanical

Ascorbic Acid

Irinotecan

Camptothecin

Trace Elements

Antioxidants

Enzyme Inhibitors

Protective Agents

Topoisomerase I Inhibitors

Vitamin C

Cola

Ascorbic Acid (50-100g, 3x weekly) with 350mg/m2 irinotecan once a week every 3 weeks

350mg/m2 irinotecan once a week every 3 weeks

Daniel A Monti, MD

This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with irinotecan versus treatment with irinotecan alone in patients with recurrent or advanced colorectal cancer who have failed at least one treatment regimen with a 5-FU based therapy. This study will be conducted as an amendment to Investigational New Drug # 77486.

Phase I: To assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated. This aim will be assessed by enrolling a minimum of 6 subjects meeting inclusion criteria, using a modified 3+3 design. Safety will be assessed with the following: toxicity graded by the NCI CTC, urinalysis pre- and post-infusion, basic metabolic panel, and CBC. From our experience and in the experience of our study collaborators, we hypothesize that the combination of IV AA with irinotecan will not be associated with adverse events.

Phase II: To utilize CT or PET/CT (when available) scans to evaluate disease progression to assess overall tumor response rate (complete and partial response) in subjects with advanced or recurrent colorectal cancer treated with the combination of ascorbic acid and irinotecan versus irinotecan alone.

Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA

Phase I/II Study of Intravenous Ascorbic Acid in Combination With Irinotecan Versus Irinotecan Alone for Advanced Colorectal Cancer

Safety: The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer

Thomas Jefferson University

The study was closed early due to lack of accrual. Adverse event data were collected for the patients who were enrolled in the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas	NCT04104776	Advanced Solid ... Diffuse Large B... Lymphoma, T-Cel... Mesothelioma, M... Prostatic Neopl... Endometrial Can... Ovarian Clear C...	CPI-0209	18 Years -	Constellation Pharmaceuticals
Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA	NCT01550510	Stage IV Colore...	Ascorbic Acid Irinotecan	18 Years -	Thomas Jefferson University
Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA	NCT01550510	Stage IV Colore...	Ascorbic Acid Irinotecan	18 Years -	Thomas Jefferson University

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