Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study

NCT04801966 | Terminated DMC

• 1 other identifier: 20/029
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study is looking at outcomes in people with advanced cancers who have exhausted standard treatment options and are accessing off indication or unregistered drugs or combinations of drugs through compassionate access from the manufacturer.

Conditions

Cancer

Outcome Measures

Primary Outcomes (2)

• Safety of the study design as mechanism for administering individualised therapies to individuals with incurable malignancies

  Severity of adverse events as determined by NCI CTCAE v5.0

  At the end of the study, approximately 5 years after the first participant commences treatment

• Feasibility of the study design as mechanism for administering individualised therapies to individuals with incurable malignancies

  Feasibility measured by: Number of treatment plans proposed to the study committee Proportion of treatment plans proposed that are approved Proportion of approved plans for which study drug(s) were obtained Proportion of approved plans for which study drug(s) were obtained and patient was registered on the trial

  At the end of the study, approximately 5 years after the first participant commences treatment

Secondary Outcomes (1)

• Efficacy of individualised therapies in patients registered to the study

  At the end of the study, approximately 5 years after the first participant commences treatment

Study Arms (1)

Treatment

EXPERIMENTAL

All participants will have an individualised treatment plan. The possible treatments that can be prescribed are as follows, they may be given as a single agent or in combination * Trametinib 2 mg/day * Cobimetinib 60 mg/day, on day 1-21 of each 28 day cycle (21 days on, 7 days off) * Binimetinib 45 mg/ twice a day * Alpelisib 300 mg/day * Vemurafenib 960 mg twice a day * Dabrafenib 150 mg twice a day * Encorafenib 450 mg/day * Palbociclib 125 mg/day, on day 1-21 of each 28 day cycle (21 days on, 7 days off) * Ribociclib 600 mg/day, on day 1-21 of each 28 day cycle (21 days on, 7 days off * Abemaciclib 150 mg twice a day * Olaparib 300 mg twice a day * Talazoparib 1 mg/day * Nivolumab 240 mg IV once every two weeks * Atezolizumab 1200 mg IV on day 1 of a 21 day cycle * Pembrolizumab 200 mg IV on day 1 of a 21 day cycle

Drug: Trametinib; Drug: Cobimetinib; Drug: Binimetinib; Drug: Alpelisib; Drug: Vemurafenib; Drug: Dabrafenib; Drug: Encorafenib; Drug: Palbociclib; Drug: Olaparib; Drug: Ribociclib; Drug: Abemaciclib; Drug: Talazoparib; Drug: Nivolumab; Drug: Atezolizumab; Drug: Pembrolizumab

Interventions

Trametinib DRUG

2 mg per day, continuous

Treatment

Cobimetinib DRUG

60 mg/day for 21 days of a 28 day cycle

Treatment

Binimetinib DRUG

45 mg/twice a day, continuous

Treatment

Alpelisib DRUG

300 mg/day, continuous

Treatment

Vemurafenib DRUG

960 mg/twice per day, continuous

Treatment

Dabrafenib DRUG

150 mg/twicce per day, continuous

Treatment

Encorafenib DRUG

450 mg/day, continuous

Treatment

Palbociclib DRUG

125 mg/day, day 1-21 of a 28 day cycle

Treatment

Olaparib DRUG

300 mg/twice per day, continuous

Treatment

Ribociclib DRUG

600 mg/day, on day 1 -21 of a 28 day cycle

Treatment

Abemaciclib DRUG

150 mg twice/day, continuous

Treatment

Talazoparib DRUG

1 mg/day, on day 1 -28 of each 28 day cycle

Treatment

Nivolumab DRUG

240 mg IV once every 2 weeks

Treatment

Atezolizumab DRUG

1200 mg IV on Day 1 of a 21 day cycle

Treatment

Pembrolizumab DRUG

200 mg IV on day 1 of a 21 day cycle

Treatment

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or their parent(s)/legal guardian(s) has provided written informed consent using the main study PICF
• Male or female patient, aged 2 years or older
• Patient has pathologically confirmed locally advanced, incurable or metastatic cancer of any histological type
• Have an available TRIAGE sub-study with a matched therapy
• Documented progression following standard therapy, or for whom, in the opinion of the Investigator, no appropriate standard therapy exists
• Life expectancy of \> 3 months
• Adequate performance status:
• i. For patients aged 18 years or over, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (appendix 1) ii. For patients aged 17 years, Karnofsky score ≥ 50 (appendix 2) iii. For patients aged 16 years or under, Lansky score ≥ 50 (appendix 3)
• Treatment regimen and schedule of assessments that has been approved by the TAILOR Study Committee
• Approved treatment is obtainable
• Patient has measurable disease or evaluable disease as defined by RECIST 1.1 (or RANO criteria for primary CNS cancers or the Cheson (IWG) revised response criteria for lymphomas)
• Patient must have adequate bone marrow, hepatic and renal function within 7 days prior to registration:
• ANC ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L (platelet count ≥ 50 x 109/L for haematological malignancy indications)
• ALT ≤ 2.5x ULN, unless liver metastases or invasion are present, in which case it must be ≤ 5x ULN

You may not qualify if:

• Significant cardiovascular disease
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Other co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol
• Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy, with the exception of alopecia.
• Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product(s) may be included (e.g. hearing loss, peripheral neuropathy)
• Symptomatic, or actively progressing CNS metastases (unless a primary brain tumour).Patients with a history of treated
• CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease per RECIST 1.1 must be present outside the CNS Metastases are limited to the cerebellum or the supratentorial region (i.e. no metastases to the midbrain, pons, medulla, or spinal cord) There is no clinical evidence of interim progression between completion of CNS-directed therapy and registration on the study (radiological re-assessment is not required) The patient has not received radiotherapy within 14 days prior to registration Anticonvulsant therapy at a stable dose is permitted
• History of leptomeningeal disease unless a primary brain tumour
• Known active infection including tuberculosis, HBV, HCV, or HIV. Patients with a past or resolved HBV infection (defined as the presence of HBcAb and absence of HBsAg) are eligible. Patients with a past or resolved HCV infection are eligible only if polymerase chain reaction is negative for HCV RNA

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Neoplasms

Interventions

trametinib; cobimetinib; binimetinib; Alpelisib; Vemurafenib; dabrafenib; encorafenib; palbociclib; olaparib; ribociclib; abemaciclib; talazoparib; Nivolumab; atezolizumab; pembrolizumab

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Stephen Luen, MBBS

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2021
• First Posted: March 17, 2021
• Study Start: September 23, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)