Palbociclib + Chemotherapy for Solid Tumors

Not currently recruiting at 157 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Must not be taking: Strong CYP3A inhibitors, Strong UGT1A1 inhibitors

Disqualifiers: Brain tumors, Cardiac disease, Infections, 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: 21

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining palbociclib, a cancer drug, with chemotherapy to treat solid tumors that have returned or are difficult to treat. The researchers aim to determine how well this combination works for specific cancers, such as neuroblastoma and Ewing sarcoma, in children, teens, and young adults. Participants must have a solid tumor diagnosis that has either returned or is not responding to treatment, like Ewing sarcoma or neuroblastoma. The trial seeks to find the best dosage and assess whether the new combination outperforms current treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use strong CYP3A inhibitors or inducers, or strong UGT1A1 inhibitors within 12 days of starting the study. It's best to discuss your current medications with the study team.

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

Research has shown that palbociclib, when combined with other chemotherapy drugs, is under careful study for safety in treating solid tumors in children, teens, and young adults. In studies, the combination of palbociclib and topotecan was generally well-tolerated, though some serious side effects occurred, including one death among seven participants. This indicates that while the treatment has potential, it also carries risks that must be considered.

For the combination of palbociclib, irinotecan, and temozolomide, research found that adding palbociclib did not significantly improve outcomes. The safety data suggested that this combination might not offer a favorable balance between benefits and risks. Some side effects were noted, though details are not provided.

Overall, these findings suggest that while palbociclib combinations can be tolerated, they come with potential risks. Participants should weigh these risks against potential benefits and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of palbociclib with chemotherapy for treating solid tumors like neuroblastoma because it offers a new approach to target cancer cells. Unlike traditional treatments that mainly focus on killing rapidly dividing cells, palbociclib specifically inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cancer cell proliferation. This targeted mechanism could potentially enhance the effectiveness of chemotherapy agents like topotecan, cyclophosphamide, irinotecan, and temozolomide, making the treatment more powerful against stubborn tumors. By potentially reducing the cancer cells' ability to repair and multiply, these combinations might offer a more effective and less toxic treatment option.

What evidence suggests that this trial's treatments could be effective for recurrent or refractory solid tumors?

Research has shown that palbociclib, when combined with chemotherapy, may help treat certain solid tumors. In this trial, one treatment arm evaluates palbociclib with topotecan and cyclophosphamide, which studies suggest may be more effective for neuroblastoma. Another arm assesses adding palbociclib to irinotecan and temozolomide for Ewing sarcoma, potentially improving outcomes compared to chemotherapy alone. These combinations may be effective because palbociclib targets cancer cell growth, enhancing chemotherapy's impact. Early evidence suggests this method could help control tumor growth in challenging cases. ^{1 2 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 2-21 with relapsed or refractory solid tumors, including specific types like Ewing sarcoma. They must have a certain level of physical ability, adequate organ function, measurable disease, and not be pregnant. Those with severe allergies to the drugs used or serious health issues are excluded.

Inclusion Criteria

My cancer has returned or didn't respond to treatment, as confirmed by a lab test.

My liver is working well.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

I haven't taken strong CYP3A affecting drugs recently.

Prior intolerability to specified treatments

Severe acute or chronic medical or laboratory abnormalities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Phase 1: Participants receive palbociclib in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) to determine the maximum tolerable dose. Phase 2: Participants receive palbociclib in combination with irinotecan and temozolomide or irinotecan and temozolomide alone for efficacy evaluation.

12 weeks

Multiple visits per cycle (each cycle is 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and laboratory abnormalities.

At least 28 days after last dose

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Irinotecan
• Palbociclib
• Temozolomide
• Topotecan

Trial Overview The study tests Palbociclib combined with chemotherapy (Temozolomide/Irinotecan or Topotecan/Cyclophosphamide) to find the safest high dose in phase 1 and its effectiveness compared to just chemo in phase 2 for Ewing sarcoma.

How Is the Trial Designed?

Group I: Phase 2 Arm A Experimental Treatment 3 Interventions

Palbociclib in combination with irinotecan and temozolomide.

