RECRUITING

Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers

Talk to us

Conditions

Advanced Endometrial CarcinomaMetastatic Endometrial CarcinomaMetastatic Fallopian Tube CarcinomaMetastatic Platinum-Resistant Ovarian CarcinomaMetastatic Primary Peritoneal CarcinomaRecurrent Endometrial CarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Platinum-Resistant Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaStage III Uterine Corpus Cancer AJCC v8Stage IV Uterine Corpus Cancer AJCC v8

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial tests the safety, side effects, and best dose of combination therapy with pelcitoclax (APG-1252) and cobimetinib in treating patients with ovarian and endometrial cancers that have come back after a period of improvement (recurrent). APG-1252 is a drug that inhibits activity of proteins that prevent cell death, leading to increased cell death and reduced cell growth. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers.

Official Title

A Phase 1 Study of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers

Quick Facts

Study Start:2023-09-14
Study Completion:2026-06-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05691504

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:FEMALE
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * For dose escalation, patients must have histologically or cytologically confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, or endometrial cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. For expansion, patients must have histologically or cytologically confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer
  2. * Prior lines:
  3. * Patients must have received at least one prior line of platinum-based systemic therapy. Platinum received together with radiation as a sensitizing agent is not considered a systemic line of therapy
  4. * Patients with low grade serous ovarian cancer must have received a prior MEK inhibitor at a demonstrated therapeutic dose (i.e., trametinib 1mg daily or higher; binimetinib 30mg twice daily or higher). Patients who have had prior cobimetinib must have been able to tolerate cobimetinib at the dose and schedule they would receive it on study
  5. * Patients with microsatellite instability (MSI) or mismatch repair deficient (dMMR) endometrial cancer must have received prior PD-1 or PD-L1 directed immunooncology (IO) therapy or be considered medically ineligible to receive such therapy
  6. * Patients with ovarian cancer must have platinum-resistant disease (progression within 6 months of last receipt of platinum)
  7. * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of APG-1252 (pelcitoclax) in combination with cobimetinib in patients \< 18 years of age, children are excluded from this study
  8. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  9. * Absolute neutrophil count \>= 1,500/mcL
  10. * Platelets \>= 100,000/mcL
  11. * Hemoglobin \> 9 g/dL
  12. * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
  13. * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 3 x institutional ULN
  14. * Creatinine =\< 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 50 ml/min (based on the calculated Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) glomerular filtration rate estimation
  15. * Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal (LLN) (or above 50%, whichever is higher) by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
  16. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (that are not excluded) with undetectable viral load within 6 months are eligible for this trial
  17. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  18. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  19. * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression by scan and stable off systemic steroids for at least 4 weeks
  20. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  21. * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  22. * Patients should be able to swallow oral therapy
  23. * The effects of APG-1252 on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 2 weeks after completion of APG-1252 and cobimetinib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 2 weeks after completion of APG-1252 and cobimetinib administration
  24. * Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
  25. * Patients must be willing to release archival tissue if available
  26. * Patients on dose level 2 or higher in the escalation cohort and patients in the expansion cohort must have measurable and biopsiable disease (in a lesion that is not being utilized as a target lesion for Response Evaluation Criteria in Solid Tumors \[RECIST\] assessment)
  1. * Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment. Patients who have previously received cancer-directed therapeutic agents with the potential for CYP3A4 interaction will be eligible if at least 5 half-lives have elapsed before enrollment
  2. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
  3. * Patients who are receiving any other investigational agents
  4. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to APG-1252 or cobimetinib
  5. * Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of APG-1252 and cobimetinib. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  6. * Patients with uncontrolled intercurrent illness
  7. * Patients with evidence of retinal pathology on ophthalmologic examination; or neurosensory retinal detachment, right ventricular outflow (RVO), or neovascular macular degeneration
  8. * Pregnant women are excluded from this study because APG-1252 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with APG-1252, breastfeeding should be discontinued if the mother is treated with APG-1252. These potential risks may also apply to other agents used in this study
  9. * Patients with prior exposure to BCL family inhibitors
  10. * Patients with any gastrointestinal (GI) disorder that may affect absorption of cobimetinib and other oral medications in the opinion of the treating investigator, such as malabsorption syndrome, major bowel or stomach resection, evidence of small or large bowel obstruction within the past 3 months
  11. * Patients who have a dependence on IV fluids or total parenteral nutrition

Contacts and Locations

Principal Investigator

Joyce F Liu
PRINCIPAL_INVESTIGATOR
Dana-Farber - Harvard Cancer Center LAO

Study Locations (Sites)

Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States
Dana-Farber - Harvard Cancer Center LAO
Boston, Massachusetts, 02115
United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Joyce F Liu, PRINCIPAL_INVESTIGATOR, Dana-Farber - Harvard Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-14
Study Completion Date2026-06-01

Study Record Updates

Study Start Date2023-09-14
Study Completion Date2026-06-01

Terms related to this study

Additional Relevant MeSH Terms

  • Advanced Endometrial Carcinoma
  • Metastatic Endometrial Carcinoma
  • Metastatic Fallopian Tube Carcinoma
  • Metastatic Platinum-Resistant Ovarian Carcinoma
  • Metastatic Primary Peritoneal Carcinoma
  • Recurrent Endometrial Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Platinum-Resistant Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Stage III Uterine Corpus Cancer AJCC v8
  • Stage IV Uterine Corpus Cancer AJCC v8