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Recurrent GlioblastomaPhase 1NCT03722342

TTAC-0001 and Pembrolizumab Combination phase1b Trial in Recurrent Glioblastoma

A Phase 1 study testing TTAC-0001 and pembrolizumab combination in people with Recurrent Glioblastoma, run by PharmAbcine at 2 sites in Australia.

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 The sponsor has not verified this record for over two years, so it may be out of date.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 is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with recurrent glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Glioblastoma
What is being tested?
TTAC-0001 and pembrolizumab combination
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesAustralia
Study dates
16 Jan 2019to 30 Sep 2022
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

Who may be able to join

  • Diagnosed with primary glioblastoma by histopathological examination and confirmed recurrent glioblastoma by magnetic resonance imaging (MRI) scans after completing standard of care (Stupp protocol) concomitant temozolomide chemotherapy with radiotherapy (CCRT)
  • At least one confirmed measurable lesion by RANO criteria
  • Karnofsky Performance Status (KPS) ≥80
  • A person who satisfies the following criteria in haematologic, renal, and hepatic function tests performed within 7 days prior to screening:
  • Haematologic tests
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
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  • Platelets ≥ 100 x 109/L
  • Haemoglobin ≥ 9.0 g/dL
  • Blood coagulation tests
  • Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (ULN)
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
  • Hepatic function tests
  • Total bilirubin ≤ 1.5 x UNL
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
  • Renal function test
  • ≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN
  • At least 12 weeks of expected survival time
  • The patient (or legally acceptable representative if applicable) is able and willing to provide written informed consent for the trial

Who cannot join

  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] controlled by curative therapy are not excluded)
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
  • Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
  • Uncontrolled seizures
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  • Class III or IV heart failure by New York Heart Association (NYHA) classification
  • Has oxygen-dependent chronic disease
  • Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
  • History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
  • History of severe arterial thromboembolic event within 12 months of start of study drug
  • Serious grade 4 venous thromboembolic event including pulmonary embolism
  • History of hypertensive crisis or hypertensive encephalopathy
  • History of posterior reversible encephalopathy syndrome
  • Planned surgery within 4 weeks post last dose
  • Moderate to severe proteinuria as demonstrated by urine dipstick for proteinuria ≥2+. For patients with ≥2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible
  • Requiring therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anticoagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed
  • Not recovered below National Cancer Institute-Common Terminology for Adverse Events (NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy (patient with ≤ Grade 2 neuropathy or alopecia may be eligible)
  • Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 2 weeks prior to the baseline visit
  • Undergone major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted thoracoscopic surgery [VATS] or open-and-closed [ONC] surgery)
  • Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
  • Pregnant* or lactating females, and females/males of childbearing potential who do not agree to a reliable and adequate method of contraception
  • A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drugs
  • Unable to participate in the trial according to the investigator's decision
  • Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Known human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
  • Known active hepatitis B or hepatitis C infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
  • Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted
  • Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official title: A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Recurrent Glioblastoma

This is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with recurrent glioblastoma.

Being tested
TTAC-0001 and pembrolizumab combination
Medical subject headings
Glioblastoma

What participants receive

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

  • TTAC-0001 and pembrolizumab combinationDrug

    • Investigational product (IP): TTAC-0001 and Pembrolizumab (Merck, Keytruda®)
    • Treatment groups: 3 dose levels
    • Dose level 1 (optimal starting dose): TTAC-0001 12 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 2 (first escalation dose): TTAC-0001 16 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 0 (de-escalation dose): TTAC-0001 8 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Cycle: 3 weeks (21 days per cycle)
Study groups in NCT03722342
Study groupRoleWhat they receive
TTAC-0001 and pembrolizumabExperimentalTTAC-0001 and pembrolizumab combination therapy will be administered.
Receives: Drug: TTAC-0001 and pembrolizumab combination

What is being measured

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

  1. Dose limiting toxicities

    The frequency and percentage of DLT will be presented by dose level

    Measured: During the first cycle (every cycle is 21 days) of treatment

  2. Adverse events

    The frequency and percentage of AEs will be presented by dose level

    Measured: From the screening visit to the end of treatment visit (time of progressive disease or 2 years)

  3. Immunogenicity

    Presence anti-drug antibody (ADA) will be listed

    Measured: From screening visit to end of treatment visit (time of progressive disease or 2 years)

Secondary outcomes (4)

  1. Overall response rate

    complete response (CR) or partial response (PR) by RANO criteria

    Measured: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days)

  2. Disease control rate

    complete response (CR), partial response (PR) or stable disease (SD) by RANO criteria

    Measured: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days)

  3. Progression free survival

    Period from the date of the drug administration to the disease progression time point

    Measured: From screening visit to end of treatment visit (time of progressive disease or 2 years)

  4. Overall survival

    Period from the date of the drug administration to the patient's death

    Measured: From screening visit to date of patient's death (assessed up to 2 year after end of treatment visit)

Timeline

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

  1. First posted26 Oct 2018
  2. Study start16 Jan 2019
  3. Primary completion4 Nov 2019
  4. Study completion30 Sep 2022 (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
Not applicable
Intervention model
Sequential
Model description
This was mTPI design to start with optimal dose and next dose level is selected accroding to DLT occurrance
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03722342
Sponsor's protocol ID
PMC_TTAC-0001_04
Status last verified
Aug 2022
First submitted
3 Jul 2018
Last updated
17 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TTAC-0001 and pembrolizumab combination in people with Recurrent Glioblastoma, run by PharmAbcine at 2 sites in Australia.

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 18 inclusion and 32 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 17 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. 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?

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 toxicities (time frame: During the first cycle (every cycle is 21 days) of treatment). The study lists 3 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 NCT03722342.

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 17 Aug 2022.

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