Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT03586661 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2017-0404NCI-2018-01311
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the best dose and side effects of niraparib and copanlisib in treating patients with endometrial, ovarian, primary peritoneal, or fallopian tube cancer that has come back. Niraparib and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Endometrial Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Platinum-Resistant Ovarian Carcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Progressive Disease; Recurrent Endometrial Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Defined as the highest dose for which the posterior probability of toxicity is closest to 30%. Will employ the Bayesian optimal interval design. We will report the posterior probability of dose limiting toxicities (DLT) for each dose level and a 90% credible interval for the probability of DLT at each dose level.

  Up to 4 weeks

Study Arms (1)

Treatment (niraparib, copanlisib)

EXPERIMENTAL

Patients receive niraparib PO daily on days 1-28 and copanlisib IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Drug: Niraparib

Interventions

Copanlisib DRUG

Given IV

Also known as: BAY 80-6946, PI3K Inhibitor BAY 80-6946

Treatment (niraparib, copanlisib)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Treatment (niraparib, copanlisib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any histologically confirmed recurrent endometrial adenocarcinoma (except for carcinosarcoma), recurrent high-grade serous ovarian/primary peritoneal/fallopian tube carcinoma, or deleterious BRCA mutant recurrent ovarian/primary peritoneal/fallopian tube cancer for whom no curative option is available will be eligible. DOSE ESCALATION ONLY: For patients with ovarian cancer in the dose escalation cohort, only patients with recurrent, platinum resistant disease are eligible to enroll on study. Platinum resistance is defined as progression within 6 months from completion of platinum based therapy (the date should be calculated from the last administered dose of platinum therapy). In addition, patients in this cohort with a BRCA mutation must have also progressed after treatment with PARP inhibitor.
• Patients may have unlimited prior chemotherapeutic regimens for management of recurrent endometrial or ovarian carcinoma. Patients who have received prior PARP inhibitors ARE allowed to participate. Patients who have received prior PI3K-pathway inhibitors ARE allowed to participate on the dose escalation phase ONLY. Patients may have progressed on prior PARP inhibitor and/or PI3K-pathway inhibitor but they may not have discontinued drug for toxicity.
• With the exception of alopecia, peripheral neuropathy, and bone marrow parameters, any unresolved toxicities from prior chemotherapy should be no greater than Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) grade 1 at the time of starting study treatment.
• Patients should have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. If no measurable disease is present, patients should have assessable disease such as pleural effusion, ascites, with CA125 Gynecological Cancer Intergroup (GCIG) criteria.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• The effects of niraparib and copanlisib on the developing human fetus are unknown. For this reason, women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to taking study treatment. Female patients and their male partners must also agree to use effective contraception when sexually active. This applies since signing of the informed consent form and 6 months (for women of child bearing potential) after the last study drug administration. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
• A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. The investigator or a designated associate must advise the patient (WOCBP or men who have not undergone bilateral orchidectomy) how to achieve highly effective birth control method. Birth control should be used from the signing of the patient consent form and for 180 days following the last dose of niraparib. Acceptable methods of birth control include:
• Two highly effective forms of contraception, defined as contraceptive methods with a failure rate of less than 1% per year when used consistently and correctly. Patients and their sexual partners who've undergone vasectomy or tubal occlusion must also use a male condom with spermicide.
• Permanent sterilization, defined as hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral orchidectomy; postmenopausal, defined as a female patient or sexual partner \> 45 years of age who has not menstruated for at least 12 consecutive months; total sexual abstinence.
• It is unknown if niraparib or copanlisib are expressed in human breast milk. For this reason, women must not breast-feed while taking the study medications.
• Absolute neutrophil count \>= 1,500/mcL (within 7 days prior to entry/randomization).
• Hemoglobin \>= 9 gm/dL (within 7 days prior to entry/randomization).
• Platelets \>= 100,000/mcL (within 7 days prior to entry/randomization).
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 7 days prior to entry/randomization) (\< 2 x ULN for patients with Gilbert-Meulengracht syndrome or for patients with cholestasis due to compressive adenopathies of the hepatic hilum).
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN unless the liver is involved with tumor, in that case, ALT/AST must be =\< 5 x ULN (within 7 days prior to entry/randomization).

You may not qualify if:

• Patients must not be simultaneously enrolled in an interventional clinical trial.
• Patients with endometrial cancer may not have carcinosarcoma.
• Patients who have recurrences that are amenable to potentially curative treatment with radiation therapy or surgery.
• Patients who have a history of other malignancies except for basal cell or squamous cell skin cancer, in situ cervical cancer, unless they have been disease-free for at least three years. Patients may have dual primaries of ovarian and endometrial cancer, superficial bladder, or localized prostate cancer.
• Patients who have had prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents within 28 days of starting study treatment or autologous transplant less than 3 months before start of treatment unless evidence of progression since last treatment (not including palliative radiotherapy at focal sites) or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
• Patients who have had major surgery within 3 weeks prior to entry into the study or be recovering from any effects of surgery. Patients may not have had minor surgery within 2 weeks or open biopsy less than 7 days prior to entry into the study.
• Patients with known hypersensitivity to niraparib or copanlisib or any of their excipients. Patients may not have history of hypersensitivity to drugs with a similar chemical structure or class to niraparib or copanlisib.
• Patients who have experienced intolerable adverse events per treating investigator due to other PARP inhibitors or PI3K-pathway inhibitors.
• Patients with known history of cancer involvement of the central nervous system. A scan to confirm absence of brain metastasis is not required.
• Congestive heart failure \> New York Heart Association (NYHA) class 2.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), myocardial infarction less than 6 months before start of test drug Uncontrolled hypertension (despite optimal medical management).
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment.
• Non-healing wound, ulcer, or bone fracture.
• Glycosylated hemoglobin (HbA1c) \> 8.5% at screening.
• Known history of human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Sun C, Fang Y, Labrie M, Li X, Mills GB. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans. 2020 Jun 30;48(3):1101-1108. doi: 10.1042/BST20191092.

  PMID: 32379297 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Disease Progression; Endometrial Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

copanlisib; niraparib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Fallopian Tube Diseases; Adnexal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Shannon N Westin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 13, 2018
• Study Start: April 29, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)