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History of Changes for Study: NCT01434316
Veliparib and Dinaciclib With or Without Carboplatin in Treating Patients With Advanced Solid Tumors
Latest version (submitted June 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 13, 2011 None (earliest Version on record)
2 January 11, 2012 Recruitment Status, Study Status and Contacts/Locations
3 May 30, 2012 Study Status
4 August 26, 2012 Study Status and Eligibility
5 November 9, 2012 Recruitment Status, Outcome Measures, Sponsor/Collaborators, Contacts/Locations, Study Status, Arms and Interventions, Study Identification, Study Design, Conditions, Study Description, Oversight and Eligibility
6 November 19, 2012 Arms and Interventions, Study Status and Study Identification
7 December 12, 2012 Recruitment Status, Study Status and Contacts/Locations
8 February 1, 2013 Arms and Interventions, Outcome Measures, Study Status, Contacts/Locations, Eligibility and Oversight
9 August 1, 2013 Study Status, Study Description and Study Identification
10 September 27, 2013 Study Identification, Outcome Measures, Arms and Interventions, Study Status, Eligibility, Study Design and Study Description
11 February 10, 2014 Outcome Measures, Study Status, Contacts/Locations, Study Description and Study Identification
12 April 9, 2014 Study Status and Oversight
13 April 16, 2014 Study Status
14 May 19, 2014 Outcome Measures, Study Description, Arms and Interventions and Study Status
15 June 30, 2014 Study Status
16 July 28, 2014 Study Status
17 September 16, 2014 Study Status
18 September 23, 2014 Study Status
19 October 9, 2014 Study Status
20 November 15, 2014 Study Status
21 November 21, 2014 Arms and Interventions, Conditions and Study Status
22 November 25, 2014 Study Status
23 December 10, 2014 Study Status
24 December 15, 2014 Study Status
25 December 19, 2014 Study Status
26 January 23, 2015 Study Description, Eligibility, Outcome Measures, Arms and Interventions, Study Status and Study Identification
27 January 30, 2015 Study Status
28 February 2, 2015 Study Status
29 February 10, 2015 Study Status
30 March 2, 2015 Study Status
31 March 30, 2015 Conditions, Study Description and Study Status
32 April 6, 2015 Study Status
33 April 9, 2015 Arms and Interventions and Study Status
34 May 28, 2015 Study Status
35 June 26, 2015 Study Status
36 October 2, 2015 Study Status
37 November 3, 2015 Contacts/Locations, Outcome Measures, Arms and Interventions, Study Description, Study Identification, Eligibility, Study Design, Conditions and Study Status
38 November 11, 2015 Study Status
39 January 11, 2016 Contacts/Locations, Study Status and Study Identification
40 January 28, 2016 Study Status and Study Identification
41 March 1, 2016 Outcome Measures, Study Status, Contacts/Locations and Study Identification
42 April 11, 2016 Arms and Interventions and Study Status
43 June 17, 2016 Contacts/Locations, Study Status and Study Identification
44 July 20, 2016 Study Status
45 September 30, 2016 Oversight, Study Identification, Eligibility, Outcome Measures, Conditions, Study Description and Study Status
46 October 10, 2016 Study Status
47 January 19, 2017 Study Status
48 January 20, 2017 Study Status
49 January 23, 2017 Study Status
50 January 24, 2017 Study Status
51 January 31, 2017 Study Status
52 April 5, 2017 Outcome Measures, Study Status, Contacts/Locations, Eligibility, Arms and Interventions, Conditions, Study Description and Oversight
53 April 13, 2017 Study Status
54 May 18, 2017 Study Status
55 May 23, 2017 Study Status
56 June 26, 2017 Study Status
57 June 30, 2017 Study Status
58 November 1, 2017 Study Status, Outcome Measures, Arms and Interventions and Oversight
59 November 3, 2017 Study Status
60 December 7, 2017 Contacts/Locations and Study Status
61 December 11, 2017 Arms and Interventions and Study Status
62 February 5, 2018 Eligibility and Study Status
63 February 12, 2018 Study Status
64 March 2, 2018 Study Status
65 May 3, 2018 Eligibility and Study Status
66 May 11, 2018 Study Status
67 July 27, 2018 Study Status and Eligibility
68 July 30, 2018 Oversight and Study Status
69 November 26, 2018 Outcome Measures, Study Design and Study Status
70 December 3, 2018 Study Status
71 January 24, 2019 Eligibility and Study Status
72 February 1, 2019 Study Status
73 February 5, 2019 Contacts/Locations and Study Status
74 March 19, 2019 Outcome Measures, Eligibility, Arms and Interventions, Study Description and Study Status
75 March 27, 2019 Study Status
76 May 15, 2019 Outcome Measures, Arms and Interventions, Study Description and Study Status
77 May 23, 2019 Study Status
78 August 2, 2019 Contacts/Locations and Study Status
79 August 8, 2019 Contacts/Locations and Study Status
80 August 9, 2019 Study Status
81 October 4, 2019 Conditions and Study Status
82 November 18, 2019 Study Status
83 November 27, 2019 Study Status
84 December 9, 2019 Arms and Interventions and Study Status
85 January 22, 2020 Study Status and Arms and Interventions
86 February 3, 2020 Study Status
87 April 14, 2020 Arms and Interventions and Study Status
88 May 2, 2020 Arms and Interventions and Study Status
89 July 23, 2020 Study Status
90 January 15, 2021 Study Status
91 July 17, 2021 Study Status
92 December 21, 2021 Study Status
93 June 7, 2022 Arms and Interventions and Study Status
94 June 25, 2022 Study Status
95 June 28, 2022 Arms and Interventions and Study Status
Comparison Format:

