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TerminatedNCT02648711Updated May 28, 2020

Alternative Dosing for CRLX101(NLG207) Alone, With Avastin and With mFOLFOX6 in Advanced Solid Tumors

A Phase 1 interventional study of CRLX101 and Bevacizumab in Solid Tumors, sponsored by NewLink Genetics Corporation. Terminated at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-05-28.

Sponsored by NewLink Genetics Corporation · Phase 1, Interventional, and Treatment

Why this study was terminated
Company decision
Phase
Phase 1
Study type
Interventional
Enrollment
41
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of weekly dosing of CRLX101 (both as monotherapy; (Schedule 1) and in combination with bevacizumab every 2 weeks (Schedule 2) and weekly with a 3 week on / 1 week off schedule in combination with mFOLFOX6 (Schedule 3) to affirm the dose for future clinical studies.

Read the detailed description

This is an open-label, dose escalation study. Subjects enrolled in Schedule 1 will receive weekly CRLX101 alone. The starting dose for Schedule 1 is 12 mg/m\^2 and the next dose level is 15 mg/m\^2 (or 10 mg/m\^2 if 12 mg/m\^2 is not well tolerated). No other dose levels in Schedule 1 will be explored.

Subjects enrolled in Schedule 2 will receive weekly CRLX101 in combination with bi-weekly bevacizumab (10 mg/kg) The starting dose for Schedule 2 is 12 mg/m\^ and the next dose is 15 mg/m\^2. No other dose levels in Schedule 2 will be explored

Subjects enrolled in Schedule 3 will receive weekly CRLX101 for 3 of every 4 weeks in combination with bi-weekly mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2 and 5FU (fluorouracil) 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous infusion). The starting dose for Schedule 3 is 12 mg/m\^2 and the next dose is 15 mg/m\^2.

In the absence of dose-limiting toxicities (DLTs) additional subjects may be enrolled (expansion cohort) at the same, intermediate or lower dose levels following consultation between the Investigator and Sponsor.

Enrollment of 6-8 subjects will occur in each cohort for all 3 Schedules.

The MTD is defined as the highest dose level at which fewer than 2 out of 6 subjects experience a DLT. RP2D will be selected based on overall tolerability data from all subjects treated at different dose cohorts in this study.

No intra-patient dose escalation is allowed.

Approximately 61 evaluable subjects are anticipated to be enrolled: 15 subjects in Schedule 1, 15 subjects in Schedule 2 and approximately 31 subjects are anticipated in Schedule 3 (approximately 16 in the dose escalation cohort and up to 15 in the expansion cohort).

The exact number of subjects is dependent on the actual number of subjects enrolled per cohort and the number of cohorts investigated.

02

Conditions studied

  • Solid Tumors

Browse trials for

Keywords

  • solid tumors
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 41 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

NewLink Genetics Corporation is the lead sponsor of 34 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria: (All Subjects)

  • Male or female adult subjects ≥18 years of age

  • Diagnosis of histologically or cytologically confirmed for:

    • For Schedule 1 and 2: advanced solid tumor malignancy that is refractory to standard therapy and/or for whom no further standard therapy is available
    • For Schedule 3: advanced/metastatic tumors for which mFOLFOX6 is appropriate, or advanced/metastatic tumors that may be sensitive to each component of mFOLFOX6 or sensitive to topoisomerase 1 inhibitors including pancreatic, colorectal, esophageal, gastric, bladder or ovarian cancer, triple-negative breast cancer, small cell lung cancer (SCLC), cholangiocarcinoma, among others
  • For Schedules 1 and 2: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2, For Schedule 3: ECOG Performance Status of 0 or 1
  • Life expectancy >12 weeks in the opinion of the Investigator

  • Subjects with acceptable pre-study* hematology and biochemistry labs ≤3 days prior to Week 1 Day 1 (W1D1) defined as:

    • absolute neutrophil count (ANC) ≥1.500 cells / µL (1.5 x 10°/L, without growth factor support
    • platelet count ≥100,000 cells/µL (100 x 10° cells/L), without growth factor support
    • hemoglobin ≥9 g/dL (90/g/L)
    • serum total bilirubin ≤1.5 upper limit of normal (ULN), unless Gilbert's disease
    • alanine transaminase (ALT) or aspartate transaminase (AST) ≤2.5 x ULN, (5 x ULN for subjects with liver metastases)

    • calculated or measured creatinine clearance ≥40 mL/min

      • NOTE: If screening hematology and biochemistry labs are performed ≤3 days prior to W1D1, additional pre-study labs do not need to be repeated to confirm eligibility. However, if screening hematology and biochemistry labs are performed greater than 3 days prior to W1D1, additional pre-study labs will need to be performed to confirm continued eligibility to ensure labs remain acceptable per protocol

  • Females of childbearing potential must agree to use two effective methods of contraception (or abstain completely from heterosexual intercourse) from the time of informed consent and for 30 days following last dose of study drug

    • NOTE: Females of childbearing potential are defined as women physically capable of becoming pregnant unless the female subject cannot have children due to surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal). Fertile males of childbearing potential are defined as men who are sexually capable to impregnate the female partner even if surgically sterilized (i.e., vasectomy).

