| Eligibility |
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed:
- Recurrent endometrial cancer (all histologies, including carcinosarcoma)
- Recurrent ovarian, primary peritoneal (female only), or fallopian tube cancer
- all histologies except low grade serous or clear cell carcinoma unless the
patient has a known somatic or germline breast cancer (BRCA) mutation
disease that is metastatic and for which standard curative measures do not
exist or are no longer effective
- For the dose escalation portion of the trial, patients with available therapies known
to confer clinical benefit (platinum sensitive ovarian cancer) must be excluded
- For the dose expansion cohort, patients with recurrent endometrial cancer, recurrent
BRCA mutated ovarian cancer (except first-recurrence platinum sensitive ovarian
cancer), and platinum resistant ovarian cancer are eligible
- Patients must have confirmation of folate receptor-a (FR-alpha) positivity by
immunohistochemistry (IHC) (? 25% of tumor staining at ? 2 + intensity) on archival
tissue or recent biopsy.
- Patients must be willing and able to undergo tissue biopsy for research
- If tumor tissue obtained from the biopsy is deemed inadequate, and the patient is
unwilling or unable to have another biopsy, the patient may be considered for
enrollment if archival tumor tissue is provided and deemed of adequate quality;
this must occur prior to any treatment with rucaparib or mirvetuximab
soravtansine
- If biopsy is deemed unsafe to attempt or to perform, and if archival tumor tissue
is available and deemed of adequate quality, the patient may enroll on trial
- Biopsy must be of solid tumor tissue; ascites is not acceptable
- Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors
(RECIST) guideline (version 1.1)
- Prior therapy:
- Patients may have received unlimited prior treatment for the dose escalation part
- For the expansion cohort patients must have ? 4 prior lines of chemotherapy
- Hormonal therapy does not count towards total lines of therapy
- Maintenance therapy is considered part of the preceding regimen if one or more of
the same drugs are continued
- Neoadjuvant and adjuvant chemotherapy are considered one regimen if they are a
continuation of the same regimen with interval debulking surgery
- Prior treatment with folate receptor (FR) targeting investigational agents is allowed
for dose escalation provided that such treatment was not discontinued due to adverse
events; prior FR-targeting investigational agents are not allowed for patients in the
expansion cohort
- Patients with recurrent endometrial, ovarian, fallopian tube or primary peritoneal
cancer must have received at least one platinum-based chemotherapy regimen
- Patients who have received prior taxanes, including weekly taxanes are allowed
- Patients previously treated with a poly adenosine diphosphate (ADP) ribose polymerase
(PARP) inhibitor may be enrolled provided:
- PARP inhibitor was not the most recent treatment
- PARP inhibitor treatment was discontinued > 6 months before the first planned
dose of rucaparib
- Time from prior therapy:
- Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is
shorter (6 weeks for nitrosoureas or mitomycin C)
- Hormonal therapy is not considered anti-neoplastic therapy
- Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones)
completed at least four weeks, or focal radiation completed at least two weeks,
prior to starting study treatment
- Eastern cooperative oncology group (ECOG) performance status ? 1 and life expectancy >
12 weeks
- Leukocytes ? 2,000/mcL
- Absolute neutrophil count ? 1,500/mcL
- Platelets ? 100,000/mcL
- Hemoglobin ? 9.0 g/dL
- Total bilirubin ? 1.5 x upper limit of normal (ULN) (Patients with documented
diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/
alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) ? 2.5 ?
institutional upper limit of normal
- Creatinine ? 1.5 x upper limit of normal (ULN) OR creatinine clearance ? 50
mL/min/1.73 m^2 (using Cockroft Gault Formula) for patients with creatinine levels
above institutional normal
- Corrected QT (QTc) interval ? 470 msec on screening electrocardiogram (ECG)
- Major surgery must have been completed ? 4 weeks prior to starting treatment day 1;
patient must be sufficiently recovered and stable from surgery prior to treatment day
1
- Women of child-bearing potential 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; 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; patients must have a negative pregnancy test (urine
and/or serum) prior to enrollment
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients with available therapies known to confer clinical benefit (platinum sensitive
recurrent ovarian cancer) must be excluded from the dose escalation portion
- For the dose expansion cohort patients with first-recurrence platinum-sensitive
ovarian cancer must be excluded
- Patients who have had chemotherapy or radiotherapy within 4 weeks or five half-lives
whichever is shorter (6 weeks for nitrosoureas or mitomycin C) prior to entering the
study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual drug related toxicities > grade 1) except for alopecia and grade
2 fatigue
- Patients who are receiving any other investigational agents
- Primary platinum refractory disease (disease progression on first platinum treatment
or recurrence within 3 months of completing first platinum regimen)
- Patients with clear cell or low grade ovarian cancer unless the patient has a known
germline or somatic breast cancer (BRCA) mutation or a mutation in another homologous
recombination gene
- Any known gastrointestinal disorder determined by the investigator that interferes
with the absorption of rucaparib
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids; patients with treated
brain metastases are eligible as long as they completed prior brain radiation therapy
more than 14 days prior to first dose of study therapy, are not experiencing seizures
and are not receiving steroids for symptomatic brain metastases (for at least 7 days
prior to first dose of study treatment)
- History of leptomeningeal carcinomatosis
- Subjects with a known history of uncontrolled seizures
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to rucaparib, mirvetuximab soravtansine or monoclonal antibodies
- Uncontrolled inter-current illness including, but not limited to:
- Ongoing or active infection (requiring IV antibiotics within 2 weeks of study
enrollment)
- Symptomatic/uncontrolled congestive heart failure (New York heart association >
class II)
- Unstable angina pectoris
- Recent myocardial infarction (< 6 months)
- Uncontrolled cardiac arrhythmia
- Uncontrolled hypertension (? Common Terminology Criteria for Adverse Events
[CTCAE] v4.03 grade 3)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Hemorrhagic or ischemic stroke < 6 months
- Clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting
aneurysm), severe aortic stenosis clinically significant peripheral vascular
disease, or ? grade 3 cardiac toxicity following prior chemotherapy
- Interstitial lung disease (ILD)
- Active peptic ulcer disease or gastritis interfering with the absorption of
rucaparib
- Active bleeding diatheses including any subject known to have evidence of acute
or chronic hepatitis B, hepatitis C
- Active varicella zoster infection, cytomegalovirus infection, or history of
tuberculosis
- Psychiatric illness/social situations that would limit compliance with study
requirements or compromise the ability of the subject to give written informed
consent
- Active or chronic corneal disorder, including but not limited to the following:
Sjogren?s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal
transplantation, active herpetic keratitis, and also active ocular conditions
requiring on-going treatment/monitoring such as wet age-related macular degeneration
requiring intravitreal injections, active diabetic retinopathy with macular edema,
presence of papilledema, acquired monocular vision, and any preexisting active
conjunctival disease
- History of neurological conditions that would confound assessment of
treatment-emergent neuropathy
- History of multiple sclerosis or other demyelinating disease and/or Eaton-Lambert
syndrome (para-neoplastic syndrome)
- Previous clinical diagnosis of non-infectious pneumonitis
- History or evidence of thrombotic disorders within 6 months before first study
treatment unless stable on anticoagulation for > 3 months
- Required used of folate-containing supplements (e.g. folate deficiency)
- Has a known additional malignancy that is progressing or required active treatment
within 3 years of first dose of study treatment; exceptions include basal cell
carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
potentially curative therapy or other in situ cancers
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with rucaparib and mirvetuximab soravtansine
- Women who are breastfeeding
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
|
