Reduced-Dose Chemotherapy for Lung Cancer

Overseen By Ryan Romasko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must be taking: Cytotoxic agents

Must not be taking: Targeted agents, Immunotherapy

Disqualifiers: Gastrointestinal obstruction, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: First four cycles with dose modifications

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if reduced-dose chemotherapy remains effective and safe for people with lung cancer who also have other health issues. The study will test various chemotherapy drugs, such as Carboplatin, Docetaxel, Gemcitabine, Irinotecan, Lurbinectedin, Nab paclitaxel, Paclitaxel, Pemetrexed, and Topotecan, sometimes combined with immunotherapy or a VEGF inhibitor (a drug that helps stop the growth of blood vessels in tumors). It targets individuals with advanced lung cancer who have undergone other treatments but may not be suitable for standard full-dose chemotherapy. Those living with stage IV lung cancer and who have received prior treatment might find this trial suitable. As a Phase 2 trial, it focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, stable doses of anti-seizure medications are allowed if your CNS disease is treated and stable. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the chemotherapy drugs under study have different safety profiles. Here's a simple overview:

**Carboplatin**: Studies indicate that carboplatin resembles cisplatin, another common chemotherapy drug. It is usually well-tolerated, though some patients experience side effects like nausea or low blood cell counts.

**Docetaxel**: This drug can cause serious side effects. In studies, about 42% of patients experienced severe side effects, including lung and blood issues.

**Gemcitabine**: Research suggests that gemcitabine is generally well-tolerated and has a good safety profile. It shows promise for treating non-small cell lung cancer with manageable side effects.

**Irinotecan**: While effective, irinotecan often causes adverse effects, with serious outcomes in about 38% of patients and hospitalizations in roughly 30%.

**Lurbinectedin**: This drug has an acceptable safety profile. It is mainly used for small cell lung cancer, with manageable side effects.

**Nab-paclitaxel**: Findings show that nab-paclitaxel is generally safe, with acceptable side effects. It has improved outcomes in advanced lung cancer.

**Paclitaxel**: This drug is known for being safe and effective, with manageable side effects when used in certain doses.

**Pemetrexed**: Pemetrexed is considered relatively safe, even for patients with kidney issues. It is effective against certain types of lung cancer with minimal side effects.

**Topotecan**: Research suggests topotecan is effective and well-tolerated, especially in small cell lung cancer. Most side effects are manageable.

In summary, each drug has its own safety considerations, but many are well-tolerated with manageable side effects for most patients. Always discuss potential side effects with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore reduced-dose chemotherapy options for lung cancer, potentially minimizing side effects while maintaining effectiveness. Unlike traditional standard-of-care regimens that often involve full-dose combinations, this trial is investigating the effects of reduced doses, which could offer a better quality of life for patients. Additionally, the combination with immunotherapy and VEGF inhibitors (VEGFi) could enhance the body's own immune response to cancer, offering a new dimension in treatment. This approach not only aims to target the cancer cells more precisely but also to reduce the overall toxicity typically associated with chemotherapy.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that carboplatin, often used with other drugs, effectively treats lung cancer. In this trial, participants may receive carboplatin as part of a platinum doublet regimen, which can combine with nab-paclitaxel to improve survival rates. Docetaxel, another treatment option in this trial, shows promise, with some studies reporting survival times of up to 10.9 months. Gemcitabine, which participants might receive as a single agent, has demonstrated a response rate of over 20%, with survival times around 8-9 months when used alone. Irinotecan proves effective, especially in later treatment stages, with many patients completing several treatment cycles. Lurbinectedin, another potential treatment in this trial, has shown a response rate of about 20% when used as a second treatment option. Nab-paclitaxel, when combined with carboplatin, improves response rates and survival. Paclitaxel, in its various forms, has shown survival times of up to 14.3 months in some cases. Pemetrexed is particularly effective for non-squamous non-small cell lung cancer, with high response and control rates. Lastly, topotecan has effectively treated relapsed small-cell lung cancer, with some patients experiencing tumor shrinkage. This trial evaluates each treatment for its effectiveness in improving survival or response rates in lung cancer patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Julia Judd, DO

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage IV lung cancer (small cell or non-small cell) or inoperable stage III. They may have had previous treatments and can have stable, treated brain metastases. Participants must be able to perform daily activities (ECOG 0-3), not be pregnant, agree to use contraception, and plan to receive one of the listed chemotherapy drugs.

Inclusion Criteria

I am older than 18 years.

I am a man who will use birth control during and 6 months after the study.

I have brain metastases but don't need steroids, had no recent brain radiation, and if on seizure meds, my condition is stable.

Exclusion Criteria

I have another cancer, but it won't affect this trial's treatment.

Pregnant or breast feeding.

