Solid NeoplasmPhase 1NCT01017640
Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors
A Phase 1 study testing Laboratory Biomarker Analysis, Mitomycin and Veliparib in people with Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Mitomycin and Veliparib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2009to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a histologically confirmed solid malignancy that is metastatic, or unresectable, or recurrent, for which no curative or standard of care exist, or this standard of care is no longer effective
- Tumors have been shown to be deficient for the FA pathway, based on Fanconi anemia triple stain immunofluorescence (FATSI) screening
- Patients will be consented to have their existing, or about to be obtained, paraffin embedded tumor tissue screened for FA deficiency; screening will be performed on an ongoing basis on the breast, thoracic, gastrointestinal (GI), Georgetown University (GU), and gynecologic (GYN) Ohio State University (OSU) clinics, anteceding and concurrently with the clinical trial; it will continue until the numbers of patients required for the clinical trial are identified and enrolled; based on the estimation from our preliminary data of 15 to 30% of patients, depending on the primary organ site, having tumors deficient for the FA pathway we will need to screen around 300 patients' samples to identify 40-50 patients; none of the eligibility criteria defined above or below will need to be met for the screening portion, since FA deficient patients identified by screening may meet eligibility criteria for the clinical trial at a later time; (e.g., patient is undergoing standard of care treatment at the time of the screening); separate written consents for screening and for the clinical trial will be obtained from patients
- Up to two chemotherapy regimens for metastatic disease are allowed; in addition, prior adjuvant/neo-adjuvant chemotherapy, hormonal therapy, molecular targeted therapy or estrogen receptor B (Erb) inhibitor treatments (e.g., erlotinib, Herceptin, sorafenib, sunitinib) will be allowed and will not count towards eligibility; at least 4 weeks must elapse since prior chemotherapy or radiation therapy (two weeks for erlotinib, hormonal therapy, or limited field palliative radiation to bone, brain, or radiosurgery), 6 weeks if the last regimen included nitrosoureas or mitomycin C; previous use of mitomycin C would be restricted to topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months
Show all 22Show fewer
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Hemoglobin >= 9 g/dL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limit
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Women of child-bearing potential and men 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 participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients should be able to swallow capsules
- EXPANSION COHORT:
- Diagnosis of colorectal malignancy
- Absence of Fanconi anemia, complementation group D2 (FANCD2) foci by FATSI screening
- Presence of biopsiable lesion by imaging
- Consent to a baseline (prior to treatment) tumor biopsy and for a repeat biopsy at the time of progression on the event that an antitumor response is demonstrated on the MMC-ABT-888 regimen
- Same eligibility as above, except that they will have no limitations related prior number of chemotherapy regimens given; patients could have received prior treatment with PARP inhibitors if used as single agent
Who cannot join
- Patients may not be receiving any other investigational agents
- Patients with known central nervous system (CNS) metastases (unless previously resected or irradiated and not clinically active); patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as ABT-888 or Mitomycin C
- 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; breastfeeding should be discontinued
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients with active seizure or a history of seizures
- Patients previously treated with PARP inhibitors; with the exception of patients enrolled on Arm 2 who may have had prior treatment with PARP inhibitors as monotherapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Georgetown Cancer Treatment Center
Georgetown, Kentucky, 40324
About this study
Official title: ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair
This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with mitomycin C may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To screen cancer patients across different histological sites to identify those with functional defects in the Fanconi anemia (FA) pathway in their tumors.
II. To establish the safety and practicality of treating patients with FA deficient tumors with the poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor ABT-888 (veliparib) as protracted monotherapy.
III. To establish the safety and practicality of treating patients with FA deficient tumors with the combination of mitomycin C (MMC) and ABT-888.
IV. To select a dose of ABT-888 protracted monotherapy and a dose-schedule of the combination of mitomycin C and ABT-888 in patients with FA deficient tumors for phase 2 trials.
SECONDARY OBJECTIVES:
- To evaluate for germ-line FA repair deficiency and BRCA mutations in peripheral blood mononuclear (PBMC) in patients receiving ABT-888 treatment.
II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2A histone family, member X (H2AX) in patients receiving mitomycin C with or without ABT-888 in order to assess any possible effect of ABT-888 in the cellular sensing and processing of mitomycin C-induced deoxyribonucleic acid (DNA) double strand breaks.
III. Quantify the number of patients with antitumor responses.
OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.
ARM I: Patients receive veliparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C intravenously (IV) over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
- Conditions
- Solid Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Mitomycin, Veliparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
MitomycinDrug
Also called Ametycine, MITO, MITO-C, Mito-Medac
Given IV
VeliparibDrug
Also called ABT-888, PARP-1 inhibitor ABT-888
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (veliparib) | Experimental | Patients receive veliparib PO BID in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Veliparib |
| Arm II (veliparib and mitomycin C) | Experimental | Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C IV over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Mitomycin; Drug: Veliparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ability to safely deliver the combination of mitomycin C and veliparib
Measured: Up to 12 weeks post-treatment
Ability to safely deliver veliparib in a continuous dose as monotherapy
Measured: Up to 12 weeks post-treatment
Feasibility of screening for FA deficiency across different tumor types, defined as adequate number of patients deficient on this pathway
Measured: Up to 12 weeks post-treatment
Selection of a dose schedule of the combination of mitomycin C and veliparib for phase II trials
Measured: Up to 12 weeks post-treatment
Selection of a dose schedule of veliparib monotherapy for phase II trials
Measured: Up to 12 weeks post-treatment
Secondary outcomes (4)
BRCA mutations
Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
Measured: Baseline
FancD2 foci formation in peripheral blood mononuclear cells
Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
Measured: Up to week 5
Foci produced by the histone variant gamma-H2AX
Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
Measured: Up to week 5
Tumor shrinkage as assessed by radiological means
Measured: Up to 12 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sameh Mikhail, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01017640
- Sponsor's protocol ID
- NCI-2012-01473
- Other IDs
- NCI-2012-01473, OSU-09100, OSU# 09100, 2009C0069, 09100, NCI 8472, CDR0000656393, OSU 09100
- Status last verified
- Jul 2016
- First submitted
- 19 Nov 2009
- Last updated
- 11 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair
- ClinicalTrials.gov ID
- NCT01017640
- Acronym / sponsor ID
- NCI-2012-01473
- Conditions
- Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2009
- Primary completion
- May 2016 (actual)
- First posted
- 20 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with mitomycin C may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To screen cancer patients across different histological sites to identify those with functional defects in the Fanconi anemia (FA) pathway in their tumors.