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Study NCT01434316
Submitted Date:  September 13, 2011 (v1)

Open or close this module Study Identification
Unique Protocol ID: CDR0000710900
Brief Title: Veliparib and Dinaciclib With or Without Carboplatin in Treating Patients With Advanced Solid Tumors
Official Title: Phase 1 Trial of ABT-888 and SCH727965 Without or With Carboplatin in Patients With Advanced Solid Tumors
Secondary IDs: DFCI-11-144
Open or close this module Study Status
Record Verification: September 2011
Overall Status: Not yet recruiting
Study Start: January 2011
Primary Completion: October 2013 [Anticipated]
Study Completion:
First Submitted: September 13, 2011
First Submitted that
Met QC Criteria:
September 13, 2011
First Posted: September 14, 2011 [Estimate]
Last Update Submitted that
Met QC Criteria:
September 13, 2011
Last Update Posted: September 14, 2011 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Dana-Farber Cancer Institute
Responsible Party:
Collaborators: National Cancer Institute (NCI)
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:
Open or close this module Study Description
Brief Summary:

RATIONALE: Veliparib and dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving veliparib and dinaciclib with or without carboplatin may kill more tumor cells.

PURPOSE: This phase I trial studies the side effects and the best dose of veliparib and dinaciclib given together with or without carboplatin and to see how well they work in treating patients with advanced solid tumors.

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the safety and tolerability of veliparib (ABT-888) and dinaciclib (SCH727965) without or with carboplatin in patients with advanced solid tumors.
  • To determine the recommended phase 2 dose (RP2D) for ABT-888 in combination with SCH727965 without or with carboplatin, determined by evaluating the feasibility, safety, dose-limiting toxicities, and the maximally tolerated dose(s).

Secondary

  • To confirm the safety of the combination of ABT-888 and SCH727965 without or with carboplatin in patients with known BRCA1 or BRCA2 germline mutation.
  • To characterize the pharmacokinetic parameters of ABT-888 both alone and in combination with SCH727965 without or with carboplatin.
  • To assess the pharmacodynamic effects of ABT-888 in combination with SCH727965 without or with carboplatin, both in surrogate tissues and in tumor.
  • To assess preliminary antitumor activity of the ABT-888/SCH727965 and ABT- 888/SCH727965/carboplatin combinations in subjects with solid tumors.

OUTLINE: This is a dose-escalation study of veliparib and dinaciclib followed by an expanded BRCA-proficient and BRCA-deficient cohort study.

Part 1: Patients receive veliparib orally (PO) twice daily (BID) on days 1-28 and dinaciclib IV over 2 hours on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum-tolerated dose (MTD) is determined, part 2 of study is initiated.

Part 2: Patients receive veliparib and dinaciclib as patients in part 1. Patients also receive carboplatin IV over 60 minutes on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies, circulating tumor cells, and other correlative studies. Patients also undergo skin biopsy at baseline and on day 8 for correlative studies. Some patients undergo tumor biopsy (Tru-cut or core biopsy) on days 6 or 7 and 9 or 10 for correlative studies. Archived tumor tissue from diagnosis may also be obtained.

