IMA910 Plus GM-CSF With Low-dose Cyclophosphamide Pre-treatment in Advanced Colorectal Carcinoma Patients Following a Successful 12 Week First-line Treatment With Oxaliplatin-based Chemotherapy (IMA910-101)

• Status: Completed
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is being conducted in order determine whether IMA910 as single agent with GM-CSF as adjuvant following pre-treatment with low-dose cyclophosphamide is safe and shows sufficient anti-tumour effectiveness in patients with advanced CRC to warrant further development. Secondary objectives of this study are investigation of immunological parameters and additional effectiveness endpoints. Furthermore, safety, immunological parameters and effectiveness of IMA910 as single agent with GM-CSF in combination with imiquimod following pre-treatment with low-dose cyclophosphamide will be investigated in a 2nd cohort of patients.

The regular study duration for individual patients in the 1st and 2nd cohort comprises regularly 18-42 days of screening (excluding HLA-typing), 33 weeks of treatment (16 vaccinations) and 4 weeks follow-up. Thus, the period between start of screening and end of trial is about 10 months per patient. Patients will be followed for response to subsequent treatments (chemotherapies with or without targeted agents) and survival every 2 months after EOS visit until death.

Patients in the 1st and 2nd cohort will be withdrawn from study treatment once a progress according to RECIST is noted. An enrolment plan for the first 6 patients included into the 1st cohort will be part of this study to ensure maximum safety of the study participants. The enrollment of the first 6 patients into the 2nd cohort will also follow an enrolment plan to ensure maximum safety.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: immatics Biotechnologies GmbH
• Treatments: Cyclophosphamide; Imiquimod; Molgramostim; Oxaliplatin; Sargramostim

Criteria

Inclusion criteria:

• Aged at least 18 years

• HLA type: HLA-A*02-positive

• Histologically confirmed colorectal adenocarcinoma (CRC)

• Radiological evidence (CT/MRI) of unresectable locally advanced and/or metastatic CRC prior to 12 week first-line oxaliplatin-based standard chemotherapy

• 12 week first-line chemotherapy with an oxaliplatin-based regimen according to an established standard protocol (e.g. FOLFOX or XELOX) administered at the following minimum dosages over this 12 week period: Oxaliplatin 400 mg/m2, Fluorouracil (5FU) 10.000 mg/m2 or Capecitabine 84.000 mg/m2 (a time window for application of first-line chemotherapy of +4 weeks is allowed)

• Response (CR, PR) or stabilization (SD) following a 12 week first-line oxaliplatin-based standard chemotherapy shown by radiological evidence (CT/MRI after last cycle of firstline oxaliplatin-based standard chemotherapy compared to CT/MRI taken before start of first-line oxaliplatin-based standard chemotherapy)

• Patients accept a chemotherapy-free interval under close observation (CT or MRI scans performed every 9 weeks)

• Maximum period between start of study treatment (Cyclophosphamide) and start of the last cycle of standard chemotherapy (= first day of last cycle of standard chemotherapy) is 42 days; minimum period is 18 days

• Karnofsky Performance Status ≥80%

• Able to understand the nature of the study and give written informed consent

• Willing and ability to comply with the study protocol for the duration of the study

Exclusion criteria:

• Any adjuvant systemic or local chemotherapy if ended ≤6 months before start of systemic first-line oxaliplatin-based standard chemotherapy

• Progressive disease during or at the end of 12 week systemic first-line oxaliplatin-based standard chemotherapy

• CT/MRI scans taken more than 9 weeks before start of first-line oxaliplatin-based standard chemotherapy

• Response to 12 week first-line oxaliplatin-based standard chemotherapy resulting in resectable disease; curative treatment intended

• Immunosuppressive therapy within 10 days before first vaccination e.g. corticosteroid treatment (inhalative corticosteroids for e.g. asthma are allowed)

• Radiotherapy during and/or following the 12 week first-line oxaliplatin-based standard chemotherapy (palliative radiotherapy for bone metastasis is allowed)

• Concurrent or prior participation in a clinical trial applying interventional procedures (e.g. application of investigational drugs, surgical interventions) within the last 30 days before Screening 2 = Visit B

• History of other malignant tumours within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ

• Presence of known brain metastasis on MRI or CT scans

• Current partial or complete bowel obstruction

• Patients with a history or evidence of systemic autoimmune disease

• Any vaccination within 2 weeks before first vaccination

• Any planned prophylactic vaccination from study entry until the end of the induction period (Week 6 after first vaccination, exception: if medically indicated)

• Major surgery ≤4 weeks before first vaccination

• Any of the following abnormal laboratory values:

• Haematology:

• Hb <9 g/dL

• WBC <2.5 x 109/L

• Neutrophils <1.5 x 109/L

• Lymphocytes <1.0 x 109/L

• Platelets <75 x 109/L

• Liver function:

• Serum bilirubin >1.5 x upper normal limit (unless a history of Gilbert's disease)

• ALAT or ASAT >3 x upper normal limit (>5 x ULN if liver metastases are present)

• Alkaline Phosphatase >3 x upper normal limit (>5 x ULN if liver metastases are present)

• Renal function: serum creatinine >200 μmol/L (2.3 mg/dL)

• Known active hepatitis B or C infection

• Known HIV infection

• Active infections requiring oral or intravenous antibiotics

• Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues. Examples are: rabies, Mycobacterium tuberculosis, Coccidioides immitis

• Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, including gastrointestinal, hepatic, renal, respiratory, cardiovascular, haematological, coagulation, metabolic or hormonal diseases with clinically relevant abnormal organ function for example:

• Heart failure or non-compensated active heart disease (=NYHA Class III and IV)

• Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension

• Symptomatic neurotoxicity (motor or sensory) = Grade 3 according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE)

• Severe pulmonary dysfunction

• Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator's opinion

• Pregnancy or breast-feeding

• Hypersensitivity to the study drugs (cyclophosphamide, GM-CSF, IMA910) including excipients