      • highly effective methods of contraception include intra-uterine device (IUD) and hormonal contraception (oral, injectable, patches or implant)
      • effective methods of contraception include barrier methods (latex condom, diaphragm with spermicide, cervical cap, sponge)
      • when possible, subjects should be strongly encouraged to include at least one highly effective method of contraception
  • Male subjects must agree to use appropriate method of barrier contraception (latex condom with a spermicidal agent) or abstain completely from heterosexual intercourse fro the time of informed consent and for 120 days following last dose of study drug unless female partner absolutely cannot have children because of surgery or for other medical reasons
  • Negative urine pregnancy test
  • Ability to understand and willingness to sign a written informed consent form
  • Able to comply with study visit schedule and assessments

Exclusion Criteria: (All Subjects)

  • Subject has received:

    • chemotherapy or small molecular targeted therapy \<2 weeks prior to W1D1
    • approved antibody therapy \<5 half-lives from W1D1 (or 4 weeks since last therapy, whichever is the shortest)
    • local palliative radiation \<14 days from W1D1
    • invasive surgery requiring general anesthesia \<30 days from W1D1
    • chemotherapy with nitrosoureas or mitomycin C \<45 days from W1D1
  • Uncontrolled grade 2 or greater toxicity except alopecia related to any prior treatment (i.e., chemotherapy, targeted therapy, radiation or surgery) within 7 days prior to W1D1 unless approved by the Medical Monitor
  • Prolongation of QT/QTc interval (QTc interval >470) using the Fredericia method of QTc analysis
  • Women who are pregnant or nursing
  • Any known human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) or any concurrent infection requiring IV antibiotics
  • Any known clinically significant or concurrent acute liver disease, including viral hepatitis
  • Primary brain malignant tumors
  • Subjects with uncontrolled symptomatic central nervous system (CNS) involvement
  • Subjects requiring steroids at stable dose (>4 mg/day dexamethasone or equivalent) for at least 2 weeks
  • Uncontrolled hypertension >150/100 mmHg
  • Concurrent participation in any other investigational therapeutic study, unless non-interventional study and approved by Sponsor
  • History of stroke, deep venous thrombosis (DVT), transient ischemic attack (TIA), unstable angina, or myocardial infarction within 3 months prior to W1D1

  • Uncontrolled concurrent disease or illness including but not limited to:

    • symptomatic congestive heart failure (NYHA Class III or IV) per the NYHA Classification, unstable angina pectoris, clinically significant cardiac arrhythmia
    • unstable or untreated cardiac conditions or ejection fraction of \<50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
    • diabetes mellitus (i.e., fasting blood glucose >220 despite acceptable chronic diabetes therapy)
    • psychiatric illness that would limit compliance with study requirements, as determined by the Investigator
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for the study.
  • Known hypersensitivity to any component of CRLX101 or excipient or documented medical condition that would prohibit adequate pre-medication with antihistamine.
  • Presence of ≥Grade 1 cystitis

Exclusion Criteria for Subjects Enrolled in Schedule 2 Only

  • Minor surgical procedure, excluding placement of a vascular access device, within 24 hours prior to W1D1.
  • Cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV) per the NYHA Classification, angina pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months prior to therapy
  • Uncontrolled hypertension (defined as the presence of systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg on two separate occasions. Blood pressure must be controlled to a systolic blood pressure \<150 mmHg and/or to diastolic blood pressure \<100 mmHg prior to study treatment), or any prior history of hypertensive crisis or hypertensive encephalopathy
  • Peripheral vascular disease >Grade 1
  • Known congenital long QT syndrome, history of torsades de pointes or ventricular tachycardia.
  • Known history of pulmonary hypertension or non-infectious interstitial pneumonitis.
  • History or evidence of thrombotic or hemorrhagic disorders: including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA), intracerebral hemorrhage or sub- arachnoid hemorrhage ≤ 6 months prior to W1D1
  • Chronic daily aspirin >325 mg/day or clopidogrel (>75 mg/day)
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization
  • Any of the following serious, non-healing conditions:wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either: urine dipstick ≥2+ (subjects discovered to have a ≥2+ proteinuria on dipstick urinalysis at baseline should undergo 24-hour urine collection and must demonstrate \<1g of protein in 24 hours to be eligible): 24-hour urine collection demonstrates >1g of protein in 24 hours
  • Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing). [Note: testing is not mandatory to be eligible for the study. However, if a subject is at risk for having undiagnosed hepatitis C virus (HCV) (due to history of injection drug use or due to geographic location for example), testing at screening should be considered]
  • Chronic treatment with corticosteroids (prednisone >12.5 mg/day or dexamethasone >2 mg/day excluding inhaled steroids

