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Pancreatic CancerPhase 1NCT01803282

Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Chemotherapy in Participants With Advanced Solid Tumors

A Phase 1 study testing Andecaliximab, Gemcitabine and Nab-paclitaxel in people with Pancreatic Cancer and Non-small Cell Lung Cancer, run by Gilead Sciences at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of the study is to determine the maximum tolerated dose of andecaliximab monotherapy and to evaluate the safety and tolerability of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy. The study consists of 2 parts (Parts A and B). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Andecaliximab, Gemcitabine and Nab-paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
236 participants
Where
18 sitesUnited States
Study dates
29 Mar 2013to 23 Apr 2019
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
  • Part B: Pancreatic Adenocarcinoma
  • Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinoma
  • Part B: NSCLC
  • Stage IIIB with malignant pleural effusion/pleural seeding or stage IV histologically confirmed NSCLC
  • Absence of known epidermal growth factor receptor (EGFR) mutation
Show all 25Show fewer
  • Absence of known translocation or inversion events involving the ALK gene locus (resulting in EML4-ALK fusion)
  • Part B: Esophagogastric Adenocarcinoma:
  • Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapsed gastric adenocarcinoma
  • Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion)
  • Part B: First-Line Colorectal Cancer
  • Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
  • Radiographically measureable disease
  • No prior cytotoxic chemotherapy to treat their metastatic disease
  • Part B: Second-Line Colorectal Cancer
  • Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
  • Radiographically measureable disease
  • Received first-line combination therapy containing oxaliplatin and fluoropyrimidine with or without bevacizumab for metastatic disease with documented evidence of disease progression during or after treatment completion
  • Part B: Breast Cancer
  • Histologically or cytologically confirmed metastatic breast cancer
  • Radiographically measureable disease
  • Previous hormonal therapy for metastatic breast cancer or cytotoxic adjuvant chemotherapy is allowed
  • Treatment with weekly single-agent paclitaxel is appropriate in the opinion of the treating physician
  • HER-2 negative tumor (primary tumor or metastatic lesion)
  • Adequate organ function

Who cannot join

  • Pregnant or lactating
  • Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids
  • Myocardial infarction, symptomatic congestive heart failure, unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months
  • Anti-tumor therapy within 28 days of study drug dosing; concurrent use of hormone therapy for breast or prostate cancer is permitted
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Comprehensive Blood and Cancer Center

    Bakersfield, California, 93309

  • Alabama Oncology

    Birmingham, Alabama, 35243

  • UT Southwestern

    Dallas, Texas, 75390

  • San Diego Pacific Oncology and Hematology Associates, Inc.

    Encinitas, California, 92024

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Indiana University Health Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Greenville Health System, Institute for Translational Oncology Research

    Greenville, South Carolina, 29605

  • University of Southern California (USC)

    Los Angeles, California, 90033

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt

    Nashville, Tennessee, 37232

  • Cornell University

    New York, New York, 10021

  • University of Utah

    Salt Lake City, Utah, 84112

  • California Pacific Medical Center

    San Francisco, California, 94115

  • UCLA Medical Center

    Santa Monica, California, 90404

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Pinnacle Oncology Hematology

    Scottsdale, Arizona, 85258

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

Other trials in United States

About this study

Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors

The primary objective of the study is to determine the maximum tolerated dose of andecaliximab monotherapy and to evaluate the safety and tolerability of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy.

The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part.

Read more

Part A is a sequential dose escalation to determine the maximum tolerated dose of andecaliximab in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive andecaliximab only.

Part B is a dose expansion to obtain additional safety and tolerability data for andecaliximab in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, esophagogastric adenocarcinoma, colorectal cancer, or breast cancer. In Part B, participants will receive andecaliximab in combination with standard-of-care chemotherapy.

Being tested
Andecaliximab, Gemcitabine, Nab-paclitaxel, Carboplatin, Pemetrexed
Keywords
Solid Tumor
Medical subject headings
Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AndecaliximabDrug

    Also called GS-5745

    Administered intravenous infusion

  • GemcitabineDrug

    Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

  • Nab-paclitaxelDrug

    Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

  • CarboplatinDrug

    Administered intravenously on Day 1 of each 21-day treatment cycle

  • PemetrexedDrug

    Administered intravenously on Day 1 of each 21-day treatment cycle

  • LeucovorinDrug

    Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

  • OxaliplatinDrug

    Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

  • 5-FUDrug

    Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

  • BevacizumabDrug

    Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

  • IrinotecanDrug

    Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

  • PaclitaxelDrug

    Administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)

Study groups in NCT01803282
Study groupRoleWhat they receive
Part A: ADX 200 mgExperimentalParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 200 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab
Part A: ADX 600 mgExperimentalParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 600 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab
Part A: ADX 1800 mgExperimentalParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 1800 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug
Receives: Drug: Andecaliximab
Part B: PAC, ADX 800 mgExperimentalParticipants with PAC will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (gemcitabine and nab paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Gemcitabine; Drug: Nab-paclitaxel
Part B: LAC, ADX 1200 mgExperimentalParticipants with lung adenocarcinoma (LAC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and pemetrexed, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Carboplatin; Drug: Pemetrexed
Part B: LSC, ADX 1200 mgExperimentalParticipants with lung squamous cell carcinoma (LSC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and paclitaxel, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Carboplatin; Drug: Paclitaxel
Part B: EGC, ADX 800 mgExperimentalParticipants with esophagogastric adenocarcinoma (EGC) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+oxaliplatin+5-fluorouracil {5-FU} [mFOLFOX6], on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU
Part B: FL CRC, ADX 800 mg+BEV 5 mg/kgExperimentalParticipants with colorectal cancer (CRC) will receive first-line (FL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab
Part B: FL CRC, ADX 800 mg+BEV 10 mg/kgExperimentalParticipants with CRC will receive FL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab
Part B: SL CRC, ADX 800 mg+BEV 5 mg/kgExperimentalParticipants with CRC will receive second-line (SL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+irinotecan+5-FU [FOLFIRI] and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan
Part B: SL CRC, ADX 800 mg+BEV 10 mg/kgExperimentalParticipants with CRC will receive SL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (FOLFIRI and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan
Part B: BRCA, ADX 800 mgExperimentalParticipants with breast cancer (BRCA) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Receives: Drug: Andecaliximab; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    Measured: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

