Untreated Metastatic Colorectal CancerPhase 2NCT02305758
Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer
A Phase 2 study testing Veliparib, Modified FOLFIRI and FOLFIRI in people with Untreated Metastatic Colorectal Cancer, run by AbbVie.
Trial summary
This was a blinded, randomized, placebo-controlled Phase 2 multicenter study evaluating the efficacy and tolerability of veliparib plus irinotecan, fluorouracil, and leucovorin chemotherapy regimen (FOLFIRI) compared to placebo plus FOLFIRI in participants with previously untreated metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Untreated Metastatic Colorectal Cancer
- What is being tested?
- Veliparib, Modified FOLFIRI and FOLFIRI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- No sites listed yet
- Study dates
- 2 Dec 2014to 22 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
- At least 1 unresectable lesion on a CT (Computerized Tomography) scan that is measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
- ECOG (Eastern Cooperative Oncology Group) performance score of 0 or 1
- Adequate hematologic, renal and hepatic function
Who cannot join
- Prior anti-cancer treatment for metastatic colorectal cancer
- Prior exposure to PARP (poly ADP-ribose polymerase) inhibitors
- The last course of adjuvant or neoadjuvant chemotherapy must have ended > 12 months prior to Cycle 1 Day -2
- Any clinically significant and uncontrolled major medical condition
- Participant is pregnant or lactating
- Any medical condition, which in the opinion of the study Investigator, places the participant at an unacceptably high risk for toxicities
- For those receiving bevacizumab, standard medical exclusionary conditions apply
About this study
Official title: Randomized, Blinded, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer
This was a blinded, randomized, placebo-controlled Phase 2 multicenter study evaluating the efficacy and tolerability of veliparib plus irinotecan, fluorouracil, and leucovorin chemotherapy regimen (FOLFIRI) compared to placebo plus FOLFIRI in participants with previously untreated metastatic colorectal cancer. Participants could also have been treated with bevacizumab at the discretion of the Investigator.
Read the detailed description
Participants were randomized to one of 2 groups: veliparib plus FOLFIRI ± bevacizumab (veliparib group) or placebo plus FOLFIRI ± bevacizumab (placebo group), and stratified by planned use of bevacizumab (planned bevacizumab use compared to unplanned use of bevacizumab) and regions of the world (North America versus rest of world). In this study, the term FOLFIRI was used to describe both the standard regimen containing a fluorouracil bolus that was administered to participants randomized to the placebo arm, and a modified regimen with a saline bolus that was administered to participants randomized to the veliparib arm. One cycle of protocol therapy consisted of 14 days, defined as Day -2 through Day 12. Dosing of oral veliparib/placebo began 2 days prior to the start of FOLFIRI and continued twice a day for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab could be administered intravenously immediately preceding FOLFIRI. Study visits were conducted on Day 1 and Day 8 of the first and second cycles, then on Day 1 of each subsequent cycle. Participants were to continue protocol therapy and study visits until they met one of the defined discontinuation criteria. When the Investigator determined that a participant met the criteria for discontinuation, a final visit was conducted. Participants were to have had one follow-up visit approximately 30 days after the last dose of protocol therapy. Sites began collecting post-treatment and survival information 4 weeks after the last clinical assessment. Post-baseline radiographic tumor assessment was to be conducted every 8 weeks from Cycle 1, Day 1 (prior to the start of a new cycle) until radiographic progression.
