AzTrials
AzTrials

Adult Solid NeoplasmPhase 1NCT01264432

Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis, Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer

A Phase 1 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Radiation Therapy in people with Adult Solid Neoplasm and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of veliparib when given together with radiation therapy in treating patients with advanced solid malignancies (abnormal cells divide without control and can invade nearby tissues) with peritoneal carcinomatosis, epithelial ovarian, fallopian, or primary… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Quality-of-Life Assessment and Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
3 sitesin 2 countries
Study dates
1 Jan 2011to 15 Nov 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

  • Dose levels 1-4 must have histologically proven solid malignancy that is metastatic or unresectable with metastatic peritoneal carcinomatosis; as this entity may be difficult to image, peritoneal disease can be documented through other modalities such as operative notes, clinical notes/symptoms, etc as well as imaging
  • Dose levels 5 and 6 will be open only to patients with recurrent or persistent primary epithelial ovarian, fallopian or peritoneal cancers; at these dose levels, measurable disease in the abdominal cavity must be present but peritoneal carcinomatosis is not required for eligibility
  • Patients must have failed first line standard therapy or have no acceptable standard treatment options; for patients on dose levels 5 and 6, patients may be platinum sensitive, platinum resistant or platinum refractory
  • Ability to understand and the willingness to sign a written informed consent document
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Life expectancy of greater than 3 months
Show all 19Show fewer
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Calcium within normal limit (WNL)
  • No surgery, hormonal therapy or chemotherapy within four weeks; for dose levels 5 and 6, patients receiving mitomycin C or nitrosoureas must discontinue treatment 6 weeks prior to registration and any hormonal treatment directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
  • No previous abdominal radiation; if the patient has received previous pelvic radiation there should not be any overlap between the current and previous radiation fields
  • Toxicities of prior chemotherapy recovered to grade 1 or less except for stable grade 2 peripheral neuropathy
  • Negative pregnancy test if premenopausal; 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
  • Archival tumor sample collection with a tumor block is required for all enrolled patients when available; this will not be required for patients on dose levels 5 and 6; if no block can be released per institutional policy, 10 to 20 unstained slides may be substituted; slides should have a positive charge and a thickness of 3 to 5 microns; if the only tissue sample available is a fine needle aspirate (FNA), the patient will still be considered eligible
  • Patients with central nervous system (CNS) metastases to be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
  • For patients in dose levels 5 and 6, BRCA testing results, if previously performed, should be attained; if no BRCA testing has been performed, patients may be referred to a genetic counselor and will have detailed family history performed as part of the screening process

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are currently receiving any other investigational agents
  • Brain metastases: patients with treated and stable brain metastasis for 3 months, off steroids will be eligible
  • Patients who demonstrate any clinical evidence of bleeding
  • Patients who have demonstrated an inability to swallow oral medications
  • Patients who currently have an active gastrointestinal obstruction, have had a gastrointestinal obstruction within the last 30 days prior to enrollment and/or are actively requiring parenteral nutrition are excluded; patients who have had a history of any prior gastrointestinal obstruction requiring surgical intervention are also excluded
Show all 13Show fewer
  • Patients who have a known hypersensitivity to the components of the study drug, its analogs or drugs of a similar chemical or biologic composition
  • 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 if the mother is treated with veliparib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients who have uncontrolled ascites
  • Patients with active seizures or a history of seizure are not eligible
  • Patients previously treated with poly (ADP-ribose) polymerase 1 (PARP) inhibitors

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I Study of Veliparib (ABT-888) in Combination With Low-Dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis With Two Additional Dose Levels in Patients With Epithelial Ovarian, Fallopian or Primary Peritoneal Cancers and Intra-Abdominal Disease

This phase I trial studies the side effects and best dose of veliparib when given together with radiation therapy in treating patients with advanced solid malignancies (abnormal cells divide without control and can invade nearby tissues) with peritoneal carcinomatosis, epithelial ovarian, fallopian, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Giving veliparib with radiation therapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerable dose of veliparib in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with peritoneal carcinomatosis from advanced solid malignancies. At dose levels 5 and 6: to determine the maximum tolerable dose of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.

II. Determine the safety and toxicity of the combination of veliparib in conjunction with LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies; at dose levels 5 and 6: to determine the safety and toxicity of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.

SECONDARY OBJECTIVES:

  1. Assess clinical activity of veliparib plus LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies as assessed by response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. At dose levels 5 and 6: to assess the clinical activity of veliparib plus LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancer and intraabdominal disease as assessed by response rate by RECIST 1.1 criteria.

II. Evaluate if microsatellite instability or baseline levels of various deoxyribonucleic acid (DNA) repair proteins (excision repair cross-complementing 1 [ERCC1], x-ray repair complementing defective repair in Chinese hamster cells 1 [XRCC1], breast cancer 1, early onset [BRCA1], breast cancer 2, early onset [BRCA2], poly [adenosine diphosphate (ADP)-ribosyl]ation [PAR]) correlate with clinical activity of this regimen.

III. Evaluate changes in quality of life for patients treated with this regimen by serial measurements using the Quality of Life Questionnaire Core-30 (QLQC-30) standardized questionnaire.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive veliparib orally (PO) twice daily (BID) on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Being tested
Laboratory Biomarker Analysis, Quality-of-Life Assessment, Radiation Therapy, Veliparib
Medical subject headings
Peritoneal Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation

    Undergo LDFWAR

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01264432
Study groupRoleWhat they receive
Treatment (veliparib, LDRWAR)ExperimentalPatients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Reported with exact binomial proportions and 95% confidence intervals.

    Measured: 28 days

Secondary outcomes (5)

  1. Changes in quality of life, assessed using the QLQC-30 standardized questionnaire

    The change in score will be evaluated with a paired t-test. Subscale scores of the quality of life questionnaire will be similarly analyzed.

    Measured: From baseline to 4 years

  2. Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria

    Reported descriptively.

    Measured: Up to 4 years

  3. Microsatellite instability (MSI)

    MSI will be correlated with response using a Fisher exact test and correlated with progression-free survival (PFS) using the log rank test and Kaplan-Meier curves. The effect of MSI on response and PFS, adjusting for other covariates, will be assessed using logistic regression and the Cox proportional hazards model.

    Measured: Baseline

  4. Presence of DNA repair proteins

    The presence of ERCC1, XRCC1, BRCA1, BRCA2, and PAR will be categorized by the level of staining: none, mild or strong. These data will be correlated with response and toxicity using the Cochran-Armitage trend test and logistic regression modeling.

    Measured: Baseline

  5. Proportion of toxicities of the combination of veliparib and LDRWAR as graded by the NCI CTCAE version 4.0

    Reported by type and grade with exact binomial proportions and 95% confidence intervals.

    Measured: Up to 4 weeks after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2010 (estimated)
  2. Study start1 Jan 2011
  3. Primary completion15 Nov 2016
  4. Study completion15 Nov 2016

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01264432
Sponsor's protocol ID
NCI-2012-02913
Other IDs
NCI-2012-02913, NA_00043143, J1097, NA_00043143, J1097, CDR0000691881, 8813, 8813, P30CA006973
Status last verified
Nov 2017
First submitted
20 Dec 2010
Last updated
21 Nov 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Radiation Therapy in people with Adult Solid Neoplasm and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 3 sites in 2 countries.

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 19 inclusion and 13 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 21 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Canada. 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?

Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01264432.

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 21 Nov 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in