Inoperable Solid Tumors or LymphomasPhase 1NCT03188328
Safety, Tolerability, PK, Dosimetry, MTD and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by IV Escalating Doses of [177Lu]DOTA-biotin in Pts With Injectable Solid Tumors or Lymphomas
A Phase 1 study testing AvidinOX and 177Lu-ST2210 in people with Inoperable Solid Tumors or Lymphomas, run by Alfasigma S.p.A. at 1 site in United States.
Trial summary
Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inoperable Solid Tumors or Lymphomas
- What is being tested?
- AvidinOX and 177Lu-ST2210
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2017to 1 Jul 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Presence of inoperable tumor lesion/s from histologically confirmed solid tumors or lymphomas, in patients with at least one lesion ≥ 1 cm and suitable for intra-lesional injection, who have disease progression after treatment with available therapies, or who are intolerant to such treatments
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- If the patient received previous radiation therapy, the total absorbed radiation dose at the bone marrow level must be ≤ 1 Gy
- Life expectancy of at least 3 months
- Total tumor burden requiring ≤ 75 mL AvidinOX injection
- Clotting parameters within normal limits or maximum 25% outside of the the normal ranges
- Haematological and liver function test results ≤ grade 2 toxicity (according to US National Cancer Institute's Common Terminology) Criteria for Adverse Events v4.03 [CTCAE
- Urine protein (dipstick): negative or trace; in case of trace, a urinalysis has to be performed in the local laboratory and have to confirm that such abnormality is not to be considered clinically significant, according to the investigator's judgement
- Creatinine ≤ 1.7 mg/dL
- eGFR> 60% of mean age adjusted normal values
- Written informed consent
Main Exclusion Criteria:
- Known hypersensitivity to Avidin or AvidinOX (e.g. hen egg)
- Known hypersensitivity to ST2210 (DOTA biotin) or any excipient.
- Presence of unreachable (e.g. located in a region that cannot be reached by needle) or untreatable tumor lesions so that the benefit from the treatment of the treatable lesions does not justify patient's inclusion
- Active infection at screening or history of severe infection within the previous 3 months, if clinically relevant at screening as considered by the investigator
- Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C.
- Administration of another investigational medicinal product within 30 days before the screening period.
- Patient who underwent chemotherapy, radiation therapy within 15 days before the screening period
- Previous treatment with any radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used for labeling the respective radiopharmaceutical prior to the administration of study drug.
- Women of child-bearing potential without a serum negative pregnancy test and not willing to refrain from sexual activity or to utilize an adeguate contraceptive methods during all the course of the study
- Men unwilling to use appropriate contraceptive methods during the study and up to six months follow-up period
Trial locations and contacts
1 site in 1 country.
United States1 site
Dep. of Investigational Cancer Therapeutics - U. T. M. D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Solid Tumors or Lymphomas With Injectable Neoplastic Lesions.
Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth but are characterized by poor patient's compliance, significant side effects, high costs and technological complexity hampering wide-spread use. The use of AvidinOX for radionuclide therapy of inoperable cancer lesions will offer a number of advantages compared to current brachytherapy. In fact, the perfusion of a target tissue with AvidinOX, compared to current devices, will allow adapting the therapy to the tumor/organ shape, and it will also make it possible to delay the administration of radioactivity for several days which, according to pre-clinical studies, might be also divided up into repeated doses. AvidinOX linking stably to tissue proteins, does not exhibit the problem of seed migration which is associated with high morbidity. Based on previous findings with AvidinOX in combination with radionuclides in pre-clinical studies as well as data from the clinical use in liver metastases, it can be assumed that intralesional injections of AvidinOX followed by intravenous injections of 177Lu-ST2210 could be a safe and efficacious method for treating inoperable tumor lesions.
Read the detailed description
The primary objectives of this study are:
- To identify the Maximum Tolerated Dose (MTD) of two consecutive repeated IV 177Lu-ST2210 administration following a previous tumor intra-lesion/s injection of AvidinOX.
- To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected 177Lu-ST2210
- To evaluate intra-lesional distribution and retention of {AvidinOX + 177Lu-ST2210}-complex in tumor lesion/s
- To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX + 177Lu-ST2210}- complex
Main secondary objectives are:
- To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection (radiation safety dosimetry)
- To record individual tumor dosimetry
- To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor size and metabolic activity.
