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Effect of DrugsPhase 1/2NCT04044378

Famitinib Plus Camrelizumab & Famitinib Alone & Famitinib Plus Ifosfamide in Advanced Osteosarcoma

A Phase 1/2 study testing Famitinib, Ifosfamide and Camrelizumab in people with Effect of Drugs and Progression, run by Peking University People's Hospital at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Results of previous study showed high objective response but short-term activity of anti-angiogenesis tyrosine kinase inhibitors in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Effect of Drugs, Progression, Pediatric Cancer
What is being tested?
Famitinib, Ifosfamide and Camrelizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteChina
Study dates
15 Aug 2019to 30 Sep 2022
Phase
Phase 1/2
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Provided informed consent and sign the informed consent form;
  • ≥12 years old, male and female (For phase I portion, only 12-17 years old with 12 and 17 years old included; for phase II portion, more than 12 years old);
  • Histopathologically or cytologically confirmed Advanced Osteosarcoma; (Local tumors and solitary pulmonary lesions must be confirmed by pathological diagnosis. Multiple pulmonary metastases need no pathological examination.)
  • Failed to receive chemotherapy for osteosarcoma (including HD-MTX, anthracyclines, DDP and IFO) are defined as those who progress within 6 months after adjuvant chemotherapy and chemotherapy for advanced osteosarcoma, and those who progress over 6 months require the consent of the subject or his legal representative.;
  • Have at least one measurable lesion (in accordance with RECIST v1.1, major diameter ≥10 mm of the measurable lesion in spiral CT scan or short diameter of swollen lymph node ≥15 mm; the lesion with previous local therapy can be used as target lesion after the progression is confirmed in accordance with RECIST v1.1);
  • For subjects with progression after local regional therapy, the local regional therapy (including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic arterial infusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection) must has been completed at least 4 weeks prior to baseline radiological scanning, and any toxicity (except alopecia) induced by local regional therapy must have resolved to ≤ Grade 1 in accordance with national cancer institute - common terminology criteria for adverse event version 4.03 (NCI-CTCAE v4.03);
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  • ECOG-PS score 0-1;
  • With a life expectancy of ≥12 weeks;
  • The body surface area is over 1.2 m2;
  • Have the required screening laboratory values including the following parameters (within 7 days prior to the start of study treatment):
  • Hematology: (except for hemoglobin, no blood transfusion or use of granulocyte colony-stimulating factor [G-CSF] or use of drugs for correction within 14 days prior to screening); Absolute neutrophil count ≥0.75×109/L; Platelet count ≥75×109/L; Hemoglobin ≥80 g/L;
  • Blood biochemistry: (no infusion of albumin within 14 days):
  • Serum albumin ≥25 g/L； Serum total bilirubin ≤1×upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) ≤2.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or Cr clearance >50 mL/min (Cockcroft-Gault formula as below) Man: Cr clearance =((140-age) ×weight)/(72×serum Cr) Woman: Cr clearance =((140-age) ×weight)/ (72×serum Cr) × 0.85 Weight unit: kg; serum Cr unit: mg/mL;
  • Women of childbearing potential: must agree on abstinence (avoid heterosexual intercourse) or use of contraception methods with annual contraceptive failure rate of < 1% following the signature of informed consent form until at least 120 days after the last dose of study drug. The serum human chorionic gonadotropin (HCG) test must be negative within 7 days prior to enrollment in the study; and the subjects must not be in lactating period.
  • If the female subject has menses, has not reached postmenopausal state (absence of menses for ≥ consecutive 12 months, with no other reason found except menopause) and has not received sterilization operation (e.g., hysterectomy, bilateral tubal ligation or bilateral ovariectomy), she would be considered to have childbearing potential.

