A Study to Evaluate the Safety, Pharmacokinetics and Oral Bio Availability of Veliparib in Subjects With Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01853306
First received: March 22, 2013
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

This is a 3 part phase 1 study to evaluate the safety, pharmacokinetic and oral bioavailability of veliparib in subjects with solid tumors.


Condition Intervention Phase
Oncology
BRCA Mutated
High Grade Serous Ovarian Cancer
BRCA Mutated Breast Cancer
Drug: Veliparib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Oral Bioavailability of Veliparib Extended Release Formulations in Subjects With Solid Tumors

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Part 2 - Dose Escalation Cohort: Pharmacokinetic testing [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    Cmax, Tmax ,and AUC, and safety parameters

  • Part 1 - Pharmacokinetic profile [ Time Frame: Up to Day 6 ] [ Designated as safety issue: Yes ]
    The following pharmacokinetic parameters will be analyzed: Tmax, the terminal phase elimination rate constant (β), the natural logarithms of Cmax, AUCt and AUC∞.

  • Part 3 - Safety Expanded Cohort: Number of subjects with adverse events [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
  • Part 3 - Safety Expanded Cohort: Vital signs [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    Blood pressure, Heart rate

  • Part 3 - Safety Expanded Cohort: Laboratory tests [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    Hematology, Chemistry, Urinalysis


Secondary Outcome Measures:
  • The number of participants with adverse events who receive the extended release formulations of veliparib. [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: March 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Veliparib formulation A
veliparib formulation A
Drug: Veliparib
veliparib
Experimental: Veliparib formulation B
Veliparib formulation B
Drug: Veliparib
veliparib
Experimental: Veliparib formulation C
veliparib formulation C
Drug: Veliparib
veliparib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Part 1 and 2: Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Subjects must also 1) have a documented BRCA1 or BRCA2 mutation that is considered to be deleterious by the investigator, OR 2) have high grade serous ovarian, fallopian tube, or peritoneal cancer. Subjects with molecular features indicative of DNA repair defects (such as mutation in the Fanconi anemia pathway genes or methylation of the BRCA1 promoter) may be considered eligible for following discussion with the medical monitor. Part 3: Histologically or cytologically confirmed breast, ovarian, fallopian tube or primary peritoneal cancer that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Platinum-resistant ovarian cancer is not permitted. Subjects must also 1) have a documented BRCA1 or BRCA2 mutation that is considered to be deleterious by the investigator and 2) have received 3 or fewer regimens of cytotoxic chemotherapy in the metastatic setting and 3) have evaluable disease as defined by RECIST 1.1 or GCIC-CA-125 criteria.
  2. Subject must be at least 18 years of age.
  3. Completion of last anti-cancer therapy must be at least 28 days prior to study drug administration.
  4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
  5. Subject must have adequate hematologic, renal and hepatic function as follows:

    • Bone Marrow: Absolute neutrophil count ANC ≥ 1,500/mm3 (1.5 × 109/L); Platelets ≥ 100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.5 g/dL (1.4 mmol/L). Subjects with hemoglobin ≥ 9.5 g/dL (1.4 mmol/L) following transfusion are eligible;
    • Renal function: A calculated creatinine clearance value of ≥ 50 mL/min as determined by the Cockcroft Gault formula or a creatinine clearance value of ≥ 50 mL/min based on a 24-hour urine collection;
    • Hepatic function: AST and ALT ≤ 2.5 × the upper normal limit of institution's normal range. For subjects with liver metastases, AST and ALT ≤ 5 × the upper normal limit of institution's normal range;
    • Bilirubin: → 1.5 × the upper normal limit of institution's normal range.
  6. Women of childbearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy. Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

    • total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable;
    • vasectomized partner(s);
    • hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration;
    • intrauterine device (IUD);
    • Male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion if therapy.
  7. Subject must be capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study specific procedures.
  8. Must voluntarily sign and date each informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  1. The subject must not have received anti-tumor radiotherapy, biologic therapy, chemotherapy, or immunotherapy within 28 days or 5 half lives (whichever is shorter) of the start of Day 1. The subject must not have received hormonal therapy for anti-tumor purposes within 1 week prior to the start of Cycle 1 Day 1.
  2. Subject must not have known untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least one week prior to study drug administration).
  3. Clinically significant and uncontrolled major medical condition(s) including but not limited to:

    • Uncontrolled nausea/vomiting/diarrhea;
    • Active uncontrolled infection;
    • Symptomatic congestive heart failure;
    • Unstable angina pectoris or cardiac arrhythmia;
    • Psychiatric illness/social situation that would limit compliance with study requirements;
    • Focal or generalized seizure within the last 12 months.
  4. Any medical condition, which in the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities;
  5. Subject who has received strong inhibitors or inducers of CYP3A, 1A1, 2D6, or 2C19 within 3 days or five half-lives (whichever is shorter) prior to the first dose of veliparib (applicable to Part 1 only).
  6. Subject is pregnant or lactating.
  7. Subjects that have previously been treated with a veliparib.
  8. For Part 3, subject has ovarian cancer that was previously treated with platinum based chemotherapy resulting in progression free survival for < 6 months from the completion of treatment.
  9. For Part 3, subject has received 4 or more prior lines of cytotoxic chemotherapy for systemic disease.
  10. Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation within 28 days prior to study drug administration.
  11. The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured. Questions regarding the inclusion of individual subject should be directed to the Medical Monitor.
  12. History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
  13. Receipt of any investigational product within 28 days prior to study drug administration or 5 half-lives, whichever is longer.
  14. Current enrollment in another clinical study.
  15. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive veliparib.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01853306

Locations
United States, Arizona
Site Reference ID/Investigator# 89594
Scottsdale, Arizona, United States, 85258
United States, Michigan
Site Reference ID/Investigator# 89593
Detroit, Michigan, United States, 48201
United States, New Jersey
Site Reference ID/Investigator# 89834
Hackensack, New Jersey, United States, 07601
Site Reference ID/Investigator# 89595
New Brunswick, New Jersey, United States, 08903
United States, Utah
Site Reference ID/Investigator# 89596
Salt Lake City, Utah, United States, 84112
United States, Washington
Site Reference ID/Investigator# 97475
Seattle, Washington, United States, 98109
Sponsors and Collaborators
AbbVie
Investigators
Study Director: Mark McKee, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01853306     History of Changes
Other Study ID Numbers: M13-695
Study First Received: March 22, 2013
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Oncology
High grade serous ovarian cancer
BRCA mutated breast cancer
BRCA mutated

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on September 18, 2014