Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
42

Inclusion Criteria

Biopsy must be of solid tumor tissue; ascites is not acceptable
Leukocytes ? 2,000/mcL
Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)
...
Biopsy must be of solid tumor tissue; ascites is not acceptable
Leukocytes ? 2,000/mcL
Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)
Ability to understand and the willingness to sign a written informed consent document
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.
For the expansion cohort patients must have ? 4 prior lines of chemotherapy
Platelets ? 100,000/mcL
Recurrent endometrial cancer (all histologies, including carcinosarcoma)
Absolute neutrophil count ? 1,500/mcL
Maintenance therapy is considered part of the preceding regimen if one or more of the same drugs are continued
Hormonal therapy is not considered anti-neoplastic therapy
PARP inhibitor was not the most recent treatment
Hemoglobin ? 9.0 g/dL
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
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
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
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
PARP inhibitor treatment was discontinued > 6 months before the first planned dose of rucaparib
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
Hormonal therapy does not count towards total lines of therapy
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)
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
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
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
For the dose escalation portion of the trial, patients with available therapies known to confer clinical benefit (platinum sensitive ovarian cancer) must be excluded
Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) ? 2.5 ? institutional upper limit of normal
Patients may have received unlimited prior treatment for the dose escalation part
Eastern cooperative oncology group (ECOG) performance status ? 1 and life expectancy > 12 weeks
Neoadjuvant and adjuvant chemotherapy are considered one regimen if they are a continuation of the same regimen with interval debulking surgery
Patients who have received prior taxanes, including weekly taxanes are allowed
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

Exclusion Criteria

History or evidence of thrombotic disorders within 6 months before first study treatment unless stable on anticoagulation for > 3 months
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with rucaparib and mirvetuximab soravtansine
Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)
...
History or evidence of thrombotic disorders within 6 months before first study treatment unless stable on anticoagulation for > 3 months
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with rucaparib and mirvetuximab soravtansine
Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)
History of leptomeningeal carcinomatosis
Interstitial lung disease (ILD)
Previous clinical diagnosis of non-infectious pneumonitis
Any known gastrointestinal disorder determined by the investigator that interferes with the absorption of rucaparib
For the dose expansion cohort patients with first-recurrence platinum-sensitive ovarian cancer must be excluded
Recent myocardial infarction (< 6 months)
Women who are breastfeeding
Required used of folate-containing supplements (e.g. folate deficiency)
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
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
History of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib, mirvetuximab soravtansine or monoclonal antibodies
Prior history of hypertensive crisis or hypertensive encephalopathy
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 multiple sclerosis or other demyelinating disease and/or Eaton-Lambert syndrome (para-neoplastic syndrome)
Patients with available therapies known to confer clinical benefit (platinum sensitive recurrent ovarian cancer) must be excluded from the dose escalation portion
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
Hemorrhagic or ischemic stroke < 6 months
Patients who are receiving any other investigational agents
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
Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Unstable angina pectoris
Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
Subjects with a known history of uncontrolled seizures
Active varicella zoster infection, cytomegalovirus infection, or history of tuberculosis
Uncontrolled cardiac arrhythmia
Active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C
Primary platinum refractory disease (disease progression on first platinum treatment or recurrence within 3 months of completing first platinum regimen)
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
History of neurological conditions that would confound assessment of treatment-emergent neuropathy
Active peptic ulcer disease or gastritis interfering 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)
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
Uncontrolled hypertension (? Common Terminology Criteria for Adverse Events [CTCAE] v4.03 grade 3)
Symptomatic/uncontrolled congestive heart failure (New York heart association > class II)

Summary

Conditions
  • BRCA1 Gene Mutation
  • BRCA2 Gene Mutation
  • Folate Receptor Alpha Positive
  • Platinum Resistant Ovarian Cancer
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Recurrent Uterine Carcinosarcoma
  • Recurrent Uterine Corpus Carcinoma
  • Recurrent Uterine Serous Carcinoma
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Only females

Description

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RPTD) of combination mirvetuximab soravtansine and rucaparib camsylate (rucaparib) in patients with recurrent endometrial, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. SECONDARY OBJECTIVES: I. To determine the...

