Breast NeoplasmPhase 1TenatumomabNCT02602067

131Iodine-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients

A Phase 1 study testing 131I-Tenatumomab in people with Breast Neoplasm and Head and Neck Neoplasm, run by sigma-tau i.f.r. S.p.A. at 7 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Breast Neoplasm, Head and Neck Neoplasm, Skin Neoplasm
What is being tested?: 131I-Tenatumomab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 7 sitesin 2 countries
Study dates: Nov 2015to 30 Apr 2017
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1. Written informed consent.
2. A patient who has (a) a histologically documented advanced tumor that has relapsed from, or is refractory to, standard treatment and for which no other standard treatment is available and (b) confirmed Tenascin-C expression obtained through a biopsy on at least one reachable tumor lesion.
These patients will have failed one or more prior therapeutic line and had assessable and measurable disease expression, but were not considered eligible for other standard approaches with curative intent, as assessed by the Investigator.
3. Agreement to hemopoietic stem cell collection procedures (the procedure will be performed upon clinical evaluation of the Investigator and if deemed necessary in the interest of the patient).
4. Male or female ≥18 years of age
5. Eastern Cooperative Oncology Group (ECOG), or WHO performance status of ≤ 2 or Karnofsky > 60

Show all 25Show fewer

6. Life expectancy of at least 3 months.
7. Negative pregnancy test for all women of child-bearing potential. Appropriate contraception (one highly effective method or a combination of acceptable methods) is to be used during the study period and until 90 days after the last follow-up visit (End of Study Visit)
8. Hematological, thyroid, liver, cardiac and renal function test results ≤ grade 2 toxicity (according to US National Cancer Institute's "Common Terminology Criteria for Adverse Events v4.03 [CTCAE]"), e.g.:
Haematology:
Hematocrit ≥ 30%
Hemoglobin ≥ 9.0 g/dl
White blood cell count ≥ 3 x 109/L
Neutrophils > 1.5 x109/L
Platelets ≥ 100x 109/L
Thyroid:
Free-Triiodothyronine and Free-Thyroxine ≤ 3 times upper limit of normal or >3 times lower limit of normal.
Liver:
Alanine transaminase, Aspartate transaminase, Alkaline Phosphatase ≤ 2.5 times institutional upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases.
Bilirubin ≤ 1.5 x ULN or ≤3 x ULN in presence of liver metastases.
Renal:
Urine protein: ≤30 mg/dl or dipstick: ≤3
eGFR≥60 ml/min/1.73 m2 (with Chronic kideny disease-Epidemiology collaboration formula)
Cardiac
Resting Ejection Fraction (EF) ≥ 50%

Who cannot join

1. Known hypersensitivity to Tenatumomab, Iodine or any excipient.
2. Active infection at screening or history of severe infection within the previous 2 months, if considered clinically relevant by the Investigator.
3. Positive test to Human Immunodeficiency Virus (HIV) and/or chronically active Hepatitis B or C.
4. Patients with primary Central nervous system tumor or cerebral metastases.
5. Administration of another investigational medicinal product within 45days before the screening period.
6. Previous treatment with any radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used prior to the administration of study drug.

Show all 13Show fewer

7. History of somatic or psychiatric disease/condition that may interfere with the objectives of the study.
8. Major illness, trauma, or surgery within 2 weeks before the screening period, if considered clinically significant by the Investigator.
9. Patient who underwent chemotherapy and/or radiation therapy and/or treatments with biologics (which are not to be of murine origin) within 4 weeks before the screening period.
10. Women who are breast feeding, due to the potential risk of damage to the infant.
11. Men unwilling to use appropriate contraceptive methods during the study and up to 90 days after the last follow-up visit (End of Study Visit).
12. Bladder catheterization cannot be performed, or the patient is unwilling to be catheterized if necessary.
13. Murine antibodies treated patients. It is at the discretion of the Investigator to exclude patients who have worsened considerably from screening to Day -1.

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

Italy4 sites

Istituto Nazionale Dei Tumori Irccs - Fondazione "G. Pascale"
Naples, 80131
University of Study of Pisa
Pisa, 65126
S. Maria Nuova Hospital - Irccs
Reggio Emilia, 42123
Humanitas Clinical Institute
Rozzano MI, 20089

Other trials in Italy

France3 sites

Institut Bergonnie
Bordeaux, 33076
Centre Leon Berard
Lyon, 69373
Icm Val D'Aurelle
Montpellier, 34298

Other trials in France

About this study

Official title: A Dose Escalation Study to Evaluate Safety, Tolerability Dosimetry, Pharmacokinetics and Preliminary Efficacy of 131I-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients

Tenatumomab is a Sigma-Tau developed new anti-Tenascin antibody. It is a murine monoclonal antibody directed towards Tenascin-C. By means of this antibody, Tenascin-C expression was studied on a commercial tissue array slides each carrying malignant breast, colorectal, lung, ovarian or B and T cell Non-Hodgkin Limphoma tissue sections. All these cancers type showed positivity to Tenascin-C between the 64% and 13.3%. Consequently, Sigma-tau is exploring the use of the 131I-labeled Tenatumomab for anti-cancer radioimmunotherapy.

