Recruiting PHASE2 Recurrent Endometrial Carcinoma

New treatment option for Recurrent Endometrial Carcinoma

Official title Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial

ClinicalTrials.gov ID: NCT05554328

What this study is testing

What is Olaparib?

Olaparib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for recurrent endometrial carcinoma.

Also referred to as AZD 2281, AZD-2281.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: This phase II ComboMATCH treatment trial compares selumetinib plus olaparib to selumetinib alone in women with endometrial or ovarian (fallopian tube and primary peritoneal) cancer that has come back (recurrent) or that remains despite treatment (persistent) and harbors a mutation in the RAS pathway. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Phase 2: a mid-size study of how well it works
Which group you join is decided by chance.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older, women only

You may be able to join if

Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N4 based on the presence of an...
Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
Patients must have RAS pathway mutations as determined by the ComboMATCH screening assessment
Cohort 1: Patients with histologically confirmed RAS pathway mutant ovarian, primary peritoneal, or fallopian tube ("ovarian") cancer (activating...
Cohort 2: Patients with histologically confirmed RAS pathway mutant endometrial cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2...

You likely can't join if

Patients who have received any MEK inhibitors
Patients who have progressed while receiving a PARP inhibitor
Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception...
Patients with uncontrolled intercurrent illness
Patients with \>= grade 2 neuropathy within 14 days of registration

See the full eligibility criteria

Who can join

Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N4 based on the presence of an actionable mutation as defined in EAY191
Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
Patients must have RAS pathway mutations as determined by the ComboMATCH screening assessment
Cohort 1: Patients with histologically confirmed RAS pathway mutant ovarian, primary peritoneal, or fallopian tube ("ovarian") cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or inactivating...
Cohort 2: Patients with histologically confirmed RAS pathway mutant endometrial cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or inactivating mutations in NF1)
Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration...
Patients must have progressed after first-line treatment for recurrent or persistent disease
Patients with ovarian cancer should not be eligible for further platinum-based therapy
Patients with endometrial cancer must have received or been offered an immune oncology agent (alone or in combination with lenvatinib) unless there are existing contraindications for immune oncology agents or lenvatinib
Patients may have received unlimited prior therapy
Patients must have measurable and biopsiable disease. Measurable disease is defined by RECIST 1.1 as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each...
Patients must have at least one "target lesion" separate from the lesion to be biopsied to be used to assess response on this protocol as defined by RECIST version 1.1. Tumors within a previously irradiated field will...
Prior therapy must have been completed at least four weeks prior to registration
Age \>= 18
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
Hemoglobin (Hgb) \>= 9.5 g/dL with no blood transfusion in the past 28 days (within 14 days prior to registration)
Platelets \>= 100,000/mcl (within 14 days prior to registration)
Absolute neutrophil count (ANC) \>= 1,500/mcl (within 14 days prior to registration)
Patients must have creatinine clearance estimated of \>= 50 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (within 14 days prior to registration)
Total bilirubin level =\< 1.5 x institutional upper limit of normal (ULN) or =\< 3 x ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) (within 14 days prior to registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (within 14 days prior to registration)
Patients must be able to swallow and retain oral medications and be without gastrointestinal illnesses that would preclude absorption of selumetinib or olaparib
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...
Women of childbearing potential (WOCBP) must agree to use two forms of birth control (hormonal or barrier method of birth control; abstinence) during the study and for 6 months after completing treatment
Non-sterilized male partners of WOCBP (including males sterilized by a method other than bilateral orchidectomy e.g., vasectomy) who intend to be sexually active with a female partner must be using an acceptable method...
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
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
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is...
Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression
Extra caution should be taken with olaparib, as it crosses the blood brain barrier and can cause edema in brain metastases
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal...

What rules you out

Patients who have received any MEK inhibitors
Patients who have progressed while receiving a PARP inhibitor
Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
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
Patients with uncontrolled intercurrent illness
Patients with \>= grade 2 neuropathy within 14 days of registration
Patients with severe (Child-Pugh C) liver dysfunction
Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib and selumetinib or any excipients thereof
Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz...
Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for...
Vitamin E must not be taken in the 7 days prior to initiation of treatment with selumetinib
Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)...
Concomitant use of strong CYP2C19 inhibitors (e.g., ticlopidine) or moderate CYP2C19 inhibitors (e.g., omeprazole). The required washout period prior to starting selumetinib is at least 14 days or 5 half-lives...
Have received or are receiving an investigational medicinal product (IMP) or other systemic anti-cancer treatment (including chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, or...
Known myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
Patients who have had previous organ transplant, allogenic bone marrow transplant or double umbilical cord blood transplantation
Patients who have had whole blood transfusion within 28 days prior to registration
Patients with ophthalmological conditions as follows:
Current or past history of retinal pigment epithelial detachment/central serous retinopathy or retinal vein occlusion.
Intraocular pressure \> 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of intraocular pressure [IOP]). people with known glaucoma and increased IOP who do not have meaningful vision (light...
Patients with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility
Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or longstanding orbito-temporal plexiform neurofibroma (PN) (such as visual loss...
Patients with severe, active co-morbidity defined as any of the following:
History and/or confirmed pneumonitis
Uncontrolled hypertension (blood pressure [BP] \>= 150/90 mmHg despite medical therapy)
Acute coronary syndrome within 6 months prior to registration
Uncontrolled atrial fibrillation
Known family history of long QT syndrome
Women who are pregnant or unwilling to discontinue nursing

The study team makes the final eligibility decision.

Where it's taking place

Birmingham, Alabama, United States
Mobile, Alabama, United States
Anchorage, Alaska, United States
Goodyear, Arizona, United States
Kingman, Arizona, United States
Arroyo Grande, California, United States
Los Angeles, California, United States
Orange, California, United States
Palo Alto, California, United States
Whittier, California, United States
Aventura, Florida, United States
Coral Gables, Florida, United States
Deerfield Beach, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
North Miami, Florida, United States
Plantation, Florida, United States
Honolulu, Hawaii, United States
‘Ewa Beach, Hawaii, United States
Boise, Idaho, United States

+ 215 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling female, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Birmingham, Alabama, United States; Mobile, Alabama, United States; Anchorage, Alaska, United States; Goodyear, Arizona, United States; Kingman, Arizona, United States; Arroyo Grande, California, United States and 229 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.