Who cannot join

  • Other active malignant tumor except advanced osteosarcoma within 5 years or simultaneously. Cured localized tumor, for example, basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of prostate, carcinoma in situs of cervix, breast cancer in situ may be enrolled;
  • History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage, for example, esophageal and fundal varices with hemorrhagic risk, locally active peptic ulcer, persistent fecal occult blood (+) (the fecal occult blood test can be repeated if it is positive at baseline, and gastroduodenoscopy [EGD] would be needed if it is still positive in repeated test; the patient can not be enrolled if the EGD shows esophageal and fundal varices with hemorrhagic risk);
  • Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment;
  • Known genetic or acquired hemorrhage (e.g., coagulation dysfunction) or thrombotic tendency, for example, patient with hemophilia; current or recent (within 10 days prior to the start of study treatment) use of full-dose of oral or intravenous anticoagulant or thrombolytic drug for the purpose of treatment (preventive use of low-dose aspirin or low molecular weight heparin is allowed);
  • Current or recent (within 10 days prior to the start of study treatment) use of aspirin (> 325 mg/day) or dipyridamole, ticlopidine, clopidogrel and cilostazol;
  • Thrombosis or thromboembolic event within 6 months prior to the start of study treatment, for example, cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism;
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  • Cardiac clinical symptom or disease that is not well controlled, for example, (1) > Grade II cardiac insufficiency in accordance with New York Heart Association (NYHA) criteria or color Doppler echocardiography: LVEF (left ventricular ejection fraction) <50%; (2) unstable angina pectoris; (3) myocardial infarction within one year prior to the start of study treatment; (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) QTc > 450 ms (males) or QTc > 470ms (females) (QTc interval is calculated by Fridericia formula; In case QTc is abnormal, it can be detected for three times at an interval of 2 minutes and the average will be taken);
  • Hypertension that can not be well controlled through antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the average of BP readings acquired from ≥2 measurements), allowing to reach the above parameters by the use of antihypertensive therapy; previous hypertensive crisis or hypertensive encephalopathy;
  • Major vascular disease within 6 months prior to the start of study treatment (for example, aortic aneurysm requiring surgical repair or peripheral arterial thrombosis in recent days);
  • Serious, uncured or splitting wound and active ulcer or untreated bone fracture;
  • Major surgical therapy within 4 weeks prior to the start of study treatment (except diagnosis), or expected major surgery during the study;
  • Inability or unwilling to swallow tablets, malabsorption syndrome or any condition affecting gastrointestinal absorption;
  • Intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to the start of study treatment, including incomplete obstruction that is related with the original disease or needs routine parenteral hydration, parenteral nutrition or tube feeding; If the subject has signs/symptoms of incomplete obstruction/ obstructive syndrome/intestinal obstruction at the initial diagnosis receives clear (surgical) therapy to resolve symptoms, the subject may be enrolled;
  • Evidence on intraperitoneal pneumatosis that can not be explained by puncture or recent surgery;
  • Previous or current presence of metastasis to central nervous system;
  • Previous or present history of pulmonary fibrosis, organising pneumonia (e.g., obliterative bronchiolitis), interstitial pneumonia, pneumoconiosis, drug related pneumonitis, idiopathic pneumonia, or allowable previous radiation pneumonitis in the radiation area (fibrosis) for subjects with evidence on active pneumonia or serious pulmonary function impairment on thoracic computed tomography (CT) in screening period that may interfere with the detection and treatment of suspected drug related pulmonary toxicity; active tuberculosis;
  • Any active autoimmune disease or history of autoimmune disease and expected recurrence (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects that can be controlled with hormone replacement therapy only can be enrolled]); subjects with skin diseases that does no need systemic treatment, for example, leukoderma, psoriasis, alopecia, those with controlled type I diabetes by insulin or those with asthma that has been completely resolved in childhood and with no need of any intervention can be enrolled; while subjects with asthma who need bronchodilator for medical intervention can not be enrolled;
  • Current use of immunosuppressive medication, or systemic corticosteroid therapy to achieve the objective of immunosuppression (Prednisone at the dose of >10mg/day or equivalent), and continuous use within two weeks prior signing informed consent form;
  • Use of strong CYP3A4/CYP2C19 inducers, including rifampicin (and its analogues) and St. Jonhn's Wort, or strong CYP3A4/CYP2C19 inhibitors within two weeks prior to the signature of informed consent form;
  • Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug;
  • Severe infection within 4 weeks prior to the start of study treatment, including but not limited to hospitalization for infection, bacteremia or complications of severe pneumonia; oral or intravenous therapeutic antibiotics within two weeks prior to the start of study treatment (for example, subjects who are given with preventive antibiotics for prevention of urinary tract infection or exacerbation of chronic obstructive pulmonary disease are eligible for participation in the study);
  • Congenital or acquired immunodeficiency (e.g., HIV infection);
  • Combined hepatitis B and hepatitis C co-infection;
  • Previous treatment with other PD-1 antibody or other immunotherapy against PD-1/PD-L1, or previous use of other small molecules of anti-angiogenesis TKI drugs, such as pazopanib, sorafenib;
  • Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it must be completed at least 2 weeks prior to the start of study treatment, and the adverse event induced by radiotherapy must have resolved/improved to ≤CTCAE Grade 1;
  • Treatment of other investigational product(s) within 28 days prior to the start of study treatment;
  • Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators, such as alcoholism, drug abuse, other serious diseases (including mental disorders) requiring concomitant therapy, with serious laboratory examination abnormality, with family or social factors, that may affect subject's safety.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Lu Xie

    Beijing, Beijing Municipality, 100044

Other trials in China

About this study

Official title: Famitinib Malate (SHR1020) Plus Camrelizumab (SHR 1210) Versus Famitinib Malate Alone Versus Famitinib Malate Plus Ifosfamide Locally Advanced, Unresectable or Metastatic Osteosarcoma Progression Upon Chemotherapy: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial

Results of previous study showed high objective response but short-term activity of anti-angiogenesis tyrosine kinase inhibitors in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. The investigators had completed an prospective phase 2 trial of the combination of apatinib and camrelizumab on advanced osteosarcoma and showed prolonged progression-free survival for this combination. Famitinib is a novel tyrosine kinase inhibitor targeting VEGFR-2, -3 and FGFR-1, -2, -3, -4 with high affinity, which showed broad antitumor activity against a variety of xenograft models.

