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Advanced Solid TumorPhase 1NCT02870036

Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics of Simmitecan Monotherapy and Combination in Patients With Advanced Solid Tumors

A Phase 1 study testing Simmitecan, 5-fluorouracil and Leucovorin Calcium and Thalidomide in people with Advanced Solid Tumor and Advanced/Metastatic Colorectal Cancer, run by Haihe Biopharma Co., Ltd. at 9 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study evaluates the safety, tolerability, preliminary efficacy and pharmacokinetics of Simmitecan in patients with advanced solid tumors and Simmitecan, 5-fluorouracil and Leucovorin Calcium,thalidomide in patients with advanced solid tumor or advanced/metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Simmitecan, 5-fluorouracil and Leucovorin Calcium and Thalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
243 participants
Where
9 sitesChina
Study dates
Oct 2016to Dec 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who have fully understood the study, and are willing to sign the informed consent (ICF);
  • Patients with advanced solid tumor confirmed by histopathology and/or cytology were enrolled in Parts 1 and 2 of the study; Four groups of patients with advanced solid tumor confirmed by histopathology and/or cytology were enrolled in Part 3 of the study: Group 1 consisted of patients with rectal carcinoma, Group 2 consisted of patients with gastric carcinoma and esophageal carcinoma, Group 3 consisted of patients with biliary duct carcinoma and pancreatic carcinoma, and Group 4 consisted of patients with gastro-entero-pancreatic neuroendocrine carcinoma. Patients with advanced or metastatic CRC confirmed by histopathology and/or cytology were enrolled in Part 4 of the study; In Part 5 of the study, patients with advanced gastrointestinal tumor (including biliary tumor [gallbladder carcinoma, intra- or extra-hepatic biliary carcinoma], pancreatic carcinoma, hepatocellular carcinoma, esophageal carcinoma, gastric carcinoma, colorectal carcinoma, gastrointestinal stromal carcinoma, and gastro-entero-pancreatic neuroendocrine carcinoma) confirmed by histopathology were enrolled; In Part 6 of the study, patients with advanced gastrointestinal tumor (tentatively determined as biliary tumor, hepatocellular carcinoma, pancreatic carcinoma, and colorectal carcinoma); At least 5 unstained slices of tumor tissues must be obtained at baseline from patients participating in Parts 5 and 6 of the study: Primary lesion samples at the initial diagnosis or archived recently were acceptable. They were used to detect protein expression level of SOD1 and other related molecules to and tumor immunity related indicators.
  • Note: patients being enrolled in part 2 of the study should be those with advanced solid tumor who are suitable for therapeutic regimen of Simmitecan combined with 5 FU/LV as judged by the investigator;
  • Patients who had failed standard treatments for advanced cancer, or are intolerant to the current standard treatments, or no suitable standard treatments available for advanced cancer;
  • Patients who have at least one measurable lesion (according to RECIST, version 1.1); note: the lesions previously treated with radiotherapy cannot be regarded as the target lesion, unless the lesion showed clear progression after radiotherapy;
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
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  • Age≥ 18 years and ≤ 70 years, male or female is allowed;
  • Patients with life expectancy of 12 weeks or more;
  • Patients with appropriate organ function as documented by:
  • absolute neutrophil count ≥ 1.5 × 109/L;
  • hemoglobin ≥ 9 g/dL (without RBC transfusion within 14 days);
  • platelet count ≥ 100 × 109/L.
  • serum total bilirubin ≤1.5 times of upper limit of normal (ULN) (for the patients with Gilbert syndrome, total bilirubin is allowed to be ≤ 3 × ULN and direct bilirubin is allowed to be 1.5 × ULN);
  • aspertate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN, or AST and ALT ≤ 5 × ULN for patients with liver metastasis;
  • creatinine clearance ≥ 50 mL/min (calculated by MDRD equation, see appendix 7);
  • international normalized ratio (INR) ≤1.5 × ULN, or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (INR only for patients who were not given anticoagulant therapy).
  • Patients with negative hepatitis b surface antigen; for patients with positive hepatitis b surface antigen, quantitative result of hepatitis b virus (HBV) DNA should be lower than 1000 cps/mL;
  • Toxicity events caused by previous treatments, surgery or radiotherapy have recovered to CTCAE grade 0 or 1 (except for alopecia);
  • Female patients are eligible for the study if the following conditions are met:
  • Patients have no fertility (i.e., physiological infertility), including postmenopausal period (complete menolipsis for more than 1 year) or documented irreversible sterilization operation including hysterectomy, bilateral ovariectomy, or bilateral salpingectomy (instead of tubal ligation);
  • For patients of childbearing potential, the results of serum pregnancy test screening should be negative (within 7 days before the first dose of investigational drug), and breastfeeding is not allowed before the start of the study and throughout the study. Moreover, the patients should agree to take effective contraception measures during the study and within 90 days after the last dose, and should always conduct strict birth control in accordance with the label of drug/appliance and the investigator's instructions. Effective contraception measure is defined as:
  • The sexual partner with removed deferens is the only sexual partner of female patient;
  • Use of any intrauterine device with documented failure rate less than 1% per year;
  • Double contraception, such as spermicide plus male condom, female condom, diaphragm, cervical cap or intrauterine contraceptive device.
  • Male patients should have undergone vasectomy, or agree to take effective contraception measures during the study and within 90 days after the last dose;
  • Patients are able to follow the study procedures, restrictions and requirements at the investigator's discretion.

