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Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer (INVICTAN®-3)

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ClinicalTrials.gov Identifier: NCT02776683
Recruitment Status : Completed
First Posted : May 18, 2016
Results First Posted : November 21, 2019
Last Update Posted : November 21, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The objective of this trial is to evaluate the safety and tolerability of BI 695502 in combination with leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) and as maintenance therapy (when applicable). As well as to evaluate the following efficacy parameters: Progression-free survival (PFS), objective response rate (proportion of patients with complete response [CR] plus partial response [PR]), overall survival (OS), duration of response (DOR), time to progression (TTP).

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: BI 695502 Drug: Avastin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open-label, Multicenter, Multinational, Safety and Efficacy Phase IIIb Trial of BI 695502 Plus mFOLFOX6 in Patients With Previously Untreated Metastatic Colorectal Cancer
Actual Study Start Date : June 8, 2016
Actual Primary Completion Date : October 3, 2018
Actual Study Completion Date : October 3, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All patients Drug: BI 695502
Drug: Avastin



Primary Outcome Measures :
  1. Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment [ Time Frame: From baseline up to 18 weeks after the last dose of trial medication prior to the Switch Visit. Maximum duration of up to 32 treatment cycles + safety follow up (up to 82 weeks overall). ]

    The primary safety endpoint of the trial was patients with any of the following selected adverse events (AEs):

    • Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions),
    • Thromboembolic events (arterial or venous),
    • Gastrointestinal perforations,
    • Hypertension,
    • Proteinuria,
    • Pulmonary hemorrhage
    • All hemorrhages (including pulmonary hemorrhages)
    • Wound-healing complications/abscess/fistulas
    • Posterior reversible encephalopathy syndrome
    • Ovarian failure. All AEs with an onset between start of treatment and end of the residual effect period (REP), a period of 18 weeks after the last dose of trial medication were considered for the primary safety analysis. Confidence interval was calculated using Wilson score method.


Secondary Outcome Measures :
  1. Duration of Response (DOR) as Assessed by Central Imaging Review [ Time Frame: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks). ]
    DOR was the time from first documented Complete Response (CR) (CR is disappearance of all target lesions) or Partial Response (PR) (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) until time of progression as assessed by central imaging review per Response evaluation criteria in solid tumors (RECIST) 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. DOR was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

  2. Time to Progression (TTP) as Assessed by Central Imaging Review [ Time Frame: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks). ]
    TTP was defined as the time from first administration of trial medication to the date of tumor progression as assessed by central imaging review per RECIST 1.1 (RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.). TTP was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

  3. Objective Response (OR) Rate as Assessed by Central Imaging Review [ Time Frame: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks). ]

    OR rate was defined as the percentage of patients who achieved at least one visit response of CR (CR is disappearance of all target lesions) or PR (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) after the start of treatment. The response criteria evaluation was carried out according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Confidence interval was calculated using Wilson score method. The definition for OR (CR/PR) extends until disease progression/ death/ unacceptable toxicity/ end of the trial, whichever occurred earlier. However for "Duration of response" this censoring does not apply. Hence the apparent discrepancy.

    OR = CR + PR.


  4. Overall Survival (OS) Time [ Time Frame: From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall). ]
    OS was defined as the time from first administration of trial medication until death from any cause. OS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

  5. Progression-Free Survival (PFS) Time as Assessed by Central Imaging Review [ Time Frame: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks). ]
    PFS was defined as the time from first administration of trial medication until disease progression as assessed by central imaging review or death due to any cause. Disease progression was assessed according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. PFS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Males and females aged >=18 years (for Japan only: Age >=20 years at time of signing Informed Consent Form) with histologically confirmed metastatic colorectal cancer (mCRC).
  • Metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 (Leucovorin/5-Fluorouracil/Oxaliplatin) + bevacizumab.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Adequate hepatic, renal and bone marrow function.
  • Further inclusion criteria apply.

Exclusion criteria:

  • Prior systemic therapy for metastatic disease
  • Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular endothelial growth factor (VEGF) or VEGF receptors, including Avastin® or Avastin® biosimilar
  • Previous malignancy other than Colorectal cancer (CRC) in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix
  • Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 6 weeks prior to start of study treatment
  • Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy)
  • History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
  • A thrombotic or hemorrhagic event <=6 months prior to screening (includes hemoptysis, Gastrointestinal (GI) bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease)
  • Further exclusion criteria apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02776683


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Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Statistical Analysis Plan  [PDF] December 13, 2018
Study Protocol  [PDF] January 17, 2018


Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02776683     History of Changes
Other Study ID Numbers: 1302.3
2015-003718-25 ( EudraCT Number )
First Posted: May 18, 2016    Key Record Dates
Results First Posted: November 21, 2019
Last Update Posted: November 21, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors