• Provision of informed consent prior to any study specific procedures

• Histologically-confirmed recurrent ovarian, fallopian tube, primary peritoneal cancer, endometrial, vaginal, or cervical cancer in the abdomen and pelvis

• Subjects with stage IV disease are eligible as long as disease elsewhere (other than the site(s) to receive radiation therapy \[RT\]) is undetectable or stable (\>= 3 months) and immediate chemotherapy is not required. Willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies at least three weeks prior to start of investigational therapy

• Hemoglobin \>= 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomization (choose whichever is most applicable to the study) (within 28 days prior to administration of study treatment)

• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 28 days prior to administration of study treatment)

• No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear (within 28 days prior to administration of study treatment)

• White blood cells (WBC) \> 3 x 10\^9/L (within 28 days prior to administration of study treatment)

• Platelet count \>= 100 x 10\^9/L (within 28 days prior to administration of study treatment)

• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be =\< 5 x ULN (within 28 days prior to administration of study treatment)

• Serum creatinine =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

⁃ Note: If cannot fulfill ECOG 0-1, must fulfill inclusion criteria below (minimum life expectancy of \>= 16 weeks)

• Patients must have a life expectancy \>= 16 weeks

• Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Postmenopausal is defined as:

⁃ Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50, radiation-induced oophorectomy with last menses \> 1 year ago, chemotherapy-induced menopause with \> 1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)

• Patient of child-bearing potential is willing to adhere to using two forms of highly effective birth control. Condoms with spermicide and one of the following are acceptable: oral contraceptive or hormonal therapy or placement of an intrauterine device (IUD). Acceptable non-hormonal birth control methods include: total sexual abstinence, vasectomized sexual partner plus male condom, tubal occlusion plus male condom with spermicide, IUD plus male condom+spermicide. Acceptable hormonal methods include: etonogestrel implants (i.e. Implanon, Norplan), normal and low dose combined oral pills, norelgestromin/ethinyl estradiol (EE) transdermal system, intravaginal device (i.e. EE and etonogestrel) or cerazette (desogestrel). All of these would need to be combined with male condom with spermicide

• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

• At least one lesion, not previously irradiated, that can be accurately measured at baseline as \>= 10 mm in the longest diameter (except lymph nodes which must have short axis \>= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements

• For inclusion in biomarker endpoint, patients must fulfill the following criterion:

⁃ Provision of informed consent for tumor biopsies \* If a patient declines to participate in tumor biopsies, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to that part