Trial Title:
CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer
NCT ID:
NCT05942300
Condition:
Recurrent Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Hypersensitivity
Recurrence
Carboplatin
Conditions: Keywords:
platinum sensitive
stromal tumor microenvironment (TME)
PARP inhibitor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CPI-0209
Description:
A second-generation EZH2 inhibitor that has been designed to achieve comprehensive
anti-cancer target coverage through extended on-target residence time.
Arm group label:
CPI-0209 (150 mg) + carboplatin
Arm group label:
CPI-0209 (200 mg) + carboplatin
Arm group label:
CPI-0209 (250 mg) + carboplatin
Other name:
Tulmimetostat
Intervention type:
Drug
Intervention name:
carboplatin
Description:
Carboplatin is a chemotherapy drug that contains the metal platinum. It stops or slows
the growth of cancer cells and other rapidly growing cells by damaging their DNA.
Arm group label:
CPI-0209 (150 mg) + carboplatin
Arm group label:
CPI-0209 (200 mg) + carboplatin
Arm group label:
CPI-0209 (250 mg) + carboplatin
Summary:
This is a clinical trial using CPI-0209 in combination with Carboplatin chemotherapy
followed by CPI-0209 maintenance in patients with platinum sensitive, recurrent ovarian
cancer.
Detailed description:
Clinically, there is a critical need for improved therapies in ovarian cancer. There has
been recent success with maintenance therapy in ovarian cancer with both PARP inhibitors
and bevacizumab approved in the up-front maintenance setting and in the recurrent,
platinum sensitive maintenance setting. However, it is unclear what treatment should be
used post-PARPi or bevacizumab maintenance. Additionally, the benefit derived from
bevacizumab maintenance therapy is modest with generally a few month improvement in
progression free survival. Further, there is emerging evidence that after progression on
a PARPi, there is decreased response to platinum-based therapy. This provides a critical
unmet need to enhance platinum response, particularly after previous maintenance therapy.
This also provides a large group of patients who could potentially benefit from EZH2
targeting agents to block stromal-mediated chemotherapy resistance and metastasis.
This study aims to investigate whether CPI-0209 will enhance ovarian cancer sensitivity
to platinum-based chemotherapy and prolong the disease free interval after completion of
chemotherapy by blocking stromal mediated chemotherapy resistance, metastasis promotion
and ovarian cancer growth.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal
cancer (defined as recurrent disease > 6 months after completing last platinum-
based chemotherapy) that are eligible to receive platinum-based chemotherapy).
- Documented disease recurrence/progression based on GCIG-RECIST
- Must have had at least 1 prior line of platinum-based therapy, prior bevacizumab or
PARPi use are allowed. Women with germline BRCA mutations should be considered for
PARPi maintenance as standard of care treatment prior to consideration of clinical
trial enrollment
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 with life
expectancy of ≥ 3months
- Adequate organ function
- Serum creatinine ≤1.5mg/dL or 24-hour clearance ≥50mL/min
- AST/ALT <2.5x ULN (or <5x ULN if liver metastasis are present)
- Total bilirubin ≤ ULN or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x
ULN in patients with well-documented Gilbert's Syndrome
- Hemoglobin ≥9 gm/dl, Platelets ≥100,000/μl ANC ≥1500/μl
- INR ≤1.5
- Potassium, total calcium (corrected for serum albumin), magnesium, and sodium
within normal limits for the institution or corrected to within normal limits
with supplements before first dose of study medication
- Must be able to swallow CPI-0209 tablet/oral suspension
- Able to provide informed consent and comply with all study protocol
- Treated CNS metastasis allowed if treatment is completed ≥8 weeks prior to
enrollment. Patients must be asymptomatic off systemic corticosteroids for at least
4 weeks after completion of radiation therapy. CNS disease must be stable or
regressed on repeat imaging performed at least 4 weeks after completion of therapy.
- Women of child-bearing potential (those who have had a menstrual cycle within the
last year and have not had a tubal ligation or surgical removal of both ovaries
and/or hysterectomy) must agree to abstain from vaginal intercourse or use and
continue highly effective methods of contraception for at least 183 days after
discontinuation of study treatment.
- Total abstinence when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone level
assessment.
- Male sterilization (at least 6 months prior to screening). The vasectomized
male partner should be the sole partner for that patient.
- Use of oral, injected or implanted hormonal methods of contraception or
placement of an intrauterine device (IUD) or intrauterine system (IUS), or
other forms of hormonal contraception that have comparable efficacy (failure
rate <1%), for example hormone vaginal ring or transdermal hormone
contraception.
- In case of use of oral contraception, women should have been stable on the same
pill for a minimum of 3 months before taking study treatment.
Exclusion Criteria:
- Borderline or low malignant potential histology
- Platinum-resistant disease (as defined as progressive disease (PD) within 6 months
of completion of chemotherapy with a platinum agent).
- Known hypersensitivity to any of the excipients of CPI-0209.
- Gastrointestinal (GI) dysfunction or disease that may significantly alter the
absorption of the study drugs
- Concurrent malignancy or malignancy within 3 years prior to starting study drug with
the exception of adequately treated basal or squamous cell carcinoma,
non-melanomatous skin cancer or curatively resected cervical cancer or per physician
discretion that the previous cancer was adequately treated with curative intent and
unlikely to recur (the study PI must concur with this determination).
- History of HIV infection
- Has an active infection requiring systemic treatment
- Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks and
contraindicate patient's participation in the clinical study or compromise
compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis,
active untreated or uncontrolled fungal, bacterial or viral infections, significant
cardiac/pulmonary disease etc.)
- Patient is currently receiving warfarin or other coumadin-derived anticoagulant for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH) or fondaparinux is allowed.
- Use of herbal supplements unless discontinued ≥7 days prior to initiation of study
drug
- Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to be
discontinued 7 days prior to initiation of study drug. Patients that are unwilling
to exclude Seville oranges, grapefruit juice, AND grapefruit from the diet and all
foods that contain those fruits from time of enrollment to through the duration of
study participation will be excluded.
- Pregnant or breast feeding
- Participation in a prior investigational study within 30 days prior to enrollment or
within 5 half-lives of the investigational product, whichever is longer
- Patient who has received radiotherapy ≤4 weeks or limited field radiation for
palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade
1 or better from related side effects of such therapy (exceptions include alopecia)
and/or in whom ≥25% of the bone marrow (Ellis, 1961) was irradiated.
- Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects (tumor biopsy is not considered as major surgery).
- Patient has not recovered from all toxicities related to prior anticancer therapies
to NCI-CTCAE version 5 Grade ≤1 (Exception to this criterion: patients with any
grade of alopecia, controlled endocrine toxicities and/or neuropathy ≤ grade 2 are
allowed to enter the study).
- Grade 3 baseline neuropathy
- Patient with a Child-Pugh score B or C.
Gender:
Female
Gender based:
Yes
Gender description:
Biological females
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Magee-Womens Research Institute / UPMC Magee Womens Hospital
Address:
City:
Pittsburgh
Zip:
15213
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelsey Mitch, RN
Phone:
412-623-6793
Email:
adamikka@upmc.edu
Contact backup:
Last name:
Joshua Plassmeyer, MS
Phone:
412-648-6417
Email:
plassmeyerjm@upmc.edu
Investigator:
Last name:
Lan Coffman, MD
Email:
Principal Investigator
Start date:
January 10, 2024
Completion date:
August 31, 2029
Lead sponsor:
Agency:
Lan Coffman
Agency class:
Other
Collaborator:
Agency:
MorphoSys AG
Agency class:
Industry
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of Pittsburgh
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05942300