- Conditions
- Untreated Metastatic Colorectal Cancer
- Being tested
- Veliparib, Placebo, Modified FOLFIRI, FOLFIRI, Bevacizumab
- Keywords
- PARP inhibitor, veliparib, metastatic colorectal cancer, ABT-888, first line, previously untreated, colorectal cancer, colon cancer, rectal cancer, FOLFIRI, fluorouracil, 5-FU, leucovorin, irinotecan
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VeliparibDrug
Also called ABT-888
200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days
PlaceboDrug
200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days
Modified FOLFIRIDrug
Irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) on Day 1 of each 14-day cycle
FOLFIRIDrug
Irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m^2 (up to 15-minute infusion) on Day 1 of each 14-day cycle
BevacizumabDrug
Also called Avastin
At the discretion of the Investigator, 5 mg/kg may be administered intravenously immediately preceding FOLFIRI dosing
Fluorouracil infusionDrug
Also called 5-FU
2400 mg/m^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Veliparib + modified FOLFIRI ± bevacizumab | Experimental | Dosing of oral veliparib (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Modified FOLFIRI was administered as irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle. Receives: Drug: Veliparib; Drug: Modified FOLFIRI; Drug: Bevacizumab; Drug: Fluorouracil infusion |
| Placebo + FOLFIRI ± bevacizumab | Placebo comparator | Dosing of oral placebo (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Standard FOLFIRI was administered as irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m^2 (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m^2 (46-hour continuous infusion ± 4 hours) on Day 1 of each 14-day cycle. Receives: Drug: Placebo; Drug: FOLFIRI; Drug: Bevacizumab; Drug: Fluorouracil infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS): Time to Event
PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not died as defined above, data were censored at the date of the participant's last evaluable disease progression assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the PFS distribution quartiles are provided.
Measured: Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.
Secondary outcomes (2)
Overall Survival (OS): Time to Event
Overall survival was defined as the number of days from the date that the participant was randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurred while the participant was still taking or had discontinued study drug. If a participant had not died, the data were censored at the date last known to be alive. The OS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the OS distribution quartiles are provided.
Measured: Survival information was to be collected 4 wks after the last study visit, continuing every 4 wks for 1 yr, then every 8 wks for up to 2 more yrs or until death. The maximum observed follow up duration at the overall survival analysis time was 914 days.
Objective Response Rate (ORR)
ORR was defined as the proportion of participants with a complete (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) for target lesions, assessed by computed tomography (CT). Complete response (CR) was defined as disappearance of all target lesions; partial response (PR) ≥30% decrease in the the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who underwent surgery, ORR was not evaluated after surgery.
Measured: Per protocol, post-baseline tumor assessment was conducted every 8 weeks from Cycle 1 Day 1 until radiographic progression. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2014 (estimated)
- Study start2 Dec 2014
- Primary completion22 Sep 2017
- Study completion22 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Untreated Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by AbbVieThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02305758
- Sponsor's protocol ID
- M14-217
- Other IDs
- 2014-002866-65, 2014
- Status last verified
- Nov 2018
- First submitted
- 1 Dec 2014
- Last updated
- 20 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Blinded, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02305758
- Acronym / sponsor ID
- M14-217
- Conditions
- Untreated Metastatic Colorectal Cancer
- Keywords
- PARP inhibitor, veliparib, metastatic colorectal cancer, ABT-888, first line, previously untreated, colorectal cancer, colon cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2014 (actual)
- Primary completion
- 22 Sep 2017 (actual)
- Study completion
- 22 Sep 2017 (actual)
- First posted
- 3 Dec 2014 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a blinded, randomized, placebo-controlled Phase 2 multicenter study evaluating the efficacy and tolerability of veliparib plus irinotecan, fluorouracil, and leucovorin chemotherapy regimen (FOLFIRI) compared to placebo plus FOLFIRI in participants with previously untreated metastatic colorectal cancer. Participants could also have been treated with bevacizumab at the discretion of the Investigator.