Read the detailed description

This will be an open-label dose escalation study. The study will be conducted in two steps:

STEP A aims to identify the optimal amount of antibody to convey the specific radio-label activity of radionuclide.
STEP B will be conducted with the amount of antibody chosen in STEP A, and an escalating radio-labeled therapeutic dose response curve will be performed (3.5 to 5.5 GBq) A maximum of 36 evaluable patients suffering from treatment-refractory Tenascin-C positive tumors.

This dose escalation study will be evaluated using descriptive statistics: no sample size calculation was performed

Primary objectives

To identify the Maximum Tolerated Dose (MTD) and assess Safety and Tolerability of i.v. infused 131I-Tenatumomab.
To identify the optimal amount of unlabeled Tenatumomab able to convey 131I- Tenatumomab with the highest Tumor/nonTumor ratio.
To evaluate the whole body Dosimetry (safety dosimetry) and Tumor to normal tissue ratio (T/nT ratio, referred to AUC) of i.v.infused 131I-Tenatumomab.
To evaluate intra-lesional distribution and retention of 131I-Tenatumomab and to record individual lesion dosimetry.
To evaluate systemic biodistribution, pharmacokinetics, urinary excretion and dose linearity of 131I-Tenatumomab.

Secondary objectives

To evaluate proportional 131I-Tenatumomab tumor binding, as a function of the total load.
To evaluate Pharmacokinetics of Tenatumomab (protein and protein related materials) in serum.
To evaluate preliminary Efficacy of 131I-Tenatumomab based on disease response rate (Complete Response, Partial Response, Stable Disease) and patient's general clinical condition by ECOG performance status assessment.

Conditions: Breast Neoplasm, Head and Neck Neoplasm, Skin Neoplasm, Respiratory Tract Neoplasm, Urogenital Neoplasm, Digestive System Neoplasm
Being tested: 131I-Tenatumomab
Medical subject headings: Breast Neoplasms, Head and Neck Neoplasms, Skin Neoplasms, Respiratory Tract Neoplasms, Urogenital Neoplasms, Digestive System Neoplasms, Pancreatic Neoplasms, Neoplasms, Connective and Soft Tissue

What participants receive

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

131I-TenatumomabCombination product
Also called Tenatumomab/ST2146
I131anti-Tenascin monoclonal antibody administered to be targeted on neoplasms expressing Tenascin-C

Study groups in NCT02602067
Study group	Role	What they receive
131I-Tenatumomab	Experimental	Diagnostic: each patient will receive one single i.v. infusion of 370 MBq±10% 131I-Tenatumomab in 10 ml of saline (conveyed by 10 ±10%, 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333 ° µl / min). Therapeutic: each patient will receive one single i.v. infusion, escalating 131I-Tenatumomab dose starting at 2.5 GBq±10%,with escalation steps of 1 GBq, up to 5.5 GBq±10% in 10 ml of saline, (conveyed by 10 ±10% , 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333° µl / min) Receives: Combination Product: 131I-Tenatumomab

What is being measured

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

Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03)
no more details necessary
Measured: up to six weeks

Secondary outcomes (1)

Adverse Events
no more details necessary
Measured: up to 1 year

Timeline

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

Nov 201530 Apr 2017

First posted11 Nov 2015 (estimated)
Study startNov 2015
Primary completion30 Apr 2017
Study completion30 Apr 2017

Why it stopped: Uptake of drug into the tumour lesion was negligible

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Breast NeoplasmStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Not applicable
Intervention model: Single group
Model description: Tenatumomab infusion
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02602067
Sponsor's protocol ID: TENATUMOMAB/ST2146-CR-14-001
Other IDs: 2014-003832-38, 2014
Acronym: Tenatumomab
Status last verified: Jan 2018
First submitted: 9 Nov 2015
Last updated: 18 Sep 2018
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Neoplasm trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Dose Escalation Study to Evaluate Safety, Tolerability Dosimetry, Pharmacokinetics and Preliminary Efficacy of 131I-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients
ClinicalTrials.gov ID: NCT02602067
Acronym / sponsor ID: Tenatumomab / TENATUMOMAB/ST2146-CR-14-001
Conditions: Breast Neoplasm, Head and Neck Neoplasm, Skin Neoplasm, Respiratory Tract Neoplasm, Urogenital Neoplasm, Digestive System Neoplasm
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Uptake of drug into the tumour lesion was negligible
Enrolment: 2 participants (actual)
Lead sponsor: sigma-tau i.f.r. S.p.A.Industry (pharma, biotech, devices)
Collaborators: Medpace, Inc.
Study start: Nov 2015
Primary completion: 30 Apr 2017 (actual)
Study completion: 30 Apr 2017 (actual)
First posted: 11 Nov 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This will be an open-label dose escalation study. The study will be conducted in two steps:

STEP A aims to identify the optimal amount of antibody to convey the specific radio-label activity of radionuclide.
STEP B will be conducted with the amount of antibody chosen in STEP A, and an escalating radio-labeled therapeutic dose response curve will be performed (3.5 to 5.5 GBq) A maximum of 36 evaluable patients suffering from treatment-refractory Tenascin-C positive tumors.

This dose escalation study will be evaluated using descriptive statistics: no sample size calculation was performed

Primary objectives

To identify the Maximum Tolerated Dose (MTD) and assess Safety and Tolerability of i.v. infused 131I-Tenatumomab.
To identify the optimal amount of unlabeled Tenatumomab able to convey 131I- Tenatumomab with the highest Tumor/nonTumor ratio.
To evaluate the whole body Dosimetry (safety dosimetry) and Tumor to normal tissue ratio (T/nT ratio, referred to AUC) of i.v.infused 131I-Tenatumomab.
To evaluate intra-lesional distribution and retention of 131I-Tenatumomab and to record individual lesion dosimetry.
To evaluate systemic biodistribution, pharmacokinetics, urinary excretion and dose linearity of 131I-Tenatumomab.

Secondary objectives

To evaluate proportional 131I-Tenatumomab tumor binding, as a function of the total load.
To evaluate Pharmacokinetics of Tenatumomab (protein and protein related materials) in serum.
To evaluate preliminary Efficacy of 131I-Tenatumomab based on disease response rate (Complete Response, Partial Response, Stable Disease) and patient's general clinical condition by ECOG performance status assessment.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Tenatumomab infusion

Arm	Type	Receives
131I-Tenatumomab	Experimental	Combination Product: 131I-TenatumomabDiagnostic: each patient will receive one single i.v. infusion of 370 MBq±10% 131I-Tenatumomab in 10 ml of saline (conveyed by 10 ±10%, 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333 ° µl / min). Therapeutic: each patient will receive one single i.v. infusion, escalating 131I-Tenatumomab dose starting at 2.5 GBq±10%,with escalation steps of 1 GBq, up to 5.5 GBq±10% in 10 ml of saline, (conveyed by 10 ±10% , 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333° µl / min)

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (25 listed)

1. Written informed consent.
2. A patient who has (a) a histologically documented advanced tumor that has relapsed from, or is refractory to, standard treatment and for which no other standard treatment is available and (b) confirmed Tenascin-C expression obtained through a biopsy on at least one reachable tumor lesion.
These patients will have failed one or more prior therapeutic line and had assessable and measurable disease expression, but were not considered eligible for other standard approaches with curative intent, as assessed by the Investigator.
3. Agreement to hemopoietic stem cell collection procedures (the procedure will be performed upon clinical evaluation of the Investigator and if deemed necessary in the interest of the patient).
4. Male or female ≥18 years of age

Key exclusion criteria (13 listed)

1. Known hypersensitivity to Tenatumomab, Iodine or any excipient.
2. Active infection at screening or history of severe infection within the previous 2 months, if considered clinically relevant by the Investigator.
3. Positive test to Human Immunodeficiency Virus (HIV) and/or chronically active Hepatitis B or C.
4. Patients with primary Central nervous system tumor or cerebral metastases.
5. Administration of another investigational medicinal product within 45days before the screening period.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
131I-TenatumomabAlso: Tenatumomab/ST2146I131anti-Tenascin monoclonal antibody administered to be targeted on neoplasms expressing Tenascin-C	Combination product	131I-Tenatumomab

Primary outcome

Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03)
Time frame: up to six weeks
no more details necessary

1 secondary outcome

Adverse Events
Time frame: up to 1 year

Results and safety

The study was stopped early (reason given: Uptake of drug into the tumour lesion was negligible). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.

Related trials for Breast Neoplasm

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

SECONDO LASTORIA, M.D. study chair

ISTITUTO NAZIONALE DEI TUMORI IRCCS - FONDAZIONE "G. PASCALE" NAPLES - ITALY

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 131I-Tenatumomab in people with Breast Neoplasm and Head and Neck Neoplasm, run by sigma-tau i.f.r. S.p.A. at 7 sites in 2 countries.

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 13 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: stopped early, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Italy, France. 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?

The study was stopped early (reason given: Uptake of drug into the tumour lesion was negligible). Results are not available in the source record.

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?

Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03) (time frame: up to six weeks). 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 NCT02602067.

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 18 Sep 2018.