Exclusion Criteria for Subjects Enrolled in Schedule 3 Only

  • Known hypersensitivity to 5FU, oxaliplatin or other platinum agent, or to their excipients
  • Known dihydropyridine dehydrogenase (DPD) enzyme deficiency (testing not required)
  • Baseline peripheral neuropathy grade ≥ 2
  • Progressive disease within ≤ 6 months of completing an oxaliplatin containing adjuvant therapy
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
41 participants (actual)

Study arms

  • Experimental
    CRLX101 alone

    Subjects will receive weekly infusion of CRLX101 alone. Starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2 (or 10 mg/m\^2 if 12 mg/m\^2 is not well tolerated. No other dose levels will be explored.

    Drug: CRLX101

  • Experimental
    CRLX101 in combination with bevacizumab

    Subjects receive weekly infusion of CRLX101 in combination with bi-weekly bevacizumab (10 mg/kg. The starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2. No other dose levels will be explored.

    Drug: CRLX101 · Drug: Bevacizumab

  • Experimental
    CRLX101 in combination with mFOLFOX6

    Subjects receive weekly infusion of CRLX101 for 3 of every 4 weeks in combination with bi-weekly mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2 and 5FU 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous infusion). The starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2.

    Drug: CRLX101 · Drug: mFOLFOX6

Interventions

  • DrugCRLX101

    infusion CRLX101 weekly

    Also known as: NLG207

  • DrugBevacizumab

    infusion weekly CRLX101 + bevacizumab biweekly

    Also known as: Avastin

  • DrugmFOLFOX6

    infusion weekly CRLX101 for 3 or every 4 weeks and in combination with bi-weekly mFOLFOX6

    Also known as: oxaliplatin, leucovorin, 5FU

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D)

    To determine the maximum tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of CRLX101 when administered by intravenous (IV) infusion every week (QW) alone (Schedule 1), (QW) in combination with bevacizumab (Q2W) (Schedule 2) and weekly with a 3-week on / 1-week off schedule in combination with mFOLFOX6 (Q2W) (Schedule 3) in subjects with advanced solid tumor malignancies

    Time frame: 15 months

Secondary outcomes

  1. Safety and Tolerability (Weekly Dosing) determined by reported adverse events, serious adverse events, physical exam findings, vital sign measurements,12-lead ECG readings, clinical lab evaluations, and treatment discontinuation due to toxicity.

    Will be determined by reported AEs, SAEs, physical exam findings, vital sign measurements,12-lead ECG readings, clinical lab evaluations, and treatment discontinuation due to toxicity.

    Time frame: 15 months

  2. Pharmacokinetic Profile (PK) - Urine

    Urine samples will be collected to evaluate the urinary excretion of total and unconjugated drug before, during, and after infusion. PK parameters in urine will include the maximum concentration (Cmax), amount of drug in the urine, % of drug eliminated in the urine. PK parameters will be calculated using non-compartmental analysis. Actual sampling times will be used to calculate PK parameters in this study.

    Time frame: 15 months

  3. Pharmacokinetic Profile (PK) - Plasma:CL

    Plasma PK parameters will include clearance (CL) for both total and unconjugated drug.

    Time frame: 15 months

  4. Pharmacokinetic Profile (PK) - Plasma:Vd

    The plasma PK parameters will include volume of distribution (Vd)

    Time frame: 15 months

  5. Pharmacokinetic Profile (PK) - Plasma:t1/2

    Plasma PK parameters will include half-life (t1/2)

    Time frame: 15 months

  6. Pharmacokinetic Profile (PK) - Plasma:Cmax

    Plasma PK parameters will include maximum concentration (Cmax)

    Time frame: 15 months

  7. Pharmacokinetic Profile (PK) - Plasma:AUC

    Plasma PK parameters will include area under the concentration versus time curve (AUC)

    Time frame: 15 months

  8. Anti-tumor Activity

    To further explore preliminary signs of anti-tumor activity of CRLX101 when administered alone (Schedule 1) and in combination with bevacizumab (Schedule 2), and in combination with mFOLFOX6 (Schedule 3)

    Time frame: 15 months

07

Study locations

3 sites
  • START Midwest/Cancer & Hematology Centers of Western Michigan, PC
    Grand Rapids, Michigan 49503, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • South Texas Accelerated Research Therapeutics (START), LLC
    San Antonio, Texas 78229, United States
08

References and documents

Publications

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Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 28, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02648711
Lead sponsor
NewLink Genetics Corporation
Responsible party
Sponsor
First posted
Jan 7, 2016
Start date
Oct 2015
Primary completion
Oct 17, 2017
Completion
May 7, 2018
Last update
May 28, 2020

Study contacts

NewLink Ge
study chair · NewLink Genetics Inc

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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