Detailed description
Participants were randomized to one of 2 groups: veliparib plus FOLFIRI ± bevacizumab (veliparib group) or placebo plus FOLFIRI ± bevacizumab (placebo group), and stratified by planned use of bevacizumab (planned bevacizumab use compared to unplanned use of bevacizumab) and regions of the world (North America versus rest of world). In this study, the term FOLFIRI was used to describe both the standard regimen containing a fluorouracil bolus that was administered to participants randomized to the placebo arm, and a modified regimen with a saline bolus that was administered to participants randomized to the veliparib arm. One cycle of protocol therapy consisted of 14 days, defined as Day -2 through Day 12. Dosing of oral veliparib/placebo began 2 days prior to the start of FOLFIRI and continued twice a day for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab could be administered intravenously immediately preceding FOLFIRI. Study visits were conducted on Day 1 and Day 8 of the first and second cycles, then on Day 1 of each subsequent cycle. Participants were to continue protocol therapy and study visits until they met one of the defined discontinuation criteria. When the Investigator determined that a participant met the criteria for discontinuation, a final visit was conducted. Participants were to have had one follow-up visit approximately 30 days after the last dose of protocol therapy. Sites began collecting post-treatment and survival information 4 weeks after the last clinical assessment. Post-baseline radiographic tumor assessment was to be conducted every 8 weeks from Cycle 1, Day 1 (prior to the start of a new cycle) until radiographic progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Veliparib + modified FOLFIRI ± bevacizumab | Experimental | Drug: Veliparib, Drug: Modified FOLFIRI, Drug: Bevacizumab, Drug: Fluorouracil infusionDosing of oral veliparib (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Modified FOLFIRI was administered as irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle. |
| Placebo + FOLFIRI ± bevacizumab | Placebo comparator | Drug: Placebo, Drug: FOLFIRI, Drug: Bevacizumab, Drug: Fluorouracil infusionDosing of oral placebo (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Standard FOLFIRI was administered as irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m^2 (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m^2 (46-hour continuous infusion ± 4 hours) on Day 1 of each 14-day cycle. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
- At least 1 unresectable lesion on a CT (Computerized Tomography) scan that is measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
- ECOG (Eastern Cooperative Oncology Group) performance score of 0 or 1
- Adequate hematologic, renal and hepatic function
Key exclusion criteria (7 listed)
- Prior anti-cancer treatment for metastatic colorectal cancer
- Prior exposure to PARP (poly ADP-ribose polymerase) inhibitors
- The last course of adjuvant or neoadjuvant chemotherapy must have ended > 12 months prior to Cycle 1 Day -2
- Any clinically significant and uncontrolled major medical condition
- Participant is pregnant or lactating
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 |
|---|---|---|
| VeliparibAlso: ABT-888200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days | Drug | Veliparib + modified FOLFIRI ± bevacizumab |
| Placebo200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days | Drug | Placebo + FOLFIRI ± bevacizumab |
| Modified FOLFIRIIrinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) on Day 1 of each 14-day cycle | Drug | Veliparib + modified FOLFIRI ± bevacizumab |
| FOLFIRIIrinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m^2 (up to 15-minute infusion) on Day 1 of each 14-day cycle | Drug | Placebo + FOLFIRI ± bevacizumab |
| BevacizumabAlso: AvastinAt the discretion of the Investigator, 5 mg/kg may be administered intravenously immediately preceding FOLFIRI dosing | Drug | Placebo + FOLFIRI ± bevacizumab, Veliparib + modified FOLFIRI ± bevacizumab |
| Fluorouracil infusionAlso: 5-FU2400 mg/m^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle | Drug | Placebo + FOLFIRI ± bevacizumab, Veliparib + modified FOLFIRI ± bevacizumab |
Primary outcome
Progression-Free Survival (PFS): Time to Event
Time frame: Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.
PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not died as defined above, data were censored at the date of the participant's last evaluable disease progression assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the PFS distribution quartiles are provided.
2 secondary outcomes
Overall Survival (OS): Time to Event
Time frame: Survival information was to be collected 4 wks after the last study visit, continuing every 4 wks for 1 yr, then every 8 wks for up to 2 more yrs or until death. The maximum observed follow up duration at the overall survival analysis time was 914 days.
Objective Response Rate (ORR)
Time frame: Per protocol, post-baseline tumor assessment was conducted every 8 weeks from Cycle 1 Day 1 until radiographic progression. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Untreated Metastatic Colorectal Cancer
Active, not recruitingPhase 3
A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
Neoplasms
Not yet recruitingPhase 2
Cemiplimab With Fianlimab for Resectable Non-Metastatic Colon Cancer
Colon Cancer
RecruitingPhase 2/3
A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Bevacizumab in Combination With Chemotherapy in Participants With Previously Untreated, Unresectable, or Metastatic Colorectal Cancer
Untreated, Unresectable, or Metastatic Colorectal Cancer
Active, not recruitingPhase 3
Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
Colorectal Adenocarcinoma
Active, not recruitingPhase 2
A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
Metastatic Colorectal Cancer
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.
AbbVie Inc. study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Veliparib, Modified FOLFIRI and FOLFIRI in people with Untreated Metastatic Colorectal Cancer, run by AbbVie.
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 4 inclusion and 7 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 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-Free Survival (PFS): Time to Event (time frame: Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.). 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 20 Nov 2018; AzTrials last refreshed its copy on 6 Nov 2026.