This study is NOT currently recruiting participants.
Number
17-C-0012
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Fetuses;Children
Keywords
Top1 Inhibitor; PARP Inhibitor; Biomarkers
Recruitment Keyword(s)
None
Condition(s)
Solid Tumors
Investigational Drug(s)
Veliparib MM-398
Investigational Device(s)
Intervention(s)
Drug: Veliparib Drug: MM-398 Drug: Ferumoxytol
Supporting Site
National Cancer Institute
Advanced solid tumor cancer is usually treated with chemotherapy, radiotherapy, or surgery. But it often keeps growing. A targeted inhibitor of DNA repair enzyme called PARP in combination with chemotherapy has shown promise in laboratory studies. However, such combinations have proven to be too toxic in clinical trials to date. Researchers want to test if MM 398, a novel formulation of chemotherapy might be more tolerable than conventional chemotherapy in such combinations.
Objective:
To test the safety and tolerability of the combination of the study drugs MM-398 and veliparib.
Eligibility:
People ages 18 and older with advanced solid tumor cancer
Design:
Participants will be screened with:
Medication and supplement list
Medical history
Physical exam
Blood tests
Heart test
Participants will get the study drugs in 28-day cycles.
They will get MM-398 by IV for an hour and a half on days 1 and 15.
They will take a Veliparib capsule twice daily over several days.
Participants will complete a pill diary to bring to each visit.
Participants may have:
A scan 2 6 days before starting the study drugs. They are injected with a dye shortly after this scan. They have another scan 24 hours later.
About 12 hairs collected on several days of cycle 1.
Blood collected on several days of cycle 1.
Biopsies on days 5 and 19 of cycle 1. A hollow needle removes a small piece of tissue. A CT scan or ultrasound is used for guidance. The needle takes 3 6 samples.
Biobanking: Researchers store a biopsy sample and related health data for medical research.
Participants will continue treatment until their cancer gets worse or they can no longer tolerate side effects. After they stop treatment, their condition and side effects will be followed for 4 weeks.
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INCLUSION CRITERIA: - Patients must have pathologically confirmed diagnosis of a solid tumor cancer for which there is no known standard therapy capable of extending life expectancy. - Prior PARP inhibitor therapy is allowed. Patients with ovarian cancer and a BRCA mutation should have had prior treatment with olaparib per guidelines for standard of care treatment. -Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of veliparib in combination with MM-398 in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. -ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60). -Patients must have normal organ and marrow function measured within 28 days prior to administration of ABT-888 as defined below: --Hemoglobin greater than or equal to 10 g/dL with no blood transfusion in the past 28 days --leukocytes greater than or equal to 3,000/mcL --absolute neutrophil count greater than or equal to 1,500/mcL without the use of hematopoietic growth factors --platelets greater than or equal to 100,000/mcL --total bilirubin below institutional ULN --AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal (less than or equal to 5 times ULN is acceptable if liver metastases are present) --creatinine less than or equal to 1.5 times ULN OR --creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal. -Based on animal data, MM-398 (ONIVYDE (Trademark)) and Veliparib causes embryo toxicity and teratogenicity; thus, women of childbearing potential and male patients should use effective contraception during treatment with MM-398 and for 90 days following the final dose of Veliparib and MM-398 for both female and male patients. 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. -Ability to understand and the willingness to sign a written informed consent document. -Imaging Correlative Study A. Patients will be eligible to participate in the optional FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria: --Evidence of iron overload as determined by: --Fasting transferrin saturation of >45% and/or --Serum ferritin levels >1000 ng/ml B. A history of allergic reactions to any of the following: --compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection --any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations) --multiple drugs -Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI). EXCLUSION CRITERIA: -Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those whose adverse events have not resolved to grade 1 or less (except alopecia) from agents administered more than 4 weeks earlier.. Patients must have completed prior biological therapies and/or targeted therapies greater than or equal to 2 weeks prior to study enrollment. Patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (i.e. radiation to >25% of bone marrow) -Patients who are receiving any other investigational agents. -Subjects with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, subjects who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for at least 3 months may be enrolled. -History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib and MM-398. If patients have a history of allergic reactions to compounds resembling MM-398, they will be excluded from participating in the FMX MRI study, if applicable. -Patients who have severe hypersensitivity to irinotecan HCl. -Patients with known and confirmed diagnosis of Interstitial Lung Disease (IDL). -Clinically significant GI disorders, including history of small bowel obstruction unless the obstruction was a surgically treated remote episode. -Patient is unable to swallow or keep down oral medication. -Patients at the NCI site and other selected centers who are willing to undergo an optional pre-treatment ferumoxytol MRI must not have evidence of iron overload, a known hypersensitivity to ferumoxytol or any other IV iron product, a documented history of multiple drug allergies, or those for whom MRI is otherwise contraindicated, including claustrophobia or anxiety related to undergoing MRI. This exclusion criterion applies only to patients enrolling at NCI and other selected sites. Of note, the PI will allow other centers to offer FMX MRI scans if the site in question is willing and the site PI can identify the necessary resources and expertise at their center. -Active infection -Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. -Pregnant women are excluded from this study because veliparib, MM-398 and ferumoxytol are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with veliparib, MM-398 and/or ferumoxytol breastfeeding should be discontinued if the mother is treated with any of these agents. These potential risks may also apply to other agents used in this study. -HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with veliparib, MM-398 and/or ferumoxytol. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. -Patients who need chronic use of medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. -Veliparib has a potential seizure risk, therefore patients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months). -Patients wit treatment-related AML (t-AML)/MDS or with features suggestive of AML/MDS -Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
- Patients must have pathologically confirmed diagnosis of a solid tumor cancer for which there is no known standard therapy capable of extending life expectancy.