After completion of study treatment, patients are followed up every 3 months.

Open or close this module Conditions
Conditions: brca1 Mutation Carrier
brca2 Mutation Carrier
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
BRCA1 mutation carrier
BRCA2 mutation carrier
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model:
Number of Arms:
Masking: None (Open Label)
Enrollment: 98 [Anticipated]
Open or close this module Arms and Interventions
Intervention Details:
Drug: carboplatin
Drug: dinaciclib
Drug: veliparib
circulating tumor cell analysis
immunohistochemistry staining method
laboratory biomarker analysis
pharmacological study
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Recommended phase 2 dose of ABT-888/SCH727965 and ABT888/SCH727965/carboplatin
2. Dose-limiting toxicities according to NCI CTCAE v. 4.0
Secondary Outcome Measures:
1. Pharmacokinetics of ABT-888/SCH727965 and ABT888/SCH727965/carboplatin
2. Combined cdk2/cdk1/cdk9 inhibition and PARP inhibition in surrogate tissue and tumor
3. Level of DNA damage in surrogate tissue and tumor via assessment of γ-H2AX
4. Correlation between pharmacokinetic and pharmacodynamic findings
5. Association between pre-treatment expression of proteins involved in homologous recombination repair in archived tissue and tumor response
6. Anti-tumor activity of ABT-888/SCH727965 and ABT888/SCH727965/carboplatin
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of a solid tumor for which no standard or curative therapy exists or for which standard therapy is no longer effective
  • Measurable or evaluable disease
  • Eligible patients in the dose-escalation phases of the trial must agree to biopsies of normal skin, unless they undergo optional tumor biopsies and patients enrolled to the expanded cohorts must agree to tumor sampling
    • Patients on anticoagulation must be able to hold warfarin or low molecular weight heparin for a sufficient amount of time to make skin and tumor biopsies safe to perform
    • PT/INR and PTT should be ≤ 1.5 times the institutional upper limit of normal prior to performance of skin or tumor biopsies, with values re-checked after the eligibility screen as medically indicated
  • Patients enrolling in the BRCA-deficient cohort must have a documented BRCA1 or BRCA2 germline mutation
  • All patients must agree to provide an archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic correlative studies; however, patients are not considered ineligible if archival tumor is not available
  • Patients with known active brain metastases are excluded
    • Patients with a history of CNS metastases that have been treated must be stable with no symptoms for four weeks after completion of that treatment, with image documentation required

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • ECOG performance status ≤ 2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hgb > 9.0 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin < 1.5 mg/dL
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 times the institutional upper limit of normal (ULN) (for patients with known liver metastases, AST and ALT ≤ 5 times ULN)
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • PT/INR and PTT ≤ 1.5 times ULN
  • Women of childbearing 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
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib (ABT-888) and dinaciclib (SCH727965)
  • Patients must be able to swallow pills
  • Patients enrolling in Part 2 are excluded if they have a known allergy to platinum drugs (cisplatin or carboplatin)
  • No patients with other medical conditions judged by the investigator to be clinically relevant in the setting of this study, which may include active infectious processes, intractable emesis, or chronic diarrheal disease
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with prior seizure history who have experienced a seizure within the three months prior to enrollment are excluded
  • No patients with a known allergy to lidocaine

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients must not have received chemotherapy for 3 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of any prior chemotherapy
    • Patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to the initiation of study treatment
  • Prior exposure to approved receptor tyrosine kinase inhibitors is permitted
    • At least 5 half-lives must have elapsed since the completion of the kinase inhibitor and the initiation of study treatment
  • Patients must not have received any radiation within 3 weeks prior to the initiation of study treatment
    • Patients may not have areas of irradiated marrow exceeding 40% of bone marrow volume
  • Prior experimental (non-FDA approved) therapies and immunotherapies are allowed
    • Patients must not have received these therapies for 3 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
  • Prior exposure to veliparib (ABT-888) or other PARP inhibitors is permitted
  • Prior exposure to cyclin-dependent kinase inhibitors other than dinaciclib (SCH727965) is permitted
  • Patients must not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e., megestrol acetate, bisphosphonates)
    • Men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
  • No patients requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g., Neulasta®, Neupogen®)
  • No patients who have previously received SCH727965
  • Patients on a potent CYP3A4 inhibitor or CPY3A4 inducer who cannot be changed to another medication are excluded
Open or close this module Contacts/Locations
Study Officials: Geoffrey Shapiro, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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