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RPTD) of combination mirvetuximab soravtansine and rucaparib camsylate (rucaparib) in patients with recurrent endometrial, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of combination mirvetuximab soravtansine and rucaparib in study patients. II. To explore the objective antitumor activity (complete and partial response) of combination mirvetuximab soravtansine and rucaparib as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in the study population. III. To measure the progression free survival. IV. To evaluate the pharmacokinetics of mirvetuximab soravtansine and rucaparib in combination. EXPLORATORY OBJECTIVES: I. Explore additional biomarkers of response. II. Explore mutation characteristics and frequency with treatment response. III. Evaluate if companion diagnostics can be optimized by combining loss of heterozygosity (LOH) score and level of folate receptor a (FR-alpha) expression, and possible additional predictors of response. IV. Explore mechanisms of secondary resistance to treatment. OUTLINE: This is a dose escalation study. Participants receive mirvetuximab soravtansine intravenously (IV) on day 1 and rucaparib orally (PO) twice daily (BID) on days 1 through 21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days and then every 3 months for up to a year.

Inclusion Criteria

Biopsy must be of solid tumor tissue; ascites is not acceptable
Leukocytes ? 2,000/mcL
Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)
...
Biopsy must be of solid tumor tissue; ascites is not acceptable
Leukocytes ? 2,000/mcL
Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)
Ability to understand and the willingness to sign a written informed consent document
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.
For the expansion cohort patients must have ? 4 prior lines of chemotherapy
Platelets ? 100,000/mcL
Recurrent endometrial cancer (all histologies, including carcinosarcoma)
Absolute neutrophil count ? 1,500/mcL
Maintenance therapy is considered part of the preceding regimen if one or more of the same drugs are continued
Hormonal therapy is not considered anti-neoplastic therapy
PARP inhibitor was not the most recent treatment
Hemoglobin ? 9.0 g/dL
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
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
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
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
PARP inhibitor treatment was discontinued > 6 months before the first planned dose of rucaparib
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
Hormonal therapy does not count towards total lines of therapy
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)
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
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
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
For the dose escalation portion of the trial, patients with available therapies known to confer clinical benefit (platinum sensitive ovarian cancer) must be excluded
Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) ? 2.5 ? institutional upper limit of normal
Patients may have received unlimited prior treatment for the dose escalation part
Eastern cooperative oncology group (ECOG) performance status ? 1 and life expectancy > 12 weeks
Neoadjuvant and adjuvant chemotherapy are considered one regimen if they are a continuation of the same regimen with interval debulking surgery
Patients who have received prior taxanes, including weekly taxanes are allowed
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

Exclusion Criteria

History or evidence of thrombotic disorders within 6 months before first study treatment unless stable on anticoagulation for > 3 months
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with rucaparib and mirvetuximab soravtansine
Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)
...
History or evidence of thrombotic disorders within 6 months before first study treatment unless stable on anticoagulation for > 3 months
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with rucaparib and mirvetuximab soravtansine
Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)
History of leptomeningeal carcinomatosis
Interstitial lung disease (ILD)
Previous clinical diagnosis of non-infectious pneumonitis
Any known gastrointestinal disorder determined by the investigator that interferes with the absorption of rucaparib
For the dose expansion cohort patients with first-recurrence platinum-sensitive ovarian cancer must be excluded
Recent myocardial infarction (< 6 months)
Women who are breastfeeding
Required used of folate-containing supplements (e.g. folate deficiency)
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
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
History of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib, mirvetuximab soravtansine or monoclonal antibodies
Prior history of hypertensive crisis or hypertensive encephalopathy
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 multiple sclerosis or other demyelinating disease and/or Eaton-Lambert syndrome (para-neoplastic syndrome)
Patients with available therapies known to confer clinical benefit (platinum sensitive recurrent ovarian cancer) must be excluded from the dose escalation portion
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
Hemorrhagic or ischemic stroke < 6 months
Patients who are receiving any other investigational agents
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
Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Unstable angina pectoris
Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
Subjects with a known history of uncontrolled seizures
Active varicella zoster infection, cytomegalovirus infection, or history of tuberculosis
Uncontrolled cardiac arrhythmia
Active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C
Primary platinum refractory disease (disease progression on first platinum treatment or recurrence within 3 months of completing first platinum regimen)
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
History of neurological conditions that would confound assessment of treatment-emergent neuropathy
Active peptic ulcer disease or gastritis interfering 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)
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
Uncontrolled hypertension (? Common Terminology Criteria for Adverse Events [CTCAE] v4.03 grade 3)
Symptomatic/uncontrolled congestive heart failure (New York heart association > class II)

Locations

Columbus, Ohio, 43210
Columbus, Ohio, 43210

Tracking Information

NCT #
NCT03552471
Collaborators
  • ImmunoGen, Inc.
  • Clovis Oncology, Inc.
Investigators
  • Principal Investigator: Floor Backes, MD Ohio State University Comprehensive Cancer Center
  • Floor Backes, MD Ohio State University Comprehensive Cancer Center