- Prior PARP inhibitor therapy is allowed. Patients with ovarian cancer and a BRCA mutation should have had prior treatment with olaparib per guidelines for standard of care treatment.
-Age greater than or equal to 18 years.
Because no dosing or adverse event data are currently available on the use of veliparib in combination with MM-398 in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
-ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60).
-Patients must have normal organ and marrow function measured within 28 days prior to administration of ABT-888 as defined below:
--Hemoglobin greater than or equal to 10 g/dL with no blood transfusion in the past 28 days
--leukocytes greater than or equal to 3,000/mcL
--absolute neutrophil count greater than or equal to 1,500/mcL without the use of hematopoietic growth factors
--platelets greater than or equal to 100,000/mcL
--total bilirubin below institutional ULN
--AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal (less than or equal to 5 times ULN is acceptable if liver metastases are present)
--creatinine less than or equal to 1.5 times ULN
OR
--creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
-Based on animal data, MM-398 (ONIVYDE (Trademark)) and Veliparib causes embryo toxicity and teratogenicity; thus, women of childbearing potential and male patients should use effective contraception during treatment with MM-398 and for 90 days following the final dose of Veliparib and MM-398 for both female and male patients. 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.
-Ability to understand and the willingness to sign a written informed consent document.
-Imaging Correlative Study
A. Patients will be eligible to participate in the optional FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria:
--Evidence of iron overload as determined by:
--Fasting transferrin saturation of >45% and/or
--Serum ferritin levels >1000 ng/ml
B. A history of allergic reactions to any of the following:
--compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection
--any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)
--multiple drugs
-Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI).
EXCLUSION CRITERIA:
-Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those whose adverse events have not resolved to grade 1 or less (except alopecia) from agents administered more than 4 weeks earlier.. Patients must have completed prior biological therapies and/or targeted therapies greater than or equal to 2 weeks prior to study enrollment. Patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (i.e. radiation to >25% of bone marrow)
-Patients who are receiving any other investigational agents.
-Subjects with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, subjects who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for at least 3 months may be enrolled.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib and MM-398. If patients have a history of allergic reactions to compounds resembling MM-398, they will be excluded from participating in the FMX MRI study, if applicable.
-Patients who have severe hypersensitivity to irinotecan HCl.
-Patients with known and confirmed diagnosis of Interstitial Lung Disease (IDL).
-Clinically significant GI disorders, including history of small bowel obstruction unless the obstruction was a surgically treated remote episode.
-Patient is unable to swallow or keep down oral medication.
-Patients at the NCI site and other selected centers who are willing to undergo an optional pre-treatment ferumoxytol MRI must not have evidence of iron overload, a known hypersensitivity to ferumoxytol or any other IV iron product, a documented history of multiple drug allergies, or those for whom MRI is otherwise contraindicated, including claustrophobia or anxiety related to undergoing MRI. This exclusion criterion applies only to patients enrolling at NCI and other selected sites. Of note, the PI will allow other centers to offer FMX MRI scans if the site in question is willing and the site PI can identify the necessary resources and expertise at their center.
-Active infection
-Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-Pregnant women are excluded from this study because veliparib, MM-398 and ferumoxytol are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with veliparib, MM-398 and/or ferumoxytol breastfeeding should be discontinued if the mother is treated with any of these agents. These potential risks may also apply to other agents used in this study.
-HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with veliparib, MM-398 and/or ferumoxytol. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
-Patients who need chronic use of medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible.
-Veliparib has a potential seizure risk, therefore patients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months).
-Patients wit treatment-related AML (t-AML)/MDS or with features suggestive of AML/MDS
-Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
Principal Investigator
Referral Contact
For more information: