Targeted Therapy for Advanced Rare Cancers

(PREDiCTc Trial)

Overseen By Samantha Pollard, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Must be taking: Targeted therapy

Disqualifiers: Other trials, Unfit, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot clinical trial aims to assess the real world quality of life and survival of patients treated with targeted therapy that has preliminary evidence of efficacy in subjects with advanced rare cancers or cancer harbouring rare molecular aberrations. The treatment has been granted conditional or full approved by Health Canada (HC) as effective and safe. Due to the rarity of the cancer or molecular aberration the uncertainty level of the health technology assessment (HTA) by the pan Canadian Oncology Review (pCODR) was too high for consideration of funding or it was not submitted for consideration. Consequently, the goal of this study is to generate real world evidence to support HTA decision making throughout the life cycle of the product.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you are currently receiving a specific targeted therapy approved by Health Canada. You cannot participate if you've been treated with another agent or in another trial within 14 days before joining this one.

What data supports the effectiveness of the targeted therapy for advanced rare cancers?

Research shows that using targeted therapies based on specific genetic changes in rare cancers can be beneficial. In one study, 38% of patients with rare tumors had genetic changes that could be targeted with specific drugs, and some patients experienced positive responses, such as tumor shrinkage or stable disease. ^{1 2 3 4 5}

What safety data exists for targeted therapies in humans?

The safety of targeted therapies has been evaluated in various clinical trials, including umbrella trials in precision oncology, which assess the risk and benefit of these treatments. These studies suggest that targeted therapies can be safely administered to patients with advanced cancers, although specific safety profiles may vary depending on the genetic changes within the tumors. ^{3 6 7 8 9}

How is targeted therapy different from other treatments for advanced rare cancers?

Targeted therapy for advanced rare cancers is unique because it uses precision medicine to identify and attack specific genetic changes in cancer cells, offering a personalized treatment option where standard treatments often don't exist. This approach can lead to better outcomes by focusing on the unique genetic makeup of each patient's cancer. ^{1 2 3 10 11}

Research Team

Cheryl Ho, MD

Principal Investigator

BC Cancer

Eligibility Criteria

This trial is for adults over 18 with advanced rare cancers or those with uncommon molecular changes, who are expected to live at least 12 weeks. They must be on a Health Canada approved targeted therapy not covered by national funding, have stable brain metastases if present, and be physically able to undergo treatment (ECOG 0-2). Participants need functioning major organs and the ability to consent.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

I am able to care for myself and move around.

I have brain metastases that are either symptom-free or treated.

Exclusion Criteria

My doctor thinks I am not fit for this treatment plan.

Inability to complete quality of life questionnaires

I haven't taken any experimental drugs or joined another clinical trial in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive targeted therapy for advanced rare cancers or cancers with rare molecular aberrations

12 weeks

Regular interval radiographic imaging and collection of patient-reported outcomes

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Targeted Therapy

Trial Overview The PREDiCTc trial is evaluating the quality of life and survival rates in patients using targeted therapies for rare cancers. These treatments have some evidence of working but aren't widely funded due to their novelty. The study uses CT imaging and Quality of Life (QOL) assessments as tools.

Participant Groups

Group I: Targeted therapy Experimental Treatment 2 Interventions

Targeted Therapy is already approved in Canada, European Union, United States for the following indications:

Approved in Canada as Targeted Therapy for:

• Advanced rare cancers
• Cancer harbouring rare molecular aberrations

Approved in European Union as Targeted Therapy for:

• Various cancers with specific molecular targets

Approved in United States as Targeted Therapy for:

• Specific cancers with FDA-approved targeted therapies

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Findings from Research

Rare cancers, such as bone and soft-tissue sarcomas and neuroendocrine tumors, represent about 25% of all cancers but are often under-researched, leading to limited treatment options and poorer prognoses for patients.

Recent advancements in molecular analyses and innovative imaging techniques are enhancing the diagnosis and treatment of these rare cancers, emphasizing the need for multidisciplinary collaboration and the establishment of dedicated reference centers to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology-guided precision medicine in rare cancers: Lessons from sarcomas and neuroendocrine tumours. van der Graaf, WTA., Tesselaar, MET., McVeigh, TP., et al.[2022]

In a study of 95 patients with rare tumors, genomic profiling identified actionable mutations in 38% of cases, suggesting that targeted therapies could be beneficial for these patients.

Notably, tumors with BRAF mutations showed positive responses to BRAF inhibitors, indicating that genomic profiling can provide new treatment options for rare cancers that lack standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers. Groisberg, R., Hong, DS., Roszik, J., et al.[2020]

The TAPUR Study is a large-scale clinical trial involving over 1000 participants with advanced cancer, aiming to evaluate the effectiveness of FDA-approved drugs matched to specific genomic targets, showing promising preliminary activity in 12 out of 16 cohorts.

The study's primary goal is to assess the objective response or stable disease for at least 16 weeks, while also monitoring safety and overall survival, indicating a structured approach to personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Mangat, PK., Halabi, S., Bruinooge, SS., et al.[2022]

Rare cancers make up 22% of all cancer diagnoses, but patients with these cancers have poor median survival rates compared to those with common cancers.

To improve outcomes for rare cancer patients, it's essential to redesign clinical trial protocols and adopt new treatment paradigms that have been successful for more common cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial design for rare cancers: why a less conventional route may be required. Panageas, KS.[2018]

Molecular characterization of common cancers reveals they often consist of many rare genomic diseases, each driven by specific alterations that can be targeted for treatment.

Personalized medicine programs, which profile tumor samples to identify oncogenic drivers, show promise but currently yield modest anti-tumor effects due to challenges like identifying key drivers, tumor heterogeneity, and the complexity of genomic alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The genetic complexity of common cancers and the promise of personalized medicine: is there any hope? Arnedos, M., Vielh, P., Soria, JC., et al.[2022]

In a systematic review of 31 sub-trials involving 1637 cancer patients, the overall objective response rate (ORR) for therapies in umbrella trials was 17.7%, indicating that only about one in five patients responded positively to treatment.

The combination of targeted therapies with chemotherapy showed a significantly higher ORR of 39.0% compared to 13.3% for targeted therapies alone, but the overall drug-related death rate was low at 0.8%, suggesting that while umbrella trials may not guarantee increased benefits, they have a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis. Strzebonska, K., Blukacz, M., Wasylewski, MT., et al.[2023]

In a study of 1,310 patients with rare cancers, comprehensive molecular analysis using whole-genome/exome and RNA sequencing led to evidence-based management recommendations in 88% of cases, highlighting its potential to improve treatment strategies.

Patients who received recommended therapies based on molecular profiling showed significantly better outcomes, with overall response rates of 23.9% and disease control rates of 55.3%, indicating that molecular stratification can enhance treatment efficacy in this underserved population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Horak, P., Heining, C., Kreutzfeldt, S., et al.[2022]

In a study involving 500 patients, including 164 with rare cancers, it was found that patients with rare cancers can achieve a clinical benefit rate of 33% from approved anticancer drugs, similar to patients with more common cancers.

Patients with rare cancers showed particularly high clinical benefit rates (75%) when treated with small-molecule inhibitors targeting BRAF, indicating that comprehensive molecular testing can uncover effective treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment. Hoes, LR., van Berge Henegouwen, JM., van der Wijngaart, H., et al.[2023]

Comprehensive genomic profiling of rare tumors revealed a significantly higher prevalence of targetable genomic alterations (TGAs) in a Chinese cohort (53.43%) compared to a western cohort (20.40%), suggesting that patients in China may have more treatment options available.

Specific mutations, such as those in BRAF, BRCA2, and EGFR, were found to be over three times more frequent in the Chinese population, indicating that targeted therapies could be particularly effective for certain rare tumor types in this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies. Wang, S., Chen, R., Tang, Y., et al.[2020]

This phase II clinical trial aims to evaluate the safety and efficacy of targeted therapies and PD-1 inhibitors in patients with advanced rare solid tumors, involving a total of 770 participants who have failed standard treatments.

The study will assess the objective response rate as the primary endpoint, along with secondary endpoints like progression-free survival and adverse events, providing valuable insights into treatment options for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. Wang, S., Huang, HY., Wu, D., et al.[2021]

The MASTER precision oncology network shows that using whole-genome/exome and RNA sequencing can lead to targeted treatments for patients with advanced rare cancers, which are often poorly understood.

This approach has been beneficial for a significant number of patients, highlighting the potential for future clinical trials to further explore these personalized treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interdisciplinary team science to understand and intercept rare cancers. Fröhling, S.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Biology-guided precision medicine in rare cancers: Lessons from sarcomas and neuroendocrine tumours. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Clinical trial design for rare cancers: why a less conventional route may be required. [2018]

5. England pubmed.ncbi.nlm.nih.gov

The genetic complexity of common cancers and the promise of personalized medicine: is there any hope? [2022]

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

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies. [2020]

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

Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Interdisciplinary team science to understand and intercept rare cancers. [2022]