II. To establish the safety and practicality of treating patients with FA deficient tumors with the poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor ABT-888 (veliparib) as protracted monotherapy.
III. To establish the safety and practicality of treating patients with FA deficient tumors with the combination of mitomycin C (MMC) and ABT-888.
IV. To select a dose of ABT-888 protracted monotherapy and a dose-schedule of the combination of mitomycin C and ABT-888 in patients with FA deficient tumors for phase 2 trials.
SECONDARY OBJECTIVES:
- To evaluate for germ-line FA repair deficiency and BRCA mutations in peripheral blood mononuclear (PBMC) in patients receiving ABT-888 treatment.
II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2A histone family, member X (H2AX) in patients receiving mitomycin C with or without ABT-888 in order to assess any possible effect of ABT-888 in the cellular sensing and processing of mitomycin C-induced deoxyribonucleic acid (DNA) double strand breaks.
III. Quantify the number of patients with antitumor responses.
OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.
ARM I: Patients receive veliparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C intravenously (IV) over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (veliparib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: VeliparibPatients receive veliparib PO BID in the absence of disease progression or unacceptable toxicity. |
| Arm II (veliparib and mitomycin C) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Mitomycin, Drug: VeliparibPatients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C IV over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients must have a histologically confirmed solid malignancy that is metastatic, or unresectable, or recurrent, for which no curative or standard of care exist, or this standard of care is no longer effective
- Tumors have been shown to be deficient for the FA pathway, based on Fanconi anemia triple stain immunofluorescence (FATSI) screening
- Patients will be consented to have their existing, or about to be obtained, paraffin embedded tumor tissue screened for FA deficiency; screening will be performed on an ongoing basis on the breast, thoracic, gastrointestinal (GI), Georgetown University (GU), and gynecologic (GYN) Ohio State University (OSU) clinics, anteceding and concurrently with the clinical trial; it will continue until the numbers of patients required for the clinical trial are identified and enrolled; based on the estimation from our preliminary data of 15 to 30% of patients, depending on the primary organ site, having tumors deficient for the FA pathway we will need to screen around 300 patients' samples to identify 40-50 patients; none of the eligibility criteria defined above or below will need to be met for the screening portion, since FA deficient patients identified by screening may meet eligibility criteria for the clinical trial at a later time; (e.g., patient is undergoing standard of care treatment at the time of the screening); separate written consents for screening and for the clinical trial will be obtained from patients
- Up to two chemotherapy regimens for metastatic disease are allowed; in addition, prior adjuvant/neo-adjuvant chemotherapy, hormonal therapy, molecular targeted therapy or estrogen receptor B (Erb) inhibitor treatments (e.g., erlotinib, Herceptin, sorafenib, sunitinib) will be allowed and will not count towards eligibility; at least 4 weeks must elapse since prior chemotherapy or radiation therapy (two weeks for erlotinib, hormonal therapy, or limited field palliative radiation to bone, brain, or radiosurgery), 6 weeks if the last regimen included nitrosoureas or mitomycin C; previous use of mitomycin C would be restricted to topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Key exclusion criteria (8 listed)
- Patients may not be receiving any other investigational agents
- Patients with known central nervous system (CNS) metastases (unless previously resected or irradiated and not clinically active); patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as ABT-888 or Mitomycin C
- 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; breastfeeding should be discontinued
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (veliparib), Arm II (veliparib and mitomycin C) |
| MitomycinAlso: Ametycine, MITO, MITO-C, Mito-MedacGiven IV | Drug | Arm II (veliparib and mitomycin C) |
| VeliparibAlso: ABT-888, PARP-1 inhibitor ABT-888Given PO | Drug | Arm I (veliparib), Arm II (veliparib and mitomycin C) |
Primary outcome
Ability to safely deliver the combination of mitomycin C and veliparib
Time frame: Up to 12 weeks post-treatment
Ability to safely deliver veliparib in a continuous dose as monotherapy
Time frame: Up to 12 weeks post-treatment
Feasibility of screening for FA deficiency across different tumor types, defined as adequate number of patients deficient on this pathway
Time frame: Up to 12 weeks post-treatment
Selection of a dose schedule of the combination of mitomycin C and veliparib for phase II trials
Time frame: Up to 12 weeks post-treatment
Selection of a dose schedule of veliparib monotherapy for phase II trials
Time frame: Up to 12 weeks post-treatment
4 secondary outcomes
BRCA mutations
Time frame: Baseline
FancD2 foci formation in peripheral blood mononuclear cells
Time frame: Up to week 5
Foci produced by the histone variant gamma-H2AX
Time frame: Up to week 5
Tumor shrinkage as assessed by radiological means
Time frame: Up to 12 weeks post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sameh Mikhail principal investigator
Ohio State University Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis, Mitomycin and Veliparib in people with Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ability to safely deliver the combination of mitomycin C and veliparib (time frame: Up to 12 weeks post-treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2016.