Who cannot join

  • Patients are still within 5 half-life of previous anticancer chemotherapy, biological agents or other investigational drugs (if 5 half-life exceeds 28 days, calculated as 28 days) at the time of screening;
  • Patients received systemic radiotherapy (including whole brain radiotherapy) within 28 days before enrollment, or received small area radiotherapy (stereotactic radiotherapy of central nervous system (CNS)) within 7 days before enrollment, or have not yet recovered from the previous radiotherapy;
  • Patients have not yet recovered from the toxic effects (except alopecia) caused by previous anti-tumor treatments (> CTCAE grade 1);
  • Patients underwent major surgery or have not yet been fully recovered from pervious surgery (major surgery is defined as grade 3 or 4 surgery specified in "Management Measures for Clinical Application of Medical Technology" implemented on May 1st, 2009).
  • Patients had CNS metastasis or cancer-related epilepsy requiring clinical intervention; however, patients with CNS metastasis who received treatments, or the asymptomatic patient can be enrolled;
  • Patients with a history of allergy to 5-FU or LV;
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  • Patients with active HBV or HCV infection;
  • Patients diagnosed as human immunodeficiency virus (HIV) infection, or are not willing to have HIV test;
  • Patients with clinically significant active infection;
  • Patients with previous or concurrent other malignant tumors (except effectively controlled non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other effectively controlled tumors in the past 5 years even without treatments);
  • Patients with impaired cardiac function or clinically significant heart diseases, including grade 2 or higher congestive heart failure per New York Heart Association (NYHA) classification, arrhythmia, conduction abnormalities requiring treatment, cardiomyopathy, or uncontrolled hypertension;
  • Patients with serious kidney damage requiring kidney dialysis;
  • Patients with serious liver damage, grade B or C end-stage liver diseases per Child-Pugh classification (see appendix 8);
  • Any other diseases or conditions with clinical significance that may affect the protocol compliance or patient's signature of ICF at the investigator's discretion (such as uncontrolled diabetes, etc.);
  • Patients with disease of digestive tract such as duodenal ulcer, ulcerative colitis, intestinal obstruction or other conditions that may cause alimentary tract hemorrhage or perforation as judged by the investigator, or have past medical history of gastric-intestinal perforation or intestinal fistula;;
  • Patient's physical condition cause the risk of investigational drug use, or render the toxicity or AE difficult to explain at the investigator's discretion.
  • Patients who received Irinotecan therapy within 3 months prior to enrollment.
  • Patients with arteriovenous thromboembolic events within the past 6 months, including myocardial infarction, cerebral stroke, deep vein thrombosis, or pulmonary embolism, etc.
  • Patients who were sensitive to Thalidomide (in Parts 5 and 6).
  • Peripheral neuropathy CTCAE ≥ Grade 2 (in Parts 5 and 6).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

China9 sites, 9 recruiting

  • Beijing Cancer Hospital

    Beijin, Beijing Municipality, 100000

    Lin Shen, M.D., 8610-88196561, lin100@medmail.com.cn

    Lin Shen, M.D.

    Recruiting

  • Hunan Cancer Hospital

    Changsha, Hunan, 410013

    Nong Yang, M.D., 13055193557, yangnong0217@163.com

    Nong Yang, M.D.

    Not yet recruiting

  • The Second Affiliated hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 50011

    Yuan Ying, M.D., 13858193601, yuanying1999@zju.edu.cn

    Yuan Ying, M.D.

    Not yet recruiting

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang

    Bai Yu Xian, 13945095085, bai_yuxian@126.com

    Not yet recruiting

  • Jiangsu Cancer Hospital

    Nanjing, Jiangsu

    Feng Ji Feng, M.D, 13901581264

    Not yet recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200000

    Junning Cao, M.D., 13651680209, cao_junning@126.com

    Junning Cao, M.D.