My cancer has spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dose attenuated chemotherapy regimens based on their comorbidities and age

First four cycles with dose modifications

Regular visits as per chemotherapy cycle schedule

Follow-up

Participants are monitored for safety, efficacy, and progression-free survival

6 years

Open-label extension (optional)

Participants may continue to receive treatment and be monitored long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Docetaxel
• Gemcitabine
• Irinotecan
• Lurbinectedin
• Nab paclitaxel
• Paclitaxel
• Pemetrexed
• Topotecan

Trial Overview The study tests lower doses of common chemotherapy drugs like Carboplatin and Paclitaxel in patients with other health issues. It's an open-label phase II trial, meaning everyone gets treatment and researchers know what's given. The goal is to see how well patients tolerate these reduced doses while monitoring effectiveness.

How Is the Trial Designed?

Group I: Single agent chemotherapy with or without a VEGFi Experimental Treatment 10 Interventions

Group II: Platinum doublet with or without a VEGFi Experimental Treatment 10 Interventions

Group III: Platinum doublet plus immunotherapy (IO) Experimental Treatment 10 Interventions

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving multiple patients.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: Trial data and implications for clinical management. Belani, C., Lynch, T.[2019]

In a series of studies involving patients with lung cancer, low-dose carboplatin combined with escalating doses of paclitaxel was tested to determine the maximum tolerated dose, with a maximum tolerated dose of 135 mg/m2 for paclitaxel in patients who had prior chemotherapy, where febrile neutropenia was the main side effect.

Among 21 evaluable patients treated with paclitaxel doses ranging from 100 to 270 mg/m2, there were two partial responses, one minor response, and ten patients with stable disease, indicating some efficacy of the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase studies with paclitaxel/low-dose carboplatin in patients with solid tumors. Creaven, PJ., Raghavan, D., Perez, RP., et al.[2015]

A combination treatment of paclitaxel, carboplatin, and oral etoposide was found to be highly effective and well tolerated in 117 patients with small-cell lung cancer, showing promising results in both extensive and limited stages of the disease.

The regimen can be safely administered alongside thoracic radiation therapy, with only a few patients experiencing esophagitis, indicating a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Hainsworth, JD., Hopkins, LG., Thomas, M., et al.[2015]

The combination of docetaxel and gemcitabine has shown promising efficacy in treating previously untreated patients with advanced non-small cell lung cancer, achieving response rates between 25% to 50% and a median survival of 11 to 13 months, while being well tolerated with reduced neutropenia risk in weekly schedules.

Docetaxel combinations with vinorelbine and irinotecan also demonstrated comparable efficacy, with one-year survival rates of 60% and 55% respectively, suggesting these combinations could serve as effective alternatives to traditional platinum-based chemotherapy, warranting further phase III evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenging the platinum combinations in the chemotherapy of NSCLC. Douillard, JY., Eckardt, J., Scagliotti, GV.[2022]

The combination of docetaxel and cisplatin showed a response rate of 32% and a median survival of 11.5 months in patients with advanced non-small-cell lung cancer (NSCLC), indicating its efficacy as a treatment option.

When combined with carboplatin, docetaxel demonstrated an improved response rate of 36% and a longer median survival of 13.9 months, suggesting that this combination may have a better safety profile and therapeutic index compared to the cisplatin combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in combination with platinum compounds for non small-cell lung cancer. Belani, CP.[2019]

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving various patient populations.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management. Belani, C., Lynch, T.[2018]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

The combination of docetaxel and cisplatin is effective for treating stage IIIB/IV non-small cell lung cancer, showing response rates between 32% and 48% and median survival times of 8 to 13 months across four phase II trials.

Docetaxel combined with carboplatin also demonstrated promising results, with a 48% response rate in a small group of 27 patients, indicating that these combinations are well tolerated and may improve outcomes if used earlier in the disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinum-based regimens in non-small cell lung cancer: results and future developments. Belani, CP.[2018]

Docetaxel is an effective treatment for locoregionally advanced non-small cell lung cancer, showing promising results when used alone or in combination with platinum compounds and radiotherapy, with manageable side effects.

Phase I trials suggest that a regimen of weekly docetaxel and cisplatin or carboplatin combined with radiotherapy is suitable for further investigation, with predominant toxicities being esophagitis and neutropenia, but low rates of pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based combined-modality chemoradiotherapy for locally advanced non-small cell lung cancer. Scagliotti, GV., Turrisi, AT.[2019]

In a phase II trial involving 120 patients with extensive-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed a significantly higher overall response rate of 78% compared to 48% for the paclitaxel and topotecan combination.

The paclitaxel-carboplatin-etoposide regimen also resulted in a longer median time to progression (7.6 months) compared to the paclitaxel-topotecan group (5.5 months), indicating it may be a more effective initial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial. Greco, FA., Thompson, DS., Morrissey, LH., et al.[2015]

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

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