- To evaluate damage of tumor cells by radioactivity and immunogenic cell death
- To evaluate whole body safety dosimetry and dose linearity
- To evaluate pharmacokinetics of ST2210 in plasma and urine
- Conditions
- Inoperable Solid Tumors or Lymphomas
- Being tested
- AvidinOX, 177Lu-ST2210
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvidinOXDrug
AvidinOX vial containing 22.5 mg AvidinOX
+ vials containing 10 ml of water for injection (WFI) for the reconstitution in a clear solution with an AvidinOX concentration of 3 mg/ml. One Intralesion administration of a volume of reconstituted AvidinOX equal to about 15 % of the estimated lesion volume
177Lu-ST2210Drug
177Lu-ST2210 dose starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210
177Lu-ST2210Drug
Second dose of 177Lu-ST2210 dose (14 days after the first dose) starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210
| Study group | Role | What they receive |
|---|---|---|
| AvidinOX/177Lu-ST2210 | Experimental | Patients will receive an intralesion injection of AvidinOX followed by two intravenous infusions of 177Lu- ST2210 with a distance of 14 days between them Receives: Drug: AvidinOX; Drug: 177Lu-ST2210 |
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)
Measured: Up to six weeks after the second 177Lu-ST2210 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2017
- Study start7 Aug 2017
- Primary completion30 Jun 2019
- Study completion1 Jul 2019
Why it stopped: low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inoperable Solid Tumors or LymphomasStudies 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
- 3 + 3 dose escalation design
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alfasigma S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vivek Subbiah, MD, Principal investigator, Dep. of Investigational Cancer Therapeutics - U. T. M. D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03188328
- Sponsor's protocol ID
- AvOX/ST2210-CR-15-001
- Status last verified
- Jul 2019
- First submitted
- 13 Jun 2017
- Last updated
- 5 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vesci L, Carollo V, Rosi A, De Santis R. Therapeutic efficacy of intra-tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer. Oncol Lett. 2019 Mar;17(3):3529-3536. doi: 10.3892/ol.2019.10003. Epub 2019 Feb 1.
PubMed 30867794
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Solid Tumors or Lymphomas With Injectable Neoplastic Lesions.
- ClinicalTrials.gov ID
- NCT03188328
- Acronym / sponsor ID
- AvOX/ST2210-CR-15-001
- Conditions
- Inoperable Solid Tumors or Lymphomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment rate
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Alfasigma S.p.A.Industry (pharma, biotech, devices)
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 15 Jun 2017 (actual)
- 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.
Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth but are characterized by poor patient's compliance, significant side effects, high costs and technological complexity hampering wide-spread use. The use of AvidinOX for radionuclide therapy of inoperable cancer lesions will offer a number of advantages compared to current brachytherapy. In fact, the perfusion of a target tissue with AvidinOX, compared to current devices, will allow adapting the therapy to the tumor/organ shape, and it will also make it possible to delay the administration of radioactivity for several days which, according to pre-clinical studies, might be also divided up into repeated doses. AvidinOX linking stably to tissue proteins, does not exhibit the problem of seed migration which is associated with high morbidity. Based on previous findings with AvidinOX in combination with radionuclides in pre-clinical studies as well as data from the clinical use in liver metastases, it can be assumed that intralesional injections of AvidinOX followed by intravenous injections of 177Lu-ST2210 could be a safe and efficacious method for treating inoperable tumor lesions.
Detailed description
The primary objectives of this study are:
- To identify the Maximum Tolerated Dose (MTD) of two consecutive repeated IV 177Lu-ST2210 administration following a previous tumor intra-lesion/s injection of AvidinOX.
- To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected 177Lu-ST2210
- To evaluate intra-lesional distribution and retention of {AvidinOX + 177Lu-ST2210}-complex in tumor lesion/s
- To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX + 177Lu-ST2210}- complex
Main secondary objectives are:
- To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection (radiation safety dosimetry)
- To record individual tumor dosimetry
- To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor size and metabolic activity.
- To evaluate damage of tumor cells by radioactivity and immunogenic cell death
- To evaluate whole body safety dosimetry and dose linearity
- To evaluate pharmacokinetics of ST2210 in plasma and urine
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3 + 3 dose escalation design
| Arm | Type | Receives |
|---|---|---|
| AvidinOX/177Lu-ST2210 | Experimental | Drug: AvidinOX, Drug: 177Lu-ST2210Patients will receive an intralesion injection of AvidinOX followed by two intravenous infusions of 177Lu- ST2210 with a distance of 14 days between them |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| AvidinOXAvidinOX vial containing 22.5 mg AvidinOX + vials containing 10 ml of water for injection (WFI) for the reconstitution in a clear solution with an AvidinOX concentration of 3 mg/ml. One Intralesion administration of a volume of reconstituted AvidinOX equal to about 15 % of the estimated lesion volume | Drug | AvidinOX/177Lu-ST2210 |
| 177Lu-ST2210177Lu-ST2210 dose starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210 | Drug | AvidinOX/177Lu-ST2210 |
| 177Lu-ST2210Second dose of 177Lu-ST2210 dose (14 days after the first dose) starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210 | Drug | AvidinOX/177Lu-ST2210 |
Primary outcome
Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03)
Time frame: Up to six weeks after the second 177Lu-ST2210 infusion
Results and safety
The study was stopped early (reason given: low recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Derived from this study: PubMed 30867794Vesci L, Carollo V, Rosi A, De Santis R. Therapeutic efficacy of intra-tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer. Oncol Lett. 2019 Mar;17(3):3529-3536. doi: 10.3892/ol.2019.10003. Epub 2019 Feb 1.
- Individual participant dataSharing planned: Undecided
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.
Vivek Subbiah, MD principal investigator
Dep. of Investigational Cancer Therapeutics - U. T. M. D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AvidinOX and 177Lu-ST2210 in people with Inoperable Solid Tumors or Lymphomas, run by Alfasigma S.p.A. at 1 site 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?
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 5 Jul 2019. 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 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?
The study was stopped early (reason given: low recruitment rate). 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 after the second 177Lu-ST2210 infusion). 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 NCT03188328, which also lists 1 linked publication.
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 5 Jul 2019.