    Not yet recruiting

  • The first hospital of China Medical University

    Shenyang, Liaoning, 110001

    Yunpeng Liu, M.D., 13898865122, cmu_trial@163.com

    Yunpeng Liu, M.D.

    Not yet recruiting

  • Tianjin Cancer Hospital

    Tianjin, Tianjin Municipality, 300060

    Yi Ba, M.D., 13752157916, bayi@tjmuch.com

    Yi Ba, M.D.

    Not yet recruiting

  • Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

    Xianglin Yuan, M.D., 8627-83662299, yxl@medmail.com.cn

    Xianglin Yuan, M.D.

    Not yet recruiting

Other trials in China

About this study

This study evaluates the safety, tolerability, preliminary efficacy and pharmacokinetics of Simmitecan in patients with advanced solid tumors and Simmitecan, 5-fluorouracil and Leucovorin Calcium,thalidomide in patients with advanced solid tumor or advanced/metastatic colorectal cancer.

Being tested
Simmitecan, 5-fluorouracil and Leucovorin Calcium, Thalidomide
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • SimmitecanDrug

  • 5-fluorouracil and Leucovorin CalciumDrug

  • ThalidomideDrug

Study groups in NCT02870036
Study groupRoleWhat they receive
Pharmacokinetic data investigation of SimmitecanExperimentalTo further determine the pharmacokinetic (PK) characteristics of Simmitecan monotherapy in patients with advanced solid tumors
Receives: Drug: Simmitecan
Dose escalation study of Simmitecan combined therapyExperimentalTo determine the maximum tolerated dose (MTD) of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced solid tumor
Receives: Drug: Simmitecan; Drug: 5-fluorouracil and Leucovorin Calcium
Dose extension study of Simmitecan monotherapyExperimentalTo preliminarily evaluate the anti-tumor activity of Simmitecan monotherapy in patients with advanced solid tumors, and to determine the recommended phase II dose (RP2D)
Receives: Drug: Simmitecan
Dose extension study of Simmitecan combined ThalidomideExperimentalTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced/metastatic colorectal cancer (CRC), and to determine RP2D
Receives: Drug: Simmitecan; Drug: Thalidomide
Dose escalation&extension Simmitecan combined ThalidomideExperimentalTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with gastrointestinal tumors, and to determine RP2D and MTD
Receives: Drug: Simmitecan; Drug: Thalidomide
Dose extension study of Simmitecan combined therapyExperimentalTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with specific tumors
Receives: Drug: Simmitecan; Drug: 5-fluorouracil and Leucovorin Calcium

What is being measured

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

  1. Cmax (maximum plasma concentration)

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  2. Tmax (time to maximum plasma concentration)

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  3. AUC (area under the plasma concentration-time curve)

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  4. T½

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  5. CL (systemic clearance)

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  6. Vz (apparent volume of distribution)

    Measured: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan

  7. Adverse events (AE)

    Measured: AEs will be classified by type, incidence, severity (graded per NCI-CTCAE [version 4.03]), time to onset, seriousness and relationship

Secondary outcomes (6)

  1. Objective response rate (ORR)

    Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

    Measured: Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

  2. progression free survival (PFS)

    Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

    Measured: Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

  3. CBR (clinical benefit rate)

    Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

    Measured: Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

  4. DCR (disease control rate)

    Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

    Measured: Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

  5. OS (overall survival)

    Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

    Measured: Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

  6. accumulative excretion rate

    Measured: Accumulative excretion rate within 0-72 h after the first administration of Simmitecan.

Timeline

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

  1. First posted17 Aug 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionDec 2020 (estimated)
  4. Study completionDec 2020 (estimated)

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
Parallel groups
Masking
None (open label)
Enrolment
243 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02870036
Sponsor's protocol ID
GV-LP-102
Status last verified
Jul 2017
First submitted
3 Aug 2016
Last updated
14 Jul 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, Andre T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouche O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. doi: 10.1200/JCO.2013.54.1011. Epub 2014 Oct 6.

    PubMed 25287828

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.

    PubMed 26808342

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Simmitecan, 5-fluorouracil and Leucovorin Calcium and Thalidomide in people with Advanced Solid Tumor and Advanced/Metastatic Colorectal Cancer, run by Haihe Biopharma Co., Ltd. at 9 sites in China.

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 26 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 14 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in China. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax (maximum plasma concentration) (time frame: before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan). The study lists 7 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 NCT02870036, which also lists 2 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 14 Jul 2017.

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