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

NCT02648711 | Terminated Phase 1

• 1 other identifier: CRLX101-102
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Solid Tumors

Keywords

solid tumors

Outcome Measures

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

  15 months

Secondary Outcomes (8)

• 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.

  15 months

• Pharmacokinetic Profile (PK) - Urine

  15 months

• Pharmacokinetic Profile (PK) - Plasma:CL

  15 months

• Pharmacokinetic Profile (PK) - Plasma:Vd

  15 months

• Pharmacokinetic Profile (PK) - Plasma:t1/2

  15 months

Study Arms (3)

CRLX101 alone

EXPERIMENTAL

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

CRLX101 in combination with bevacizumab

EXPERIMENTAL

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

CRLX101 in combination with mFOLFOX6

EXPERIMENTAL

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

CRLX101 DRUG

infusion CRLX101 weekly

Also known as: NLG207

CRLX101 alone; CRLX101 in combination with bevacizumab; CRLX101 in combination with mFOLFOX6

Bevacizumab DRUG

infusion weekly CRLX101 + bevacizumab biweekly

Also known as: Avastin

CRLX101 in combination with bevacizumab

mFOLFOX6 DRUG

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

Also known as: oxaliplatin, leucovorin, 5FU

CRLX101 in combination with mFOLFOX6

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (3)

START Midwest/Cancer & Hematology Centers of Western Michigan, PC

Grand Rapids, Michigan, 49503, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, 78229, United States

Location

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MeSH Terms

Interventions

IT-101; Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• NewLink Ge

  NewLink Genetics Inc

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: January 7, 2016
• Study Start: October 1, 2015
• Primary Completion: October 17, 2017
• Study Completion: May 7, 2018
• Last Updated: May 28, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)