What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy agents like etoposide and platinum-based drugs, which often cause side effects such as nausea, vomiting, hair loss, and myelosuppression. Mycophenolate Mofetil, an immunosuppressant, can lead to gastrointestinal distress, increased infection risk, and hematologic abnormalities. Allopurinol, used to manage uric acid levels, may cause skin rashes, gastrointestinal issues, and rare severe hypersensitivity reactions. Immune checkpoint inhibitors can result in immune-related adverse effects like colitis, pneumonitis, and endocrinopathies.

What prior FDA approvals exist?

FDA-approved treatments for Small Cell Lung Cancer (SCLC) primarily include chemotherapy regimens such as etoposide combined with platinum-based drugs (cisplatin or carboplatin). Recently, immune checkpoint inhibitors like atezolizumab (anti-PD-L1) have been approved for use in combination with chemotherapy in extensive-stage SCLC. While Mycophenolate Mofetil and Allopurinol are not standard treatments for SCLC, the CLAMP trial is investigating their potential to improve outcomes when added to chemotherapy. These drugs have different mechanisms of action, with Mycophenolate Mofetil reducing lymphocyte proliferation and Allopurinol reducing uric acid production, which may offer novel therapeutic benefits in combination with traditional chemotherapy.

What other types of research exist?

Promising novel alternatives for Small Cell Lung Cancer (SCLC) patients in 2024 include immune checkpoint inhibitors such as pembrolizumab and nivolumab, which have shown efficacy in enhancing the immune response against cancer cells. Additionally, targeted therapies like lurbinectedin, which has been approved for relapsed SCLC, and novel agents like Rova-T (rovalpituzumab tesirine), an antibody-drug conjugate targeting DLL3, are also promising. These treatments focus on specific molecular targets and mechanisms, offering potential benefits over traditional therapies.

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Alkylating agents

Chemotherapy + Allopurinol + Mycophenolate for Small Cell Lung Cancer

Phase 1

Waitlist Available

Led By Siddhartha Devarakonda, MBBS, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG performance status ≤ 2

At least 18 years of age

Must not have

Active hepatitis C

Presence of active infections or patients who are not candidates for immunosuppression with MMF

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through 6 months after completion of treatment (estimated to be 10 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if adding MMF and allopurinol to chemotherapy can help patients with relapsed small cell lung cancer by improving their response to treatment and delaying cancer progression.

Who is the study for?

This trial is for adults with small cell lung cancer that's come back after platinum-based chemo and anti-PD-L1 therapy. They must have measurable disease, be able to perform daily activities (ECOG ≤ 2), and have normal organ function. Participants need to use contraception and can't join if they've had certain infections or treatments recently, other cancers, intolerances to specific drugs, active autoimmune diseases, HIV/AIDS, hepatitis B/C, brain metastases requiring treatment or are pregnant/breastfeeding.

What is being tested?

The CLAMP Trial tests whether adding mycophenolate mofetil (MMF) and allopurinol to the chemotherapy drug irinotecan improves outcomes for relapsed small cell lung cancer patients. It aims to see if this combination is safe and increases the time without disease progression compared to past single-agent chemotherapies.

What are the potential side effects?

Possible side effects include immune system suppression leading to increased infection risk; gastrointestinal issues like nausea or diarrhea; liver problems; potential first trimester pregnancy loss or birth defects if taken during pregnancy; allergic reactions similar in nature to those caused by MMF or allopurinol.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself but might not be able to do heavy physical work.

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I am 18 years old or older.

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My small cell lung cancer worsened after treatment with platinum-based chemo and anti-PD-L1.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have active hepatitis C.

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I do not have active infections and can receive immunosuppressive treatment.

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I haven't taken any antibiotics by mouth or IV in the last 2 weeks.

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I am on medication for a chronic diarrheal illness like IBD.

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I have a significant liver condition.

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I have active tuberculosis.

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I am not taking any strong CYP3A4 inducers or inhibitors.

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I do not have symptoms from brain metastases.

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I am allergic to medications similar to MMF, allopurinol, or others used in this study.

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I have lung inflammation needing treatment or extra oxygen.

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I have active hepatitis B.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through 6 months after completion of treatment (estimated to be 10 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through 6 months after completion of treatment (estimated to be 10 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through 6 months after completion of treatment (estimated to be 10 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response rate (ORR) (Phase II and phase I patients who receive the MTD)

Recommended phase II dose (RP2D) (Phase I only)

Secondary study objectives

Overall survival (OS) (Phase II and phase I patients who receive the MTD)

Progression-free survival (PFS) (Phase II and phase I patients who receive the MTD)

Side effects data

From 2014 Phase 3 trial • 87 Patients • NCT00075478

23%

Blood/Bone marrow

11%

Cardiovascular

Pulmonary

Gastrointestinal

Hepatic

Graft versus host disease with infection and organ failure

Dermatology/Skin

respiratory failure

Hemorrhage

subdural hematoma

thrombosis

Renal/Genitourinary

Metabolic/Laboratory

100%

80%

60%

40%

20%

Study treatment Arm

Arm II (TBI, Transplant, GVHD Prophylaxis)

Arm I (Chemotherapy, TBI, Transplant, GVHD Prophylaxis)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase II: MMF + Irinotecan + AllopurinolExperimental Treatment3 Interventions

-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at the assigned dose level on Days 1 and 8. Cycles are 21 days.

Group II: Phase I Dose Level 1a: MMF + Irinotecan + AllopurinolExperimental Treatment3 Interventions

Group III: Phase I Dose Level 1: MMF + Irinotecan + AllopurinolExperimental Treatment3 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mycophenolate Mofetil

1997

Completed Phase 4

~2380

Allopurinol

1999

Completed Phase 4

~6150

Irinotecan

2017

Completed Phase 3

~2590

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy, immunotherapy, and targeted therapies. Chemotherapy, often using agents like etoposide and platinum compounds, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Immunotherapy, such as anti-PD-1 or anti-PD-L1 antibodies, enhances the body's immune response against cancer cells by blocking inhibitory signals that prevent immune cells from attacking tumors. Targeted therapies, like mTOR inhibitors, disrupt specific molecular pathways critical for cancer cell survival and proliferation. Mycophenolate Mofetil, which inhibits inosine monophosphate dehydrogenase, and Allopurinol, which inhibits xanthine oxidase, are being studied for their potential to improve outcomes in SCLC by reducing lymphocyte proliferation and uric acid production, respectively. These mechanisms are crucial for SCLC patients as they offer multiple avenues to hinder cancer progression and improve survival rates.

Combinations of 5-FU, hypoxanthine and allopurinol in chemotherapy for human colon adenocarcinoma xenografts.The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620.Ethanolic Extracts from Azadirachta indica Leaves Modulate Transcriptional Levels of Hormone Receptor Variant in Breast Cancer Cell Lines.