  2. Percentage of Participants Experiencing Laboratory Abnormalities

    Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

    Measured: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2013 (estimated)
  2. Study start29 Mar 2013
  3. Primary completion23 Apr 2019
  4. Study completion23 Apr 2019

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
236 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01803282
Sponsor's protocol ID
GS-US-296-0101
Status last verified
May 2020
First submitted
27 Feb 2013
Last updated
2 Jun 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Shah MA, Starodub A, Sharma S, Berlin J, Patel M, Wainberg ZA, Chaves J, Gordon M, Windsor K, Brachmann CB, Huang X, Vosganian G, Maltzman JD, Smith V, Silverman JA, Lenz HJ, Bendell JC. Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study. Clin Cancer Res. 2018 Aug 15;24(16):3829-3837. doi: 10.1158/1078-0432.CCR-17-2469. Epub 2018 Apr 24.

    PubMed 29691300

  • Lenz H, Park H, Shah MA, Berlin JD, Bruetman D, Chaves J, et al. Results of a phase I study of andecaliximab in combination with mFOLFOX6 and bevacizumab in patients with previously untreated metastatic colorectal cancer. Annals of Oncology (2018) 29 (suppl_8): viii150-viii204

  • Wainberg Z, Bendell J, Lenz H, Baron A, Berlin J, Bessudo A, et al. Results from a phase I study of andecaliximab in combination with FOLFIRI and bevacizumab in patients with second line metastatic colorectal cancer. Journal of Clinical Oncology 36, no. 15_suppl (May 20, 2018) 3578-3578

  • Bendell J, Patel M, Brachmann C, Huang X, Maltzman J, Smith V, et al. Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer [Abstract 363] 2017 American Society of Clinical Oncology Gastrointestinal Cancers Symposium

  • Brachmann C, Zhang Y, Zavodovskaya M, Hu J, Maltzman J, Smith V, et al. Evaluating collagen neoepitopes as pharmacodynamic biomarkers of GS-5745, an MMP9 inhibitor, in advanced gastric cancer [Abstract 58] 2017 American Society of Clinical Oncology Gastrointestinal Cancers Symposium

  • Juric V, Mikels-Vigdal A, O'Sullivan C, Greenstein A, Stefanutti E, Barry-Hamilton V, et al. Inhibition of MMP9 improves anti-tumor immunity by changing the tumor microenvironment to promote T cell trafficking and activation. [Abstract 653/27]. 2017 American Association for Cancer Research Annual Meeting 110th Annual Meeting; 2017 01 April-05 April; Washington, DC

  • Zavodovskaya M, Zhang Y, Xiao Y, Maltzman J, Smith V, Brachmann C, et al. Exploratory Serum Biomarker Analysis in Gastric Cancer Patients Treated with GS-5745, an MMP9 Inhibitor, in Combination with mFOLFOX6 [Abstract 4463/24]. 2017 American Association for Cancer Research Annual Meeting 110th Annual Meeting; 2017 01 April-05 April; Washington, DC

  • Bendell J, Huang X, Smith V, Maltzman J, Starodub A. Results of a phase I study of GS-5745 in combination with gemcitabine and nab-paclitaxel in patients (pts) with advanced pancreatic cancer [abstract e15683] 2016. J Clin Oncol 34 supplemental

  • Shah M, Starodub A, Wainberg Z, Smith V, Maltzman J, Bendell J. Results of a phase I study of GS-5745 in combination with mFOLFOX in patients with advanced unresectable gastric / GE junction tumors [Poster 4033]. American Society of Clinical Oncology (ASCO) 52nd Annual Meeting; 2016 03 June- 07 June; Chicago, IL

  • Bendell J, Starodub A, Sharma S, Wainberg Z, Shah M, Thai D. Phase I Study of GS-5745 Alone and in Combination with Chemotherapy in Patients with Advanced Solid Tumors [Poster 4030]. American Society of Clinical Oncology (ASCO) 51st Annual Meeting; 2015 29 May-02 June; Chicago, IL

  • Marshall DC, Lyman SK, McCauley S, Kovalenko M, Spangler R, Liu C, Lee M, O'Sullivan C, Barry-Hamilton V, Ghermazien H, Mikels-Vigdal A, Garcia CA, Jorgensen B, Velayo AC, Wang R, Adamkewicz JI, Smith V. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS One. 2015 May 11;10(5):e0127063. doi: 10.1371/journal.pone.0127063. eCollection 2015.

    PubMed 25961845

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Andecaliximab, Gemcitabine and Nab-paclitaxel in people with Pancreatic Cancer and Non-small Cell Lung Cancer, run by Gilead Sciences at 18 sites in United States.

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 25 inclusion and 5 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 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 4 May 2020). 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?

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (time frame: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01803282, which also lists 11 linked publications.

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 2 Jun 2020.

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