A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma

NCT00804908 | Completed Phase 2 Results DMC

• 2 other identifiers: M10-4402008-004941-27
• Study Type: interventional
• Target: 346
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy of ABT-888 in combination with temozolomide versus temozolomide alone in subjects with metastatic melanoma.

Conditions

Melanoma; Metastatic Melanoma; Skin Cancer

Keywords

Temozolomide; Skin cancer; Melanoma; Metastatic Melanoma; ABT-888; MM

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS): Time to Event

  PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided.

  Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Secondary Outcomes (7)

• Overall Survival (OS): Time to Event

  Per protocol, survival follow-up information was to be obtained every 3 months for up to 18 months after the final visit for the subject. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

• 12-Month Overall Survival (OS) Rate

  Per protocol, survival was to be assessed every 4 weeks or as needed after participant is registered as off-study for up to 18 months. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

• 6-month Progression-Free Survival Rate

  Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

• Objective Response Rate

  Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

• Time to Disease Progression

  Every Cycle (28 Days), until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Study Arms (3)

Placebo for ABT-888 BID + TMZ QD

PLACEBO COMPARATOR

Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Drug: temozolomide; Other: Placebo

ABT-888 20 mg BID + TMZ QD

ACTIVE COMPARATOR

ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Drug: temozolomide; Drug: ABT-888

ABT-888 40 mg BID + TMZ QD

ACTIVE COMPARATOR

ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Drug: temozolomide; Drug: ABT-888

Interventions

temozolomide DRUG

temozolomide capsule administered orally once daily for 5 days every 28 days

Also known as: Temodar, Temodal

ABT-888 20 mg BID + TMZ QD; ABT-888 40 mg BID + TMZ QD; Placebo for ABT-888 BID + TMZ QD

ABT-888 DRUG

ABT-888 capsule administered orally twice daily for 7 days every 28 days

Also known as: veliparib

ABT-888 20 mg BID + TMZ QD; ABT-888 40 mg BID + TMZ QD

Placebo OTHER

Placebo for ABT-888 capsule administered orally twice daily for 7 days every 28 days

Placebo for ABT-888 BID + TMZ QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically (or cytologically) confirmed metastatic melanoma.
• Unresectable Stage III or Stage IV metastatic melanoma.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Subjects with no history of brain metastases demonstrated by a baseline MRI, or subjects with a history of previously treated brain metastases who have history of operable/SRS treatable brain metastases and completed surgical resection/stereotactic radiosurgery with or without adjuvant whole brain radiation at least 28 days prior to Day 1; have baseline MRI that shows no evidence of active intercranial disease; have discontinued taking medications for symptom management of brain metastases at least 7 days prior to Day 1
• days since prior anti-cancer therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
• Adequate hematologic, renal and hepatic function.
• Partial Thromboplastin Time (PTT) is \<= 1.5 x upper normal limit of institution's normal range and international normalized ratio (INR) \< 1.5.
• Subject's with significant fluid retention may be allowed at the discretion of the investigator.
• Life expectancy \> 12 weeks.
• Females must not be pregnant.
• Voluntarily signed informed consent.

You may not qualify if:

• Lactate Dehydrogenase (LDH) \> 2 x Upper Limit of Normal (ULN).
• Ocular malignant melanoma.
• History of central nervous system metastases or leptomeningeal disease.
• Prior treatment with Dacarbazine (DTIC) or Temozolomide (TMZ).
• Prior DNA damaging agents or cytotoxic chemotherapy.
• Prior Whole Brain Radiation Therapy (with exceptions).
• Received an investigational agent within 28 days of study.
• History of seizure disorder and/or taking medication for seizure disorder.
• Active malignancy within the past 5 years, except cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
• Medical condition that would cause a high risk for toxicities.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (1)

• Middleton MR, Friedlander P, Hamid O, Daud A, Plummer R, Falotico N, Chyla B, Jiang F, McKeegan E, Mostafa NM, Zhu M, Qian J, McKee M, Luo Y, Giranda VL, McArthur GA. Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma. Ann Oncol. 2015 Oct;26(10):2173-9. doi: 10.1093/annonc/mdv308. Epub 2015 Jul 22.

  PMID: 26202595 RESULT

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Temozolomide; veliparib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Information
• Organization: AbbVie

800-633-9110

Study Officials

• AbbVie Inc

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2008
• First Posted: December 9, 2008
• Study Start: February 1, 2009
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 6, 2018
• Results First Posted: March 3, 2017

Record last verified: 2017-03