Group II: Phase 1 Tumor specific cohort - Neuroblastoma Experimental Treatment 3 Interventions

Palbociclib in combination with topotecan and cyclophosphamide.

Group III: Phase 1 Experimental Treatment 5 Interventions

Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.

Group IV: Phase 2 Arm B Active Control 2 Interventions

Irinotecan and temozolomide alone.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Children's Oncology Group (COG)

Collaborator

Trials

3

Recruited

380+

Published Research Related to This Trial

Irinotecan, a derivative of camptothecin, has shown significant activity against recurrent malignant glioma in clinical trials, confirming its potential as a treatment option for this aggressive brain tumor.

Combining irinotecan with alkylating agents like BCNU or temozolomide enhances its antitumor effects, leading to ongoing Phase II trials to evaluate these combinations in adults with malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Friedman, HS., Keir, ST., Houghton, PJ.[2018]

Temozolomide is a promising drug for combination therapies due to its ability to cross the blood-brain barrier, good safety profile, and effectiveness against solid tumors like malignant glioma, especially when combined with carmustine or irinotecan.

Studies indicate that administering carmustine before temozolomide results in lower toxicity and a higher maximum tolerated dose, while the combination of temozolomide followed by irinotecan shows greater effectiveness than either drug alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with other cytotoxic agents. Prados, M.[2019]

In a study of 117 patients with clear cell carcinoma of the ovary, the combination of irinotecan hydrochloride and cisplatin (CPT-P) showed a progression-free survival (PFS) rate of 55% at 5 years, suggesting it may be an effective treatment option.

While the CPT-P regimen did not show a statistically significant survival advantage over the standard paclitaxel and carboplatin (TC) treatment, it demonstrated comparable efficacy, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis. Takano, M., Sugiyama, T., Yaegashi, N., et al.[2018]

The TMZ-resistant glioma cell line SF188/TR showed a 6-fold resistance to temozolomide and cross-resistance to various other anticancer agents, indicating a significant challenge in treating resistant tumors.

Increased activity of the enzyme alkylguanine alkyltransferase (AGT) was identified as a primary mechanism of resistance to TMZ, while changes in the balance of pro-apoptotic and anti-apoptotic proteins contributed to broader cross-resistance to other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Ma, J., Murphy, M., O'Dwyer, PJ., et al.[2022]

In a study involving 107 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of irinotecan (CPT-11) was found to be 325 mg/m² for those taking enzyme-inducing anticonvulsants and 125 mg/m² for those not taking them, indicating significant variability in tolerance based on concurrent medications.

The combination of CPT-11 and temozolomide (TMZ) resulted in a 14% radiographic response rate, with patients showing a median time to disease progression of 54.9 weeks, suggesting that this treatment regimen may be effective for recurrent glioblastoma multiforme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. Reardon, DA., Quinn, JA., Rich, JN., et al.[2022]

Citations

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Study Of Palbociclib Combined With Chemotherapy In ... A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with ...

2. fda.gov fda.gov/media/188805/download?attachment

Ibrance (palbociclib) Written Request Study 1: An open-label, dose-escalation and cohort expansion study to evaluate the safety, pharmacokinetics (PK) and antitumor activity of palbociclib in ...

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03709680/

Clinical Trial: NCT03709680 The main purpose of this study is to evaluate the safety of palbociclib in combination with chemotherapy in order to estimate the maximum ...

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Labeling Supplement – Clinical Review APEC1621I was a single arm, Phase 2 study of palbociclib in children with r/r advanced solid tumors harboring activating alterations in cell ...

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NCT03709680 | Study Of Palbociclib Combined With ... A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS11583

Phase 2 study to evaluate palbociclib in combination with ... The primary objective of this portion of the study is to determine whether the addition of palbociclib to irinotecan (IRN) and temozolomide (TMZ) will prolong ...

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Phase 1 Study to Evaluate the safety and pharmacokinetics ... Phase 1 Study to Evaluate the safety and pharmacokinetics of palbociclib in combination with irinotecan and temozolomide in pediatric patients with recurrent or ...

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Ibrance, INN-palbociclib - Assessment report - EMA The final data from study A5481092 does not support a positive benefit risk for the addition of palbociclib to the combination of irinotecan and temozolomide in ...