TT-10 for Advanced Cancer

(ADPORT-601 Trial)

Recruiting at 8 trial locations

Overseen By Desa Rae E Stanton-Pastore, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Portage Biotech

Must not be taking: Immunosuppressants, CYP3A4 inhibitors

Disqualifiers: Active CNS metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral drug, TT-10, for safety and effectiveness in people with severe cancers that did not improve with usual treatments. The goal is to determine a safe dosage and see if it can help control tumor growth.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you require certain drugs like strong inhibitors or inducers of specific enzymes, or drugs that modify stomach acid levels. It's best to discuss your current medications with the trial team.

What safety data exists for TT-10 in humans?

Targeted therapies (TTs) like TT-10 have been studied for safety in various conditions, including cancer. Some studies report adverse events (unwanted side effects) such as skin reactions and other toxicities, but the reporting of these events is often not detailed enough. It's important to discuss potential side effects with your doctor before participating in a trial. ^{1 2 3 4 5}

How is the drug TT-10 different from other cancer treatments?

TT-10 is a targeted therapy, which means it works by specifically attacking cancer cells with less harm to normal cells, unlike traditional chemotherapy. It is likely taken orally and has a unique side effect profile that is generally less severe than conventional chemotherapy. ^{1 6 7 8 9}

What data supports the effectiveness of the treatment TT-10 for advanced cancer?

The study on head and neck cancer patients showed that adding docetaxel to a treatment plan improved survival and reduced side effects, suggesting that similar drug combinations might be effective for other advanced cancers. ^{10 11 12 13 14}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors like oral, head and neck, kidney, prostate or lung cancer who've not responded to standard treatments can join. They must have a life expectancy over 3 months, good blood and organ function, and be able to consent. Some need accessible tumors for biopsies.

Inclusion Criteria

My liver is functioning well.

My kidney function is within normal ranges.

I have RCC, CRPC, or NSCLC, can't get standard treatment, and my tumor can be biopsied.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks.

I have a history of hepatitis C.

I have not had any cancer treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of TT-10, TT-4, or TT-10 + TT-4 to determine the maximum tolerated dose

28 days per cycle

Weekly visits for dose escalation monitoring

Expansion Phase

Participants are treated at the recommended phase 2 dose to further evaluate safety and efficacy

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• TT-10

Trial Overview The trial is testing TT-10's safety when taken orally by patients with certain advanced cancers. It aims to find the highest dose patients can tolerate without severe side effects (MTD) or the suggested dose for future Phase 2 trials (RP2D).

How Is the Trial Designed?

Group I: Cohort C: Dose Escalation Experimental Treatment 2 Interventions

Drugs: TT-10 + TT-4 - Dual Receptor Antagonists * Both drugs will be supplied in capsules for daily oral administration and administered separately. * One cycle is considered 28 days * Ascending Dose levels of both drugs are being explored and will be determined after safety review of Cohorts A and B

Group II: Cohort B: Dose Escalation Experimental Treatment 1 Intervention

Drug: TT-4 (A2B Receptor Antagonist) * Supplied in capsules for daily oral administration once a day (QD) * One cycle is considered 28 days * Ascending Dose levels are being explored * Dose Level 1 * Dose Level 2 * Dose Level 3\* * \*Additional dose levels or frequency may be explored, if appropriate based on emerging safety, PK or pharmacodynamic data

Group III: Cohort A: Dose Escalation Experimental Treatment 1 Intervention

Drug: TT-10 (A2A Receptor Antagonist) * Supplied in capsules for daily oral administration twice a day (BID) * One cycle is considered 28 days * Ascending Dose levels are being explored * Dose Level 1 * Dose Level 2 * Dose Level 3 * Dose Level 4\* \*Additional dose levels may be explored, if appropriate based on emerging safety, PK or pharmacodynamic data

Who Is Running the Clinical Trial?

Portage Biotech

Lead Sponsor

Trials

1

Recruited

90+

Tarus Therapeutics, Inc.

Industry Sponsor

Trials

2

Recruited

90+

Published Research Related to This Trial

In a phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

A new online toxicity registration strategy was developed for children and young adults treated under the Nordic/Baltic acute lymphoblastic leukaemia protocol, which streamlined the process and achieved a high compliance rate of 98.9% within 5 weeks.

This approach focuses on monitoring serious but rare adverse events, allowing for real-time toxicity profiles and early warnings for specific toxicities, which can enhance patient safety and inform treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complying with the European Clinical Trials directive while surviving the administrative pressure - an alternative approach to toxicity registration in a cancer trial. Frandsen, TL., Heyman, M., Abrahamsson, J., et al.[2019]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

Citations

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Advanced thyroid carcinoma: an experience of 385 cases. [2007]

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Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events of targeted therapies reported by patients with cancer treated in primary care. [2021]

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Outcomes of patients with metastatic renal cell carcinoma and end-stage renal disease receiving dialysis and targeted therapies: a single institution experience. [2022]

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Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series. [2020]

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Complying with the European Clinical Trials directive while surviving the administrative pressure - an alternative approach to toxicity registration in a cancer trial. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]

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Retrospective Analysis of Fifth-Line Targeted Therapy Efficacy in Patients with Metastatic Renal Cell Carcinoma. [2022]

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13. England pubmed.ncbi.nlm.nih.gov

Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis. [2023]

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Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis. [2022]