A Study to Compare the Efficacy and Safety of Levatinib with or without Ifosfamide and Etoposide in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma showed promising median PFS of 11.3 months. Thus we also try to investigate the combination efficacy of TKIs with chemotherapy in advanced osteosarcoma.

This study aims to investigate the recommended phase 2 dose for pediatric use of famitinib in combination with camrelizumab and trys to explore the efficacy and safety for single drug famitinib, famitinib and camrelizumab and famitinib and ifosfamide in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.

Being tested
Famitinib, Ifosfamide, Camrelizumab
Keywords
famitinib, camrelizumab, advanced osteosarcoma, recommended phase 2 dose, efficacy, ifosfamide
Medical subject headings
Disease Progression, Neoplasms

What participants receive

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

  • FamitinibDrug

    famitinib with RP2D orally daily

  • IfosfamideDrug

    ifosfamide 1.8g/m2/d d1-3, 15-17 Q4W infusion

  • CamrelizumabDrug

    Also called camralizumab

    camrelizumab 200mg infusion once Q2W

Study groups in NCT04044378
Study groupRoleWhat they receive
Arm A: famitinib and camrelizumabExperimentalIn the dose-defining phase I portion, camrelizumab was given at a fixed dose of 200mg Q2W, while the de-escalated 3+3 design was used to detect the recommended dose of famitinib from an initial level of 15mg orally taken daily. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the phase II portion, famitinib will be orally taken daily with RP2D together with camrelizumab intravenous infusion at a dose of 200 mg over 30 minutes, once every two weeks (Q2W), 4 weeks (28 days) as one treatment cycle.
Receives: Drug: Famitinib; Drug: Camrelizumab
Arm B: famitinib aloneActive comparatorOnly phase II portion (Phase I have been completed): famitinib will be 20mg orally taken daily, 4 weeks (28 days) as one treatment cycle.
Receives: Drug: Famitinib
Arm C: Famitinib and IfofamideExperimentalOnly phase II protion (Phase I have been completed): famitinib will be 20mg orally taken daily, 4 weeks (28 days) as one treatment cycle together with ifofamide 1800 mg/m^2/day intravenous infusion will be administered on Days 1 to 3 and 15-17 of each 28-day cycle for a total of 5 cycles.
Receives: Drug: Famitinib; Drug: Ifosfamide

What is being measured

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

  1. Objective response rate

    CR+PR according to RECIST 1.1

    Measured: 3 months

  2. Progression-free Survival, PFS

    Progression-free survival is defined as time from randomisation to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment or randomisation.

    Measured: 6 months

Secondary outcomes (2)

  1. Overall Survival, OS

    Overall survival is was defined as time from randomisation to the first occurrence of death from any cause within 63 days of last response assessment or randomisation. randomisation to the first occurrence of progression of disease orrandomisation.

    Measured: 12 months

  2. Duration of response, DOR

    Duration of response is defined as from the time of occurence of best overall response to progression or death for the proportion of patients achieving an overall response.

    Measured: 6 months

Timeline

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

  1. First posted5 Aug 2019
  2. Study start15 Aug 2019
  3. Primary completion30 Sep 2021 (estimated)
  4. Study completion30 Sep 2022 (estimated)

Why it stopped: toxicity

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04044378
Sponsor's protocol ID
PKUPH-sarcoma 08
Other IDs
CSSG
Status last verified
May 2020
First submitted
1 Aug 2019
Last updated
19 May 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial. Oncologist. 2019 Jul;24(7):e542-e550. doi: 10.1634/theoncologist.2018-0542. Epub 2018 Dec 17.

    PubMed 30559126

  • Xie L, Guo W, Wang Y, Yan T, Ji T, Xu J. Apatinib for advanced sarcoma: results from multiple institutions' off-label use in China. BMC Cancer. 2018 Apr 6;18(1):396. doi: 10.1186/s12885-018-4303-z.

    PubMed 29625604

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Famitinib, Ifosfamide and Camrelizumab in people with Effect of Drugs and Progression, run by Peking University People's Hospital at 1 site 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 15 inclusion and 27 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: withdrawn, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Objective response rate (time frame: 3 months). 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 NCT04044378